RPEP-02102 · 2012Intradermal injection of Substance P in normal rats induced mechanical allodynia (pain from light touch), warmth, edema, and upregulation of inflammatory mediators TNF-α, IL-1β, IL-6, and NGF in hindpaw skin. The NK1 receptor antagonist LY303870 attenuated allodynia, hindpaw unweighting, warmth, edema, cytokine expression, and epidermal thickening after fracture. Anti-NGF antibody blocked SP-induced pain but not warmth or edema, indicating NGF mediates the pain component specifically. LY303870 had no effect on bone microarchitecture, showing SP/NK1 signaling drives nociceptive and vascular but not skeletal components of CRPS.
Wei, Tzuping; Guo, Tian-Zhi; Li, Wen-Wu; Hou, Saiyun; Kingery, Wade S; Clark, John David ·
RPEP-02108 · 2012Self-assembled nanoparticles combining ε-oligo(L-lysine) peptides with the cationic lipid DOTAP and plasmid DNA achieved transfection efficiency that exceeded DOTAP alone, without a significant increase in cytotoxicity.
High transfection efficiency correlated with a zeta potential above +20 mV and a particle size below 500 nm. Synchrotron small-angle X-ray scattering confirmed the complexes formed ordered lamellar (layered) supramolecular structures, suggesting that the structural organization contributes to their gene-delivery performance.
Yan, Jiang; Korolev, Nikolay; Eom, Khee Dong; Tam, James P; Nordenskiöld, Lars ·
RPEP-02110 · 2012The Substance P gene Tac1 oscillates in dorsal root ganglion (DRG) neurons under transcriptional regulation by BMAL1:CLOCK clock gene heterodimers. This produces rhythmic Substance P protein expression in the spinal dorsal horn. Formalin-induced inflammatory pain responses in mice (n=48) followed the same circadian rhythm as Substance P expression. Blocking the SP-NK1R pathway (n=70) abolished the circadian pain rhythm. Clock gene deletion mutations disrupted both Substance P oscillation and behavioral pain rhythms, confirming the causal chain from peripheral clock → Substance P oscillation → circadian inflammatory pain.
Zhang, Jing; Li, Huili; Teng, Huajing; Zhang, Ting; Luo, Yonglun; Zhao, Mei; Li, Yun-Qing; Sun, Zhong Sheng ·
RPEP-02119 · 2013The review covers the ghrelin receptor GHS-R1a from discovery to therapeutic potential:
- GHS-R1a was expression-cloned at MERCK laboratories in the early 1990s using synthetic GH secretagogue molecules
- The receptor is expressed in the brain and throughout the body
- Its endogenous ligand, the peptide hormone ghrelin, regulates metabolism, neurotransmission, and behavior
- Multiple GHS-R1a agonists and antagonists are available, with some showing promising clinical results
- A second receptor form (GHS-R1b) also exists, though its function is less well characterized
- Rodent studies have revealed potential roles for receptor modulation in obesity, glucose homeostasis, and other conditions
Albarrán-Zeckler, Rosie G; Smith, Roy G ·
RPEP-02120 · 2013Using an intein-based expression system combined with parallel solid-phase synthesis, researchers generated an array of C-terminally modified PYY(3-36) analogues with substitutions at positions Arg33, Gln34, Arg35, and Tyr36.
Key findings from functional Y2 receptor assays:
- Substitutions at Tyr36 were generally better tolerated than modifications at Arg33, Gln34, or Arg35
- Arg33, Gln34, and Arg35 were critical for Y2 receptor activation
- Two analogues showed significantly improved Y2 receptor selectivity compared to native PYY(3-36)
- These results provide a foundation for designing new PYY-based obesity drug candidates with improved receptor selectivity
Albertsen, Louise; Østergaard, Søren; Paulsson, Johan F; Norrild, Jens Chr; Strømgaard, Kristian ·
RPEP-02129 · 2013Ghrelin influences multiple neuroendocrine axes: (1) It stimulates the HPA axis (stress response) independently of the pituitary, acting through the hypothalamus via CRH, AVP, and neuropeptide Y. (2) In ACTH-secreting tumors (Cushing's disease), pathological ghrelin receptor expression causes especially high ACTH and cortisol responses. (3) Ghrelin stimulates prolactin release from somatomammotroph cells. (4) Effects on thyroid axis regulation remain controversial. (5) Ghrelin inhibits FSH and especially LH secretion, likely through hypothalamic inhibition of GnRH.
Benso, Andrea; Calvi, Elisa; Gramaglia, Elena; Olivetti, Ilaria; Tomelini, Michela; Ghigo, Ezio; Broglio, Fabio ·
RPEP-02130 · 2013Elastin-derived peptides (EDPs) — fragments released when the structural protein elastin breaks down during aging — were found to directly cause insulin resistance in mice. When injected intravenously (either as a single dose or repeatedly), EDPs triggered hyperglycemia and reduced glucose uptake in skeletal muscle, liver, and adipose tissue. The mechanism involves EDPs activating the elastin receptor complex, whose neuraminidase-1 subunit then interacts with the insulin receptor. This interaction strips sialic acid residues from the insulin receptor's beta-chain, impairing its signaling cascade. This is the first study to show that elastin degradation products — which naturally accumulate as we age — can directly interfere with insulin signaling and promote insulin resistance.
