RPEP-03402 · 2017LfcinB (4-9), with the sequence RRWQWR, entered E. coli cytoplasm without inducing membrane leakage. This was demonstrated by two independent methods: (1) SYTOX green exclusion showed no membrane damage, and (2) fluorescently labeled peptide entered cells without leakage of the cytoplasmic marker calcein.
The same behavior was observed in artificial membrane vesicles (GUVs) — the labeled peptide translocated across the lipid bilayer without leakage of the encapsulated probe AF647. Interaction with DNA significantly increased the peptide's fluorescence intensity, suggesting intracellular DNA binding as a potential antimicrobial mechanism.
Moniruzzaman, Md; Islam, Md Zahidul; Sharmin, Sabrina; Dohra, Hideo; Yamazaki, Masahito ·
RPEP-03406 · 2017Cathelicidin-PP is a 32-residue peptide (ASENGKCNLLCLVKKKLRAVGNVIKTVVGKIA) that adopts a β-sheet structure in membrane-mimetic environments. It demonstrated potent antimicrobial activity against bacteria and fungi, with particular effectiveness against Gram-negative bacteria. Scanning electron microscopy confirmed it kills bacteria by disrupting membrane integrity.
Beyond direct antimicrobial action, cathelicidin-PP significantly inhibited LPS-stimulated production of nitric oxide, TNF-α, IL-1β, and IL-6 in macrophages. This anti-inflammatory effect involved both MAPK (ERK, JNK, and p38) and NF-κB signaling pathways. The peptide also partially neutralized LPS in a dose-dependent manner. In live tree frogs, bacterial infection caused increased cathelicidin-PP expression in immune-related tissues, confirming its role in natural host defense.
Mu, Lixian; Zhou, Lei; Yang, Juanjuan; Zhuang, Li; Tang, Jing; Liu, Tong; Wu, Jing; Yang, Hailong · In Vitro Study
RPEP-03409 · 2017GHSR (growth hormone secretagogue receptor type 1a) constitutively — without agonist binding — inhibits the forward trafficking of multiple CaV channel subtypes, reducing their surface expression. This effect depends on the presence of CaVβ subunits, which normally help CaVα1 subunits leave the endoplasmic reticulum for the cell surface. GHSR's constitutive activity traps calcium channels intracellularly, suggesting a tonic suppressive effect on calcium signaling in brain regions expressing both GHSR and these calcium channels.
Mustafá, Emilio R; López Soto, Eduardo J; Martínez Damonte, Valentina; Rodríguez, Silvia S; Lipscombe, Diane; Raingo, Jesica ·
RPEP-03410 · 2017For the first time, researchers demonstrated the presence and localization of Substance P (SP) and its receptor NK-1R in both human and rat adipose-derived stem cells (ADSCs). Using immunofluorescence, they showed that SP and NK1R are present in both the cytoplasm and nucleus of ADSCs, with NK1R levels being higher in the nucleus. Western blot analysis revealed different NK1R isoforms with distinct subcellular locations. Critically, SP was shown to induce proliferation and mitogenesis in ADSCs through the NK1R pathway.
Muñoz, Miguel; Muñoz, Mario F; Ayala, Antonio ·
RPEP-03415 · 2017More than 1,100 unique peptides derived from milk protein hydrolysis were identified within the mammary gland — produced before the milk was ever expressed. These peptides originated from 42 different milk proteins. Among them, 306 peptides were predicted to have bioactive properties.
Plasmin was predicted to be the primary protease responsible for the in-gland protein hydrolysis. The study's careful methodology — collecting milk directly into antiprotease cocktails on ice with immediate freezing — ensured these peptides were genuinely produced within the mammary gland rather than during sample handling.
Nielsen, Søren D; Beverly, Robert L; Dallas, David C ·
RPEP-03417 · 2017Antimicrobial peptides (AMPs) in the skin are a double-edged sword. On one hand, they protect against infections by killing bacteria, viruses, fungi, and parasites. They also promote wound healing, stimulate cell growth and migration, and strengthen the skin barrier. On the other hand, these same peptides actively contribute to the development and progression of several skin diseases.