Blaise, Sébastien; Romier, Béatrice; Kawecki, Charlotte; Ghirardi, Maxime; Rabenoelina, Fanja; Baud, Stéphanie; Duca, Laurent; Maurice, Pascal; Heinz, Andrea; Schmelzer, Christian E H; Tarpin, Michel; Martiny, Laurent; Garbar, Christian; Dauchez, Manuel; Debelle, Laurent; Durlach, Vincent ·
RPEP-02134 · 2013Using partial sciatic nerve ligation in gene-deficient mice:
- PACAP(-/-) mice: Did NOT develop mechanical hyperalgesia (30-40% in wildtype), identifying PACAP as crucial for neuropathic pain
- Tac1(-/-) mice (lacking SP/NKA): Developed hyperalgesia normally — tachykinins are NOT required for neuropathic pain
- Tacr1(-/-) mice (lacking NK1 receptor): Also developed hyperalgesia normally
- Motor coordination: Impaired in both PACAP(-/-) and Tac1(-/-) mice, unaffected in Tacr1(-/-)
- Basal skin blood flow: Reduced in Tac1(-/-) and Tacr1(-/-), normal in PACAP(-/-)
- Neurogenic vasodilation (mustard oil): Significantly reduced in PACAP(-/-), normal in Tac1(-/-) and Tacr1(-/-)
Conclusion: PACAP and tachykinins have distinct, non-overlapping roles in pain, vascular regulation, and motor function.
Botz, Bálint; Imreh, András; Sándor, Katalin; Elekes, Krisztián; Szolcsányi, János; Reglődi, Dóra; Quinn, John P; Stewart, James; Zimmer, Andreas; Hashimoto, Hitoshi; Helyes, Zsuzsanna ·
RPEP-02135 · 2013After ingestion of 30 g of isotope-labeled casein, 356 peptides were detected and sequenced in the jejunum over 6 hours, compared to 146 peptides from whey protein. β-casein was the dominant precursor of bioactive peptides.
Critically, β-casomorphins (β-casein fragments 57-66, with opioid activity) and β-casein 108-113 (with antihypertensive activity) were released at concentrations sufficient to elicit their known biological actions. Casein released medium-sized peptides (750-1050 kDa) continuously over 6 hours, while whey protein released larger peptides (1050-1800 kDa) primarily in the first 3 hours, reflecting their different digestive kinetics.
Boutrou, Rachel; Gaudichon, Claire; Dupont, Didier; Jardin, Julien; Airinei, Gheorghe; Marsset-Baglieri, Agnès; Benamouzig, Robert; Tomé, Daniel; Leonil, Joëlle ·
RPEP-02139 · 2013Enkephalin (ENK) mRNA expression was significantly lower in the basolateral amygdala of stress-vulnerable rats compared to both control and resilient rats, with no difference between resilient and control groups.
Dynorphin (DYN) mRNA was increased in the dorsal and medial shell of the nucleus accumbens only in vulnerable rats compared to controls. In contrast, DYN was increased in the central striatum (caudal part) specifically in resilient rats. Resilience was defined as average defeat latency >350 seconds over seven days of social defeat, while vulnerability was defined as <350 seconds.
Bérubé, Patrick; Laforest, Sylvie; Bhatnagar, Seema; Drolet, Guy ·
RPEP-02141 · 2013Ghrelin provided comprehensive cardioprotection during cardiopulmonary bypass in rats:
• Reduced inflammatory markers: TNF-α, IL-6, and myocardial myeloperoxidase activity were all decreased
• Reduced apoptosis (programmed cell death) in heart muscle cells
• Decreased oxidative stress in cardiac tissue
• Lowered levels of myocardial injury markers
• Significantly improved cardiac function after CPB
• In cultured cardiomyocytes, ghrelin increased cell viability and decreased apoptosis during simulated CPB
• Blocking the ghrelin receptor (with [D-Lys3]-GHRP-6) or the PI3K/Akt pathway (with wortmannin) eliminated all protective effects, confirming the mechanism involves GHSR-1a receptor activation and downstream Akt signaling
Cao, Yukun; Tang, Jun; Yang, Ting; Ma, Heng; Yi, Dinghua; Gu, Chunhu; Yu, Shiqiang ·
RPEP-02143 · 2013Neuropeptides like substance P drive inflammation through two distinct signaling waves: one at the cell surface and a second from inside the cell after the receptor is internalized into endosomes. Enzymes at each location control the intensity of these signals.
Deleting neprilysin (a surface enzyme that breaks down substance P) worsens inflammation because more pro-inflammatory peptide accumulates. Conversely, blocking ECE-1 (an enzyme inside endosomes) actually reduces inflammation by preventing receptors from recycling back to the surface for another round of signaling. β-arrestin proteins, which shuttle receptors into endosomes, also play a direct role in inflammatory cell migration and pro-inflammatory signaling.
Cattaruzza, Fiore; Poole, Daniel P; Bunnett, Nigel W · Review
RPEP-02144 · 2013All four cereal grains analyzed (wheat, oat, barley, and rice) contained high frequencies of ACE-inhibitor peptide sequences (occurrence frequencies A = 0.239 to 0.511), along with DPP-IV inhibitor, antithrombotic, antioxidant, hypotensive, and opioid peptide sequences. Wheat and rice proteins specifically contained anticancer sequences. Wheat and barley showed the greatest diversity and abundance of potential biological activity among the cereal proteins evaluated.
Cavazos, Ariel; Gonzalez de Mejia, Elvira ·
RPEP-02152 · 2013MSCs engineered to express VIP stopped disease progression and reduced symptoms in chronic EAE when given at peak disease. Improvements included decreased anti-MOG T cell responses, reduced CNS inflammation and demyelination, and preserved neuronal integrity. Neither VIP gene therapy alone nor unmodified MSCs were effective at peak disease — only the combination worked.
Cobo, Marién; Anderson, Per; Benabdellah, Karim; Toscano, Miguel G; Muñoz, Pilar; García-Pérez, Angélica; Gutierrez, Iván; Delgado, Mario; Martin, Francisco ·
RPEP-02153 · 2013Casein phosphopeptides (CPPs) — peptides produced when milk protein is digested — increase calcium uptake by intestinal cells, but this study found they do NOT work by modifying the molecular machinery for calcium absorption. Specifically, CPPs did not affect paracellular calcium transport (the pathway between cells), did not alter expression of the TRPV6 calcium channel, and did not change vitamin D receptor (VDR) expression in either HT-29 or Caco2 intestinal cell lines.
This means CPPs enhance calcium absorption through a different mechanism — likely by keeping calcium in a soluble form that cells can take up more easily, rather than by changing how cells transport calcium. Notably, the study also made a novel discovery: the TRPV6 calcium channel is expressed in HT-29 cells, the first time this had been demonstrated.
Colombini, Alessandra; Perego, Silvia; Ardoino, Ilaria; Marasco, Emiliano; Lombardi, Giovanni; Fiorilli, Amelia; Biganzoli, Elia; Tettamanti, Guido; Ferraretto, Anita · Basic Research
RPEP-02157 · 2013VIP (vasoactive intestinal peptide), a 28-amino-acid neuropeptide, functions far beyond its original discovery as a vasodilator. This review establishes VIP as a major immune regulator produced by both neurons and immune cells. VIP acts on macrophages, dendritic cells, and CD4+ T lymphocytes through specific receptors, modulating inflammatory and autoimmune responses.
The review covers VIP's involvement in inflammatory bowel disease, rheumatoid arthritis, multiple sclerosis, and other autoimmune conditions, as well as its current clinical applications and future therapeutic potential.
Delgado, Mario; Ganea, Doina · Review
RPEP-02167 · 2013When cerebrolysin was added to lymphocytes from CADASIL patients cultured under normal conditions, it had no effect on cell death rates. However, when cells were stressed with the pro-apoptotic agent 2-deoxy-D-ribose (dRib), cerebrolysin significantly decreased apoptosis after 48 hours — but only in 5 out of 15 patients (33%).
In the remaining 10 patients, cerebrolysin showed no protective effect against oxidative stress-induced cell death. The authors concluded that the Notch3 gene mutation in CADASIL probably does not influence cerebrolysin's anti-apoptotic properties, and that the variable response may reflect individual differences in disease biology.
Formichi, Patrizia; Radi, Elena; Battisti, Carla; Di Maio, Giuseppe; Dotti, Maria Teresa; Muresanu, Dafin; Federico, Antonio ·
RPEP-02170 · 2013Weight loss achieved with an intragastric balloon did not alter fasting levels of peptide YY (PYY) or adiponectin. Ghrelin increased while the balloon was in place (+39.3 pmol/L vs. baseline) but returned to baseline after removal (-34.7 pmol/L). Leptin decreased at 6 months (-11.7 ng/mL) but rebounded to baseline after balloon removal. Critically, no compensatory rise in ghrelin was observed in either group 12 months after initial weight loss, suggesting that this approach may avoid the hormonal rebound that typically drives weight regain after dieting.
Fuller, N R; Lau, N S; Denyer, G; Caterson, I D ·
RPEP-02172 · 2013Human GI enzyme digestion of bovine lactoferrin generated peptide fragments that differed substantially from those produced by non-human enzymes. Critically, bovine lactoferricin f(17-41) — the most well-characterized antimicrobial fragment — was not detected after either in vitro or in vivo human digestion. Degradation was highly pH-dependent: high gastric enzyme concentration with rapid pH reduction to 2.5 caused complete degradation, while slower pH reduction or higher pH preserved more intact lactoferrin. Proteolytic cutting sites were located on the protein surface, mainly on the non-glycosylated half. A proline-hydrophobic motif was identified that restricted proteolytic processing.
Furlund, C B; Ulleberg, E K; Devold, T G; Flengsrud, R; Jacobsen, M; Sekse, C; Holm, H; Vegarud, G E ·
RPEP-02175 · 2013Oral macimorelin achieved an area under the ROC curve of 0.96 for diagnosing adult GH deficiency, with 82% sensitivity and 92% specificity at a GH cutoff of 2.7 ng/mL. Peak GH levels differed dramatically between patients and controls: 2.36 ± 5.69 ng/mL in AGHD patients versus 17.71 ± 19.11 ng/mL in healthy controls (P < 0.001).