The review identifies specific roles in multiple conditions: AMPs drive inflammatory processes in psoriasis, contribute to the altered immune response in atopic dermatitis (eczema), play a role in the redness and inflammation of rosacea, and are involved in acne, lupus, and systemic sclerosis. The key AMPs discussed include defensins, cathelicidins (like LL-37), S100 proteins, ribonucleases, and dermcidin.
Niyonsaba, François; Kiatsurayanon, Chanisa; Chieosilapatham, Panjit; Ogawa, Hideoki · Review
RPEP-03420 · 2017Resolvin D1 (RvD1) and chemerin (a ChemR23 ligand) both reduced inflammatory pain in early and late phases of CFA-induced hindpaw inflammation in rats. However, this pain relief was completely prevented by peripheral blockade of the μ-opioid receptor using low-dose local naloxone, or by local injection of antibodies against β-endorphin and met-enkephalin.
Importantly, RvD1 did not directly activate opioid receptors — it did not stimulate G-protein-coupled MOR signaling or β-arrestin recruitment. It also did not stimulate the release of β-endorphin from macrophages or neutrophils. The interaction appears to involve TRPA1 channels: naloxone blocked the antinociceptive effects of the TRPA1 inhibitor HC-030031 both in vivo and in vitro (calcium influx in dorsal root ganglion neurons). Peripheral naloxone alone lowered mechanical pain thresholds, indicating that endogenous opioid tone is necessary for the normal balance of pain signaling.
Oehler, Beatrice; Mohammadi, Milad; Perpina Viciano, Cristina; Hackel, Dagmar; Hoffmann, Carsten; Brack, Alexander; Rittner, Heike L ·
RPEP-03424 · 2017Cosmeceutical peptides fall into four functional categories — signal peptides that stimulate extracellular matrix production (especially collagen), structural peptides that stabilize skin architecture, carrier peptides that deliver trace elements like copper to cells, and neurotransmitter-inhibiting peptides that reduce muscle contraction to minimize wrinkles.
The review notes that while peptides offer advantages including selectivity, low immunogenicity, and involvement in multiple skin functions, their clinical evidence for efficacy is often weak. Absorption through skin remains a challenge due to low lipophilicity and high molecular weight, though penetration enhancers, chemical modification, and encapsulation can improve delivery.
Pai, Varadraj Vasant; Bhandari, Prasana; Shukla, Pankaj · Review
RPEP-03426 · 2017The review identifies common epigenetic mechanisms — histone deacetylation and DNA methylation — that regulate neuropeptide expression in both alcoholism and stress disorders. BDNF, CRF, NPY, and opioid peptides (nociceptin, dynorphin) are key molecules whose expression is altered by epigenetic modifications in specific brain regions. Histone deacetylases and methyltransferases have been identified as shared molecular mechanisms driving the interaction between stress and alcohol dependence, making them promising therapeutic targets.
Palmisano, Martina; Pandey, Subhash C ·
RPEP-03432 · 2017KPV peptide cannot cross the skin by passive diffusion — levels were undetectable. But combining two enhancement technologies dramatically changed this: microneedles alone increased permeation to 4.4 μg/cm²/h, iontophoresis (electrical current) alone was 8-fold better than microneedles, and combining both technologies boosted delivery 35-fold over microneedles alone.
Skin retention also improved dramatically — 10-fold higher KPV was retained in the skin when using iontophoresis or the combination approach. Confocal imaging confirmed the peptide penetrated beyond 100 μm depth, reaching the lower epidermis.
Pawar, Kasturi; Kolli, Chandra S; Rangari, Vijaya K; Babu, R Jayachandra · In Vitro Laboratory Study
RPEP-03435 · 2017In dogs with spontaneous ileal inflammation (n=8) compared to healthy controls (n=7), the percentage of Substance P-producing neurons was similar in both the myenteric plexus (15–16%) and submucosal plexus (24–26%). However, key differences emerged in receptor distribution: muscle cells and immune cells in inflamed tissue overexpressed NK1R immunoreactivity, while nitrergic (nNOS-positive) neurons expressing NK1R showed a trend toward decrease in inflamed dogs (41% vs 65%, P=0.11).