Obesity (BMI > 30 kg/m²), present in 58% of subjects, significantly affected results — peak GH levels were inversely correlated with BMI in controls (r = -0.37, P = 0.01). Using separate cutoffs of 6.8 ng/mL for non-obese and 2.7 ng/mL for obese subjects reduced the overall misclassification rate to 11%. The diagnostic accuracy was comparable to the arginine+GHRH test in the crossover portion of the study.
Garcia, J M; Swerdloff, R; Wang, C; Kyle, M; Kipnes, M; Biller, B M K; Cook, D; Yuen, K C J; Bonert, V; Dobs, A; Molitch, M E; Merriam, G R ·
RPEP-02181 · 2013Using zebrafish, researchers demonstrated that endogenous opioid peptides (Met-enkephalin, MEGY, and β-endorphin) regulate the expression of the μ-opioid receptor during brain development, and vice versa — creating a complex feedback loop. Knocking down the μ-opioid receptor gene disrupted normal brain development: dividing cells became disorganized in the optic tectum and mid/hindbrain, and cell death increased significantly in the CNS at 24 hours post-fertilization. Morphine administration also altered expression of the genes that produce endogenous opioid peptides (proenkephalins and proopiomelanocortin), revealing bidirectional regulation between exogenous opioids and the endogenous peptide system.
Gonzalez-Nunez, Veronica; Jimenez González, Ada; Barreto-Valer, Katherine; Rodríguez, Raquel E · Animal Study
RPEP-02185 · 2013Researchers built a machine learning tool called ToxinPred that predicts whether a peptide is toxic or non-toxic with 94.50% accuracy and a Matthews correlation coefficient (MCC) of 0.88. The model uses dipeptide composition — the frequency of all possible two-amino-acid combinations — as its primary feature set.
When tested on independent datasets (peptides not used during training), the model still achieved roughly 90% accuracy, indicating the results aren't just an artifact of overfitting. The team also found that certain amino acids — cysteine, histidine, asparagine, and proline — appear more frequently and at preferred positions in toxic peptides compared to non-toxic ones.
Beyond simple yes/no toxicity prediction, the tool can identify the minimum mutations needed to increase or decrease a peptide's toxicity and pinpoint toxic regions within larger proteins.
Gupta, Sudheer; Kapoor, Pallavi; Chaudhary, Kumardeep; Gautam, Ankur; Kumar, Rahul; Raghava, Gajendra P S · Computational
RPEP-02191 · 2013Compared to healthy controls, immune cells (PBMCs) from type 2 diabetes patients showed:
- Activated MAPK signaling pathways (P38, JNK, and ERK)
- Elevated superoxide anion (oxidative stress marker)
- Increased pro-inflammatory cytokines (TNF-α, IL-1β, IL-6)
- Increased chemokines (CCL5/RANTES and CXCL10/IP-10)
Exendin-4 treatment attenuated all of these inflammatory changes, likely through suppression of the p38 MAPK signaling pathway. This demonstrates that GLP-1 receptor agonists have direct anti-inflammatory effects on human immune cells, independent of their metabolic actions.
He, Lan; Wong, Chun Kwok; Cheung, Kitty Kt; Yau, Ho Chung; Fu, Anthony; Zhao, Hai-Lu; Leung, Karen Ml; Kong, Alice Ps; Wong, Gary Wk; Chan, Paul Ks; Xu, Gang; Chan, Juliana Cn ·
RPEP-02193 · 2013The six-amino-acid antimicrobial core of lactoferricin (LfcinB6, RRWQWR) was not cytotoxic to cancer cells on its own. Adding a hepta-arginine cell-penetrating sequence via a glycine-glycine linker created MPLfcinB6, which was selectively cytotoxic to human T-leukemia and B-lymphoma cells.
The killing mechanism involved extensive and irreparable cell membrane damage, confirmed by propidium iodide uptake, dextran uptake, and scanning electron microscopy. While the peptide also triggered ROS production and mitochondrial membrane permeabilization, neither ROS nor caspase activation was essential for cell death — membrane destruction was the primary killing mechanism.
Hilchie, Ashley L; Vale, Rachel; Zemlak, Tyler S; Hoskin, David W ·
RPEP-02195 · 2013The crystal structure of the human CRF1 receptor transmembrane domain was solved in complex with the small-molecule antagonist CP-376395. The structure revealed detailed atomic-level interactions between the receptor and the non-peptide ligand, which binds deep within the receptor's transmembrane helices.
This was the first transmembrane domain structure determined for any class B GPCR — a receptor family that was previously understood only from structures of its extracellular domain. The structure serves as a template for understanding the entire class B GPCR family, which includes receptors for many important peptide hormones (glucagon, GLP-1, PTH, calcitonin, and others).
Hollenstein, Kaspar; Kean, James; Bortolato, Andrea; Cheng, Robert K Y; Doré, Andrew S; Jazayeri, Ali; Cooke, Robert M; Weir, Malcolm; Marshall, Fiona H ·
RPEP-02196 · 2013GLP-1 is involved in both peripheral and central pathways mediating satiation — it works through gut nerve signals and direct brain effects to reduce food intake. Studies indicate that GLP-1 levels and meal responses may be altered in obese individuals, potentially contributing to overeating.
Clinical trials showed that two GLP-1 receptor agonists, exenatide and liraglutide (both approved for type 2 diabetes), produce weight loss in overweight subjects without diabetes. This established GLP-1 RAs as potential pharmacological treatments for obesity, a direction that has since been validated with the approval of higher-dose liraglutide (Saxenda) and semaglutide (Wegovy) specifically for weight management.
Holst, J J ·
RPEP-02197 · 2013Two distinct disruptions of the GHRH-GH-IGF1 axis occur in HIV/AIDS:
1. HIV lipodystrophy (associated with HAART): Suppressed GH production due to increased somatostatin tone, decreased ghrelin, elevated free fatty acids, and insulin resistance. Results in chronic inflammation, lipid abnormalities, and excess abdominal fat.
2. AIDS wasting syndrome: Elevated GH but low IGF-1 levels, indicating GH resistance — the body produces growth hormone but cannot respond to it properly.
Tesamorelin, a GHRH analog, is the only FDA-approved treatment for HIV-associated lipodystrophy, working by restoring GH pulsatility to reduce visceral adipose tissue.
Jain, Shobhit; Desai, Ninad; Bhangoo, Amrit ·
RPEP-02200 · 2013All BPC-157 treatment regimens counteracted the decrease in leak point pressure (LPP) in both transabdominal urethrolysis (TU) and vaginal dilatation (VD) rat models of stress urinary incontinence. At the 10 µg/kg intraperitoneal and oral doses, BPC-157-treated TU-rats and VD-rats achieved LPP values equivalent to healthy controls.
Immunohistochemical analysis revealed higher desmin (skeletal muscle marker), smooth muscle actin, and CD34 (angiogenesis marker) positivity in the urethral walls of BPC-157-treated rats compared to controls. Muscle-to-connective tissue ratios were also preserved. Notably, BPC-157 did not alter LPP in healthy rats, suggesting its effects are specific to injured tissue.
Jandric, Ivan; Vrcic, Hrvoje; Jandric Balen, Marica; Kolenc, Danijela; Brcic, Luka; Radic, Bozo; Drmic, Domagoj; Seiwerth, Sven; Sikiric, Predrag ·
RPEP-02207 · 2013Lacritin and lipocalin-1 are two tear proteins selectively deficient in dry eye disease. Lacritin is a prosecretory mitogen — meaning it both stimulates tear secretion and promotes cell growth — and has been shown to promote basal tearing when applied topically as a recombinant protein.
Active monomeric lacritin levels are suppressed by tear tissue transglutaminase, an enzyme whose expression is elevated in dry eye patients with ocular surface inflammation. Lipocalin-1 serves as the primary lipid-absorbing molecule of the tear film, preventing residual lipids from disrupting the eye surface wetting layer. It also functions as a carrier for vitamins and steroid hormones and as an endonuclease that clears potentially proinflammatory DNA from tears.
Karnati, Roy; Laurie, Diane E; Laurie, Gordon W ·
RPEP-02210 · 2013When administered locally into inflamed paws, the maximal analgesic effect was highest for 14-O-MeM6SU (50.6%), followed by β-endorphin (40.69%), fentanyl (37.44%), met-enkephalin (36.00%), and morphine (18.23%). The novel compound was more potent than all comparators.
Natural opioid peptides (met-enkephalin and β-endorphin) displayed a peripheral analgesic ceiling effect — they could not produce analgesia beyond a certain level — and their effects were confined to inflamed tissue. In contrast, at higher doses, 14-O-MeM6SU, morphine, and fentanyl also produced effects in non-inflamed tissue. All analgesic effects were reversed by the opioid antagonist naloxone-methiodide, confirming opioid receptor mediation.
Khalefa, Baled I; Mousa, Shaaban A; Shaqura, Mohammed; Lackó, Erzsébet; Hosztafi, Sándor; Riba, Pál; Schäfer, Michael; Ferdinandy, Péter; Fürst, Susanna; Al-Khrasani, Mahmoud ·
RPEP-02212 · 2013The review identifies multiple neuropeptide systems involved in mood regulation: corticotropin-releasing factor (CRF) and its related urocortins drive the stress response and are overactive in depression; neuropeptide Y appears to be protective against anxiety and stress; oxytocin has anxiolytic properties; substance P (via NK1 receptors) promotes anxiety and emotional distress; neuropeptide S promotes wakefulness and reduces anxiety; and PACAP modulates stress responses.
The central argument is that because current monoamine-targeting drugs fail a significant proportion of patients, these neuropeptide systems represent promising alternative or complementary therapeutic targets.
Kormos, Viktória; Gaszner, Balázs ·
RPEP-02215 · 2013Researchers successfully produced recombinant thymosin β4 (Tβ4) in bacteria (E. coli) and demonstrated that this lab-made version promoted angiogenesis (new blood vessel formation) just as effectively as the expensive chemically synthesized version. The recombinant Tβ4 activated endothelial cell proteolytic systems, inhibited cell adhesion, promoted cell migration, and stimulated capillary tube formation in Matrigel.