SP-immunoreactive mucosal nerve fibers also trended toward decreased density in inflamed tissue (P=0.07). These findings suggest that inflammation shifts NK1R from neuronal to non-neuronal tissue compartments, potentially altering how Substance P signaling affects gut function.
Polidoro, Giulia; Giancola, Fiorella; Fracassi, Federico; Pietra, Marco; Bettini, Giuliano; Asti, Martina; Chiocchetti, Roberto ·
RPEP-03442 · 2017Low-dose intranasal oxytocin (8 IU) delivered via a novel Breath Powered device significantly increased emotional salience of faces in adults with autism (P=0.02, d=0.63, η²=0.18), while the higher dose (24 IU) did not reach statistical significance (P=0.12, d=0.4). Remarkably, the 8 IU effects occurred without significantly increasing blood plasma oxytocin levels, suggesting direct nose-to-brain delivery. No significant effects were found on other social-cognitive tasks (reading the mind in the eyes, emotional dot probe, face morphing).
Quintana, D S; Westlye, L T; Hope, S; Nærland, T; Elvsåshagen, T; Dørum, E; Rustan, Ø; Valstad, M; Rezvaya, L; Lishaugen, H; Stensønes, E; Yaqub, S; Smerud, K T; Mahmoud, R A; Djupesland, P G; Andreassen, O A ·
RPEP-03443 · 2017ACE-inhibitory peptides produced during milk fermentation are resistant to gastrointestinal digestion and can inhibit ACE in the renin-angiotensin system in their intact form. Their production and potency depend on multiple factors: the type of starter culture (lactic acid bacteria species, yeast), the milk protein substrate (casein type, whey protein), the specific peptide composition, and pre- and post-fermentation processing.
The antihypertensive effects of fermented milk products have been confirmed through in vitro studies, animal models, and human clinical trials. Several ACE-inhibitory peptides from fermented milk are now available in commercial products marketed for blood pressure support.
Rai, Amit Kumar; Sanjukta, Samurailatpam; Jeyaram, Kumaraswamy ·
RPEP-03444 · 2017The Lip-DOPE-MPL-GP2 formulation generated the highest IFN-γ+ CD8+ T cell and cytotoxic T lymphocyte responses among all tested formulations, as measured by ELISpot and flow cytometry. In both prophylactic (vaccination before tumor challenge) and therapeutic (vaccination after tumor establishment) experiments, mice immunized with this formulation had smaller tumors and longer survival compared to other groups. The combination of DOPE (fusogenic lipid) and MPL (adjuvant) was key to both the immune response and anti-tumor efficacy.
Razazan, Atefeh; Behravan, Javad; Arab, Atefeh; Barati, Nastaran; Arabi, Leila; Gholizadeh, Zahra; Hatamipour, Mahdi; Reza Nikpoor, Amin; Momtazi-Borojeni, Amir Abbas; Mosaffa, Fatemeh; Ghahremani, Mohamad Hosein; Jaafari, Mahmoud Reza ·
RPEP-03446 · 2017Contrary to expectations, the appetite-suppressing gut peptides GLP-1 and PYY do not appear to be major drivers of weight loss after sleeve gastrectomy. In 10 obese patients studied before and 3 months after surgery, GLP-1 release after meals was not stimulated regardless of eating speed or surgical status. PYY levels did increase after surgery (higher post-op than pre-op), but the speed of eating made no difference.
Interestingly, fast eating produced greater satiety than slow eating in both pre- and post-operative states, contradicting common dietary advice. Hunger and satiety responses to food were similar before and after surgery. Sleeve gastrectomy did improve insulin resistance regardless of eating speed. The authors conclude that anorexigenic gut peptide responses play a "negligible" role in sleeve gastrectomy-induced weight loss, suggesting other mechanisms (mechanical restriction, altered ghrelin, neural signaling) are more important.