This was the first evidence that bacterially produced recombinant Tβ4 retains its angiogenesis-promoting activity in an in vitro endothelial cell model — proving it can replace costly synthetic peptide for research and potentially clinical applications.
Kozaczuk, Anna; Selmi, Anna; Bednarek, Radoslaw · In Vitro
RPEP-02217 · 2013Binge-like ethanol exposure during adolescence significantly reduced basal α-MSH (a melanocortin neuropeptide) levels in three key brain regions — the central nucleus of the amygdala (CeA), arcuate nucleus (Arc), and paraventricular nucleus (PVN) — in adult rats 25 days after the last ethanol exposure. Acute ethanol also increased AgRP (the melanocortin inverse agonist) in the Arc, and adolescent-exposed rats required higher ethanol doses to elicit this AgRP response. These lasting neuropeptide disturbances may contribute to excessive adult alcohol consumption.
Lerma-Cabrera, Jose Manuel; Carvajal, Francisca; Alcaraz-Iborra, Manuel; de la Fuente, Leticia; Navarro, Montserrat; Thiele, Todd E; Cubero, Inmaculada ·
RPEP-02218 · 2013Substance P (SP), a pain-signaling neuropeptide, was detected in the gingival crevicular fluid of teeth undergoing orthodontic movement with the Invisalign technique, but was not found in control teeth from the same patients that were not being moved. This is one of the first studies to demonstrate substance P release specifically during clear aligner orthodontic treatment.
Levrini, Luca; Sacerdote, Paola; Moretti, Sarah; Panzi, Silvia; Caprioglio, Alberto ·
RPEP-02219 · 2013Mice lacking the ghrelin gene had fewer progenitor cells in the hippocampus, reduced numbers of immature and newly generated neurons, and impaired memory performance on Y-maze and novel object recognition tests. Administering ghrelin to these knockout mice restored progenitor cell numbers to wild-type levels, increased new neuron formation, and reversed the memory deficits.
This demonstrates that endogenous ghrelin — not just externally administered ghrelin — plays a direct role in adult hippocampal neurogenesis, and that ghrelin's absence measurably impairs learning and memory.
Li, Endan; Chung, Hyunju; Kim, Yumi; Kim, Dong Hyun; Ryu, Jong Hoon; Sato, Takahiro; Kojima, Masayasu; Park, Seungjoon · Animal
RPEP-02222 · 2013Met-RANTES-treated mice showed significantly less behavioral hypersensitivity (pain) after partial sciatic nerve ligation. At the molecular level, treatment significantly reduced macrophage infiltration at the injury site, decreased secretion of pro-inflammatory cytokines (TNFα, IL-1β, IL-6, and IFNγ), and increased anti-inflammatory IL-10 levels.
Expression of opioid peptides — enkephalin, β-endorphin, and dynorphin mRNA — in damaged nerves was also significantly decreased in treated mice, suggesting that reducing inflammation reduced the compensatory opioid peptide response. The results demonstrate that CCL5 regulates the inflammatory microenvironment controlling pain sensitivity at the peripheral nerve injury site.
Liou, Jiin-Tarng; Mao, Chih-Chieh; Ching-Wah Sum, Daniel; Liu, Fu-Chao; Lai, Ying-Shu; Li, Jui-Chin; Day, Yuan-Ji ·
RPEP-02229 · 2013All nine patients tolerated the peptide-coupled cell infusion without serious adverse events. Patients receiving higher doses (more than 1 billion peptide-coupled cells) showed a measurable decrease in T cell reactivity against the myelin peptides used in the therapy.
This is significant because it suggests the treatment achieved its intended mechanism — reducing the specific immune response against myelin without broadly suppressing immunity. The therapy was feasible to manufacture from each patient's own blood cells and the seven myelin peptides covered multiple autoimmune targets simultaneously.
Lutterotti, Andreas; Yousef, Sara; Sputtek, Andreas; Stürner, Klarissa H; Stellmann, Jan-Patrick; Breiden, Petra; Reinhardt, Stefanie; Schulze, Christian; Bester, Maxim; Heesen, Christoph; Schippling, Sven; Miller, Stephen D; Sospedra, Mireia; Martin, Roland · Phase 1 Clinical Trial
RPEP-02231 · 2013Oral administration of the egg-derived tripeptide IRW (Ile-Arg-Trp) to spontaneously hypertensive rats (SHRs) reduced mean blood pressure by approximately 10 mmHg at 3 mg/kg and 40 mmHg at 15 mg/kg over 18 days of daily dosing.
The blood pressure reduction was accompanied by restoration of normal circadian blood pressure patterns, preservation of nitric oxide-dependent vasorelaxation, decreased plasma angiotensin II levels, reduced inflammatory markers, and less tissue fibrosis — all without changes in heart rate.
Majumder, Kaustav; Chakrabarti, Subhadeep; Morton, Jude S; Panahi, Sareh; Kaufman, Susan; Davidge, Sandra T; Wu, Jianping ·
RPEP-02241 · 2013This article describes the peptidomimetic design process that led to JMV 2959, a potent ghrelin receptor (GHS-R1a) antagonist built on a 1,2,4-triazole scaffold. Starting from the 28-amino-acid ghrelin peptide, the researchers progressively simplified the structure through medicinal chemistry to create a small-molecule antagonist. JMV 2959 has been extensively studied across multiple biological contexts, showing effects on food intake and obesity, addictive behaviors (including alcohol, nicotine, and drug reward), hyperactivity, and retinopathy.
Moulin, Aline; Brunel, Luc; Boeglin, Damien; Demange, Luc; Ryan, Johanne; M'Kadmi, Céline; Denoyelle, Séverine; Martinez, Jean; Fehrentz, Jean-Alain · Review
RPEP-02246 · 2013LL-37 was effective at killing extracellular S. aureus at nanomolar concentrations, while lactoferricin B required micromolar concentrations and the conventional antibiotics doxycycline and cefazolin required millimolar concentrations — a potency difference of roughly three orders of magnitude.
Critically, LL-37 was superior to conventional antibiotics at eliminating intracellular S. aureus within osteoblasts. Kinetic studies showed LL-37 acted rapidly against both extra- and intracellular bacteria. An unexpected finding was that LL-37 killed a clinical S. aureus strain more effectively than a standard laboratory (ATCC) strain, suggesting strong real-world applicability.
Noore, Jabeen; Noore, Adly; Li, Bingyun ·
RPEP-02249 · 2013The stapled BimBH3 peptide (BimSAHB), designed to have enhanced α-helical stability and improved binding to pro-survival Bcl-2 proteins, actually showed reduced binding affinity for its targets. The researchers attributed this to disruption of a network of stabilizing intramolecular interactions that exist in the bound state of the native (unstapled) peptide.
Furthermore, cells exposed to BimSAHB did not readily undergo apoptosis, strongly indicating that the stapled peptide is not inherently cell permeable — contradicting a key assumption behind its design as a therapeutic agent.
Okamoto, Toru; Zobel, Kerry; Fedorova, Anna; Quan, Clifford; Yang, Hong; Fairbrother, Wayne J; Huang, David C S; Smith, Brian J; Deshayes, Kurt; Czabotar, Peter E ·
RPEP-02255 · 2013NT-proBNP has established itself as a gold standard biomarker for heart failure with the following key characteristics:
- A cutoff of 300 pg/mL provides 99% sensitivity, 60% specificity, and 98% negative predictive value for ruling out acute heart failure
- NT-proBNP has a longer half-life and higher plasma concentration than BNP, making it easier to measure
- It strongly predicts death in both acute and chronic heart failure
- It predicts short- and long-term mortality in patients with suspected or confirmed unstable cardiovascular disease
- Levels are influenced by sex (higher in women), obesity (lower in obese individuals), and age (higher in elderly)
- It may also help estimate the onset timing of atrial fibrillation of unknown duration
Panagopoulou, Vasiliki; Deftereos, Spyridon; Kossyvakis, Charalampos; Raisakis, Konstantinos; Giannopoulos, Georgios; Bouras, Georgios; Pyrgakis, Vlasios; Cleman, Michael W ·
RPEP-02262 · 2013Synthetic monolayer membrane vesicles called "bolavesicles" successfully delivered two analgesic peptides — kyotorphin and leu-enkephalin — across the blood-brain barrier in mice, producing efficient and prolonged pain relief. The best results came from mixed bolavesicle formulations (GLH-19/GLH-20) with chitosan. A key innovation was the controlled release mechanism: the vesicles contain acetylcholine-like head groups that are broken down by cholinesterase enzymes specifically abundant in the brain, triggering peptide release at the target site. Pretreatment with pyridostigmine (a cholinesterase inhibitor that doesn't cross the BBB) enhanced the analgesic effect, confirming that brain-specific enzyme activity drives the release.
Popov, Mary; Abu Hammad, Ibrahim; Bachar, Tzach; Grinberg, Sarina; Linder, Charles; Stepensky, David; Heldman, Eliahu · Animal Study
RPEP-02269 · 2013Fast eating did not stimulate GLP-1 release in either age group, while slow eating increased circulating GLP-1 only in obese adolescents. PYY increased after both fast and slow eating in both groups, but slow eating was significantly more effective at stimulating PYY release in obese adolescents compared to adults.
Slow eating evoked higher satiety only in obese adolescents, with reduced hunger at 210 minutes. Obese adults showed no significant differences in satiety or hunger between eating rates. Postprandial insulin and triglyceride responses were higher in obese adults than adolescents regardless of eating speed, reflecting greater metabolic dysregulation with age and prolonged obesity.
Rigamonti, A E; Agosti, F; Compri, E; Giunta, M; Marazzi, N; Muller, E E; Cella, S G; Sartorio, A ·
RPEP-02274 · 2013The review consolidates evidence from multiple lines of research pointing to NPY as a stress resilience factor:
• Animal studies demonstrate that NPY promotes coping behaviors during stress, particularly in forebrain limbic and brainstem areas that regulate emotional responses.