Rigamonti, Antonello Emilio; Bini, Silvia; Rocco, Maria Cristina; Giardini, Vittorio; Massimini, Diego; Crippa, Maria Grazia; Saluzzi, Antonella; Casati, Marco; Marazzi, Nicoletta; Perotti, Mario; Cimino, Vincenzo; Grassi, Guido; Sartorio, Alessandro; Pincelli, Angela Ida · Clinical Study
RPEP-03451 · 2017Using Rosetta Design and Amber molecular modeling software, researchers designed and screened exendin-4 analogs with mutations at trypsin cleavage sites. The top candidate, TSME-1, retained biological activity comparable to native exendin-4 while being almost completely resistant to trypsin digestion. When administered orally to C57BL/6J mice, TSME-1 significantly normalized blood glucose levels in glucose tolerance tests and showed significantly higher oral bioavailability than both native exendin-4 and the intermediate exendin4-cysteine analog.
Sai, Wenbo; Tian, Hong; Yang, Kangmin; Tang, Daoqi; Bao, Jinxiao; Ge, Yang; Song, Xiaoda; Zhang, Yu; Luo, Cheng; Gao, Xiangdong; Yao, Wenbing ·
RPEP-03455 · 2017In 250 consecutive STEMI patients, increased plasma apelin concentrations at admission independently predicted 6-month all-cause mortality after adjusting for age, diabetes, systolic blood pressure, heart rate, glomerular filtration rate, Killip class, left ventricular ejection fraction, BNP, and sensitive troponin I.
Combining apelin with BNP and troponin I further improved predictive accuracy compared to any single biomarker. Notably, apelin levels were associated with markers of ischemic heart failure severity (reflecting the heart's functional decline) but not with markers of ischemic insult severity (reflecting the acute damage) — suggesting apelin reflects the heart failure response rather than the ischemic injury itself.
Sans-Roselló, Jordi; Casals, Gregori; Rossello, Xavier; González de la Presa, Bernardino; Vila, Montserrat; Duran-Cambra, Albert; Morales-Ruiz, Manuel; Ferrero-Gregori, Andreu; Jiménez, Wladimiro; Sionis, Alessandro ·
RPEP-03458 · 2017No collagen hydrolysate modulated collagen biosynthesis in human knee cartilage explants — the primary benefit these supplements claim to provide.
The products showed disparate effects: Peptan F 2000 (fish) enhanced the activities of cartilage-degrading aggrecanases ADAMTS4 and ADAMTS5 in vitro, without proteoglycan loss from tissue. Mobiforte (porcine) showed the opposite aggrecanase effect. Mobiforte and Peptan F 5000 elevated IL-6, MMP-1, MMP-3, and MMP-13 in cartilage explants — all markers of inflammation and cartilage destruction — while Peptan F 2000 did not.
Biophysical analysis (MALDI-TOF-MS, NMR, AFM) revealed marked differences in total peptide number and shared peptides between the fish and porcine products.
Schadow, Saskia; Simons, Viktor S; Lochnit, Guenter; Kordelle, Jens; Gazova, Zuzana; Siebert, Hans-Christian; Steinmeyer, Juergen ·
RPEP-03461 · 2017Starting with 41 peptides predicted by in silico algorithms as the highest-affinity binders to HLA-A*0201, the study found a dramatic funnel of attrition:
- 41 peptides predicted as strong binders
- 19 actually showed strong binding to HLA-A2
- 10 formed stable HLA-A2-peptide complexes and induced CD8+ T cells in transgenic mice
- Only 5 induced T cell responses in PBMCs from ESO-vaccinated melanoma patients
The 5 immunogenic peptides shared features not predicted by algorithms: strong binding, high complex stability, and multiple large hydrophobic and aromatic amino acids. This reveals that current prediction tools capture only part of what makes a peptide immunogenic in humans.
Schmidt, Julien; Guillaume, Philippe; Dojcinovic, Danijel; Karbach, Julia; Coukos, George; Luescher, Immanuel ·
RPEP-03465 · 2017Two fusion peptide surrogates with equal hydrophobicity but different sequences were compared:
- wtFP-tag (wild-type LFLGFLG): preserved α-helical conformation with a Gly-rich ridge in DPC micelles (membrane mimic); assembled into trimers in membranes (detected by Western blot)
- scrFP-tag (scrambled FGLLGFL): maintained helical structure in low-polarity HFIP solvent but largely lost helical structure in DPC micelles; failed to form membrane oligomers
Both peptides were tagged with an independently folding epitope sequence for detection without interfering with FP structure. The results demonstrate that the conserved FLGFLG tandem repeat is essential for maintaining the specific helical conformation and trimerization ability required for HIV membrane fusion.
Serrano, Soraya; Huarte, Nerea; Rujas, Edurne; Andreu, David; Nieva, José L; Jiménez, María Angeles ·
RPEP-03467 · 2017Two siRNA-NES peptide conjugates were synthesized: one linked to a TFIIIA-derived NES peptide and another to an HIV-1 REV-derived NES peptide. The HIV-1 REV conjugate suppressed BCR/ABL expression to 4.0% (96% silencing) at 200 nM and 6.3% at 50 nM. The TFIIIA conjugate suppressed to 8.3% at 200 nM and 11.6% at 50 nM. By comparison, native siRNA only suppressed to 36.3% at 200 nM and 30.2% at 50 nM. Complexing the conjugates with amphiphilic peptideβ7 enabled non-toxic cellular uptake with excellent silencing efficiency.
Shinkai, Yasuhiro; Kashihara, Shinichi; Minematsu, Go; Fujii, Hirofumi; Naemura, Madoka; Kotake, Yojiro; Morita, Yasutaka; Ohnuki, Koichiro; Fokina, Alesya A; Stetsenko, Dmitry A; Filichev, Vyacheslav V; Fujii, Masayuki ·
RPEP-03470 · 2017The chimeric peptide LFchimera (combining lactoferricin 17-30 and lactoferampin 265-284) demonstrated the most prominent bactericidal activity, membrane permeabilization, and membrane depolarization against both Gram-positive and Gram-negative bacteria serving as biological warfare agent simulants.
Arginine residues were identified as crucial for antimicrobial activity: lysine-to-arginine substitutions increased activity (particularly affecting LFampin265-284), while arginine-to-lysine substitutions decreased activity (particularly in LFcin17-30). This establishes arginine content as a key design parameter for optimizing lactoferrin-derived antimicrobial peptides.
Sijbrandij, Tjitske; Ligtenberg, Antoon J; Nazmi, Kamran; Veerman, Enno C I; Bolscher, Jan G M; Bikker, Floris J ·
RPEP-03471 · 2017This comprehensive review from the primary BPC-157 research group presents BPC 157 (Body Protection Compound, a 15-amino-acid peptide derived from human gastric juice) as an integrative mediator of the body's stress response. The authors argue that BPC 157 counteracts a remarkably wide range of stress-induced damage across multiple organ systems: gastrointestinal tract, skin, tendons, ligaments, muscle, bone, nerve, cornea, and brain.
Key proposed mechanisms include: promotion of angiogenesis (new blood vessel formation), interaction with the dopamine, serotonin, and GABA neurotransmitter systems, modulation of the nitric oxide (NO) system, and regulation of gene expression (Fos, c-Jun, Egr-1). The authors report that BPC 157 has shown no side effects in clinical trials and that a lethal dose (LD1) has not been reached in toxicity studies. They frame the peptide as stable in human gastric juice, making oral administration viable.
Sikiric, Predrag; Seiwerth, Sven; Rucman, Rudolf; Drmic, Domagoj; Stupnisek, Mirjana; Kokot, Antonio; Sever, Marko; Zoricic, Ivan; Zoricic, Zoran; Batelja, Lovorka; Ziger, Tihomil; Luetic, Kresimir; Vlainic, Josipa; Rasic, Zarko; Bencic, Martina Lovric · Review
RPEP-03474 · 2017In rats with chemically induced Parkinson's-like symptoms, the peptide Selank (an analog of taftsin) reduced anxiety levels in the elevated plus maze test. Neither Selank nor Semax (an ACTH 4-10 fragment analog) affected motor activity or passive defensive behavior in the parkinsonian rats.