• Genetic, physiological, and clinical data in humans implicate NPY as a potential resilience-to-stress factor.
• Reduced central nervous system NPY concentrations or function appear to be associated with PTSD.
• Specific PTSD symptoms (avoidance, hyperarousal, fear conditioning, impaired extinction) map onto known functions of the NPY system in the brain.
Collectively, the evidence suggests NPY deficiency may contribute to PTSD vulnerability rather than being merely a consequence of the disorder.
Sah, R; Geracioti, T D ·
RPEP-02279 · 2013In MDA-MB-231 triple-negative breast cancer xenografts in nude mice:
- GHRH antagonist JMR-132 alone: 46% tumor growth inhibition
- Docetaxel alone: 50% tumor growth inhibition
- Combination: 71.6% tumor growth inhibition (p<0.001)
In vitro, both JMR-132 and docetaxel reduced cell viability dose-dependently, with the combination producing significantly greater inhibition than either agent alone. PCR array analysis of tumor tissue revealed that JMR-132 interacts with signal transduction pathways involved in proliferation, apoptosis, and angiogenesis, explaining its multi-faceted anti-tumor mechanism.
Seitz, S; Rick, F G; Schally, A V; Treszl, A; Hohla, F; Szalontay, L; Zarandi, M; Ortmann, O; Engel, J B; Buchholz, S ·
RPEP-02282 · 2013Researchers engineered Bifidobacterium longum bacteria to produce human thymosin alpha-1 (Tα1), then fed these bacteria to mice orally every other day for two weeks. Compared to control bacteria, the Tα1-producing bacteria significantly increased CD3+CD4+ and CD3+CD8+ T cells in the blood, spleen, and thymus, and boosted CD4+CD8+ cells in the thymus and spleen.
The immune-stimulating cytokines IFN-γ and IL-12 were significantly elevated in serum, while TNF-α and IL-4 were unchanged — indicating selective activation of the Th1 (cellular immunity) pathway. After three months of treatment, the mice showed thymic hyperplasia (enlarged thymus) and lymph node enlargement, confirming sustained immune organ growth from oral delivery.
Shao, Congwen; Tian, Guojun; Huang, Yuanjian; Liang, Wenying; Zheng, Hang; Wei, Jiannan; Wei, Cheng; Yang, Cuilan; Wang, Hong; Zeng, Weisen · Animal
RPEP-02284 · 2013Both substance P (SP) and CGRP concentration-dependently stimulated keratinocyte proliferation and production of IL-1β, IL-6, TNF-α, and nerve growth factor (NGF). SP activated all three MAPK families (ERK1/2, JNK, p38) plus NFκB, while CGRP activated only ERK1/2 and p38.
The study revealed several novel findings: CGRP stimulates keratinocyte expression of both CGRP itself and its receptor complex (creating an autocrine amplification loop); SP and CGRP both stimulate IL-6 and TNF-α secretion (previously unknown); SP activates all three MAPK families plus NFκB in keratinocytes; and the inflammatory mediator production driven by both neuropeptides depends specifically on ERK1/2 and JNK activation, as inhibitors of these pathways reversed the effects.
Shi, Xiaoyou; Wang, Liping; Clark, J David; Kingery, Wade S ·
RPEP-02292 · 2013Six of eight participants showed improved scores on the communication and social interaction domains of the Autism Diagnostic Observation Schedule (ADOS-G). Caregivers of five participants reported positive effects, particularly in the quality of reciprocal communication.
However, standardized behavioral measures (Child Behavior Checklist T-scores and Aberrant Behavior Checklist scores) did not reach statistical significance, though some subcategories showed mild improvement trends. Critically, all eight participants showed excellent compliance and zero side effects across the entire treatment period, with normal blood pressure, blood, and urine results throughout.
Tachibana, Masaya; Kagitani-Shimono, Kuriko; Mohri, Ikuko; Yamamoto, Tomoka; Sanefuji, Wakako; Nakamura, Ayumi; Oishi, Masako; Kimura, Tadashi; Onaka, Tatsushi; Ozono, Keiichi; Taniike, Masako ·
RPEP-02293 · 2013The study revealed a highly specific pattern for peripheral substance P signaling in orofacial pain:
- Substance P (1 µg/50 µL) injected into the upper lip induced heat hyperalgesia but not cold hyperalgesia, mechanical hyperalgesia, or spontaneous pain behavior
- The NK1 receptor antagonist SR140333B (3 mg/kg, which does not cross the blood-brain barrier) reduced substance P-induced heat hyperalgesia, carrageenan-induced heat hyperalgesia, and both phases of the formalin response by ~50%
- SR140333B abolished heat hyperalgesia caused by infraorbital nerve constriction (trigeminal neuropathic pain model) but did not affect cold or mechanical hyperalgesia
- SR140333B did not reduce carrageenan-induced cold hyperalgesia
Because the NK1 antagonist cannot cross the BBB and substance P was injected peripherally, these results specifically demonstrate peripheral (not central) substance P/NK1 signaling in facial heat pain.
Teodoro, Fernanda C; Tronco Júnior, Marcos F; Zampronio, Aleksander R; Martini, Alessandra C; Rae, Giles A; Chichorro, Juliana G ·