Notably, Selank's anti-anxiety effect persisted even after toxic damage to the substantia nigra — the brain region destroyed in Parkinson's disease. This suggests Selank's anxiolytic mechanism operates independently of the dopaminergic neurons lost in parkinsonism, consistent with its previously demonstrated effects in healthy rodents under stress.
Slominsky, P A; Shadrina, M I; Kolomin, T A; Stavrovskaya, A V; Filatova, E V; Andreeva, L A; Illarioshkin, S N; Myasoedov, N F · Animal Study
RPEP-03494 · 2017After Roux-en-Y gastric bypass (RYGB), GLP-1 levels were significantly elevated, and brain responses to food cues were reduced in key reward and taste-processing regions. Using the GLP-1 receptor blocker exendin 9-39, the researchers demonstrated that blocking GLP-1 signaling reversed these brain changes — restoring the heightened food-cue responses that existed before surgery. This provides direct evidence that GLP-1 mediates the reduced food motivation seen after bariatric surgery.
Specifically, after RYGB, brain activation decreased in the rolandic operculum and caudate nucleus when viewing food pictures (P=0.03) and in the insula when tasting palatable food (P=0.003). Blocking GLP-1 receptors with exendin 9-39 reversed the reduced activation in the caudate nucleus (P=0.02) and insula (P=0.002).
Ten Kulve, Jennifer S; Veltman, Dick J; Gerdes, Victor E A; van Bloemendaal, Liselotte; Barkhof, Frederik; Deacon, Carolyn F; Holst, Jens J; Drent, Madeleine L; Diamant, Michaela; IJzerman, Richard G · Interventional
RPEP-03495 · 2017Ivermectin inhibited KLK5 and CAMP (cathelicidin) gene expression and protein secretion in normal human epidermal keratinocytes (NHEK) stimulated with calcitriol. These results were confirmed in two 3D skin models — reconstructed human epidermis (RHE) and human skin ex vivo.
The anti-inflammatory effects extended beyond the cathelicidin pathway: ivermectin also reduced secretion of inflammatory cytokines IL-8, IL-6, and the chemokine MCP-1 (CCL2). This demonstrates that ivermectin targets the upstream molecular drivers of rosacea inflammation rather than just masking symptoms.
Thibaut de Ménonville, Séverine; Rosignoli, Carine; Soares, Estelle; Roquet, Manon; Bertino, Béatrice; Chappuis, Jean-Paul; Defoin-Platel/Chaussade, Claire; Piwnica, David ·
RPEP-03498 · 2017In streptozotocin-induced diabetic rats, treatment with the GHRH agonist MR-409 (15 μg/kg) prevented retinal morphological damage and particularly preserved retinal ganglion cell survival. MR-409 upregulated NRF-2-dependent antioxidant gene expression, downregulated pro-inflammatory cytokines and adhesion molecules, reduced VEGF expression while increasing PEDF expression, and decreased vascular permeability. GHRH and GHRH-R expression were significantly downregulated in both diabetic rat retinas and human diabetic retinas (postmortem). Treatment with the GHRH antagonist MIA-602 worsened retinal morphology, confirming that GHRH signaling is neuroprotective.
Thounaojam, Menaka C; Powell, Folami L; Patel, Sagar; Gutsaeva, Diana R; Tawfik, Amany; Smith, Sylvia B; Nussbaum, Julian; Block, Norman L; Martin, Pamela M; Schally, Andrew V; Bartoli, Manuela ·
RPEP-03502 · 2017Meta-analysis of 17 studies with 516 total participants/subjects found:
- Overall central-peripheral oxytocin correlation: r=0.29 (95% CI: 0.14-0.42, p=0.003)
- Under basal (resting) conditions: r=0.08 (p=0.31) — NO significant correlation
- After intranasal oxytocin administration: r=0.66 (p<0.0001) — STRONG correlation
- After experimentally induced stress: r=0.49 (p=0.001) — MODERATE correlation
These results indicate that central and peripheral oxytocin release are coordinated after stress or exogenous administration, but not under resting conditions. The common research practice of using blood oxytocin to approximate brain oxytocin at baseline is not supported.
Valstad, Mathias; Alvares, Gail A; Egknud, Maiken; Matziorinis, Anna Maria; Andreassen, Ole A; Westlye, Lars T; Quintana, Daniel S ·
RPEP-03505 · 2017Marine fish-derived proteins and peptides — particularly those obtained from enzymatic hydrolysis of fish processing by-products — show a broad range of activities relevant to skincare: antioxidant, antimicrobial, anti-aging, anti-photoaging, and matrix metalloproteinase (MMP) inhibition. Fish-derived collagen specifically demonstrates abilities in skin repair and tissue regeneration.
The review highlights that these peptides are increasingly being developed into cosmeceutical products, taking advantage of both their bioactivity and the sustainability angle of using fish processing waste as the raw material.
Venkatesan, Jayachandran; Anil, Sukumaran; Kim, Se-Kwon; Shim, Min Suk · Narrative Review
RPEP-03507 · 2017Compared to normal disc tissue, TDR periprosthetic tissue showed dramatically elevated TNFα (5.17 vs 0.05, p=0.02), VEGF (3.02 vs 0.02, p=0.02), and substance P (4.15 vs 0.08, p=0.02). Even compared to painful degenerative disc disease tissue, TDR tissue had higher IL-1β (p=0.01), VEGF (p=0.04), and substance P (p=0.01).
Five factors (TNFα, IL-1β, VEGF, NGF, substance P) strongly correlated with wear particle number, macrophage count, and blood vessel density. Key correlations: TNFα with wear particles (p<0.001, ρ=0.63), VEGF with macrophages (p=0.001, ρ=0.71), and NGF with blood vessels (p<0.001, ρ=0.70). PDGFbb, NGF, and substance P expression localized predominantly to blood vessels and nerve fibers.
Veruva, Sai Y; Lanman, Todd H; Isaza, Jorge E; Freeman, Theresa A; Kurtz, Steven M; Steinbeck, Marla J ·
RPEP-03508 · 2017An oral ghrelin receptor agonist called HM01 significantly reduced cancer-related wasting (cachexia) in mice with colon tumors. Treated mice had increased food intake, body weight, fat mass, muscle mass, and bone mineral density, while energy expenditure decreased. Notably, these benefits occurred even though HM01 did not reduce the inflammatory cytokines (IL-6 and MIC-1) or muscle degradation markers (MuRF-1 and MAFbx) that drive cachexia. This suggests HM01 works by boosting caloric intake and reducing energy burning rather than blocking the inflammatory wasting pathways directly.
The study also mapped the timeline of cachexia progression: the inflammatory cytokine MIC-1 rose first, followed by IL-6, and muscle degradation markers increased last.
Villars, Fabienne O; Pietra, Claudio; Giuliano, Claudio; Lutz, Thomas A; Riediger, Thomas · Animal Study
RPEP-03509 · 2017All five tested NSAIDs — diclofenac, ibuprofen, paracetamol, aspirin, and celecoxib — caused rapid and persistent drops in both lower esophageal sphincter and pyloric sphincter pressure in rats. BPC-157, given at doses of 10 μg/kg or 10 ng/kg, minimized the initial pressure drop and restored sphincter pressures to normal values in all NSAID groups.
The peptide was effective regardless of administration route (intraperitoneal injection, intragastric administration, or dissolved in drinking water) and worked against both traditional NSAIDs and the COX-2 selective inhibitor celecoxib. This consistent counteraction across multiple NSAIDs and routes suggests a robust protective mechanism.
Vitaic, S; Stupnisek, M; Drmic, D; Bauk, L; Kokot, A; Klicek, R; Vcev, A; Luetic, K; Seiwerth, S; Sikiric, P ·
RPEP-03510 · 2017Patients heterozygous for the rs696217 SNP (GT genotype) in the preproghrelin gene achieved 38.1% BMI reduction at 52 weeks post-surgery, compared to 30.5% for GG homozygotes (p<0.001). Carrying the rs1126535 C allele in the CD40L gene was associated with lower BMI reduction at 52 weeks (28.1% vs 33.2%, p=0.049). Variants in the ghrelin receptor (rs490683), another preproghrelin SNP (rs27647), and adiponectin gene (rs2241766) showed no significant association with weight loss outcomes.
Vitolo, Edoardo; Santini, Eleonora; Seghieri, Marta; Giannini, Livia; Coppedè, Fabio; Rossi, Chiara; Dardano, Angela; Solini, Anna ·
RPEP-03512 · 2017Substance P drives liver fibrosis during cholestatic liver injury by acting through the neurokinin-1 receptor (NK-1R). Knocking out NK-1R in mice or blocking it with the antagonist L-733,060 significantly reduced liver fibrosis, as shown by decreased sirius red staining, lower fibrosis gene expression, and reduced TGF-β1 levels in serum.
The mechanism involves a dual effect on cellular senescence: Substance P decreases senescence in hepatic stellate cells (keeping them active and fibrosis-promoting) while increasing senescence in cholangiocytes (bile duct cells). Blocking NK-1R reversed both of these effects. Human tissue from primary sclerosing cholangitis patients also showed elevated expression of Substance P and NK-1R compared to healthy controls.
Wan, Ying; Meng, Fanyin; Wu, Nan; Zhou, Tianhao; Venter, Julie; Francis, Heather; Kennedy, Lindsey; Glaser, Trenton; Bernuzzi, Francesca; Invernizzi, Pietro; Glaser, Shannon; Huang, Qiaobing; Alpini, Gianfranco · Animal Study
RPEP-03517 · 2017Researchers developed a systematic method to create cyclic peptides that can be taken orally — solving one of the biggest challenges in peptide drug development. Their approach combined two strategies: (1) N-methylation of the peptide backbone to improve intestinal permeability, and (2) protecting charged groups with lipophilic prodrug modifications to allow absorption.
They applied this to create an orally bioavailable RGD-containing hexapeptide that selectively binds the integrin αvβ3 — a receptor involved in tumor blood vessel growth. The final compound showed biological effects in mice after oral administration, proving the concept works in a living organism. The method involved screening combinatorial libraries for permeability, then systematically optimizing for receptor selectivity and oral absorption.
Weinmüller, Michael; Rechenmacher, Florian; Kiran Marelli, Udaya; Reichart, Florian; Kapp, Tobias G; Räder, Andreas F B; Di Leva, Francesco Saverio; Marinelli, Luciana; Novellino, Ettore; Muñoz-Félix, José M; Hodivala-Dilke, Kairbaan; Schumacher, Adi; Fanous, Joseph; Gilon, Chaim; Hoffman, Amnon; Kessler, Horst · Basic Science (Peptide Chemistry + Animal Proof Of Concept)
RPEP-03522 · 2017A growth hormone-releasing hormone (GHRH) antagonist inhibited the invasion and migration of endometrial cancer cells in a dose-dependent manner. The mechanism involved suppression of Twist and N-cadherin — two proteins critical for cancer cell motility and the epithelial-to-mesenchymal transition. When the GHRH receptor was knocked down using siRNA, the antagonist's suppressive effects were abolished, confirming the action is mediated specifically through the GHRH receptor. Similarly, independently silencing Twist or N-cadherin each suppressed cell motility, validating these as key downstream targets.
Wu, Hsien-Ming; Huang, Hong-Yuan; Schally, Andrew V; Chao, Angel; Chou, Hung-Hsueh; Leung, Peter C K; Wang, Hsin-Shih ·
RPEP-03523 · 2017The dendritic theranostic agent P-FU 4, which combines Substance P targeting with four 5-FU drug molecules and a near-infrared imaging dye, demonstrated several key outcomes: 16% drug loading capacity, dose-dependent cytotoxicity against cancer cells with minimal effect on normal cells, preferential uptake by tumor cells through NK1R-mediated interaction, and 60.2% tumor inhibition rate in a mouse model.
The nanoparticle self-assembled from the dendritic construct, and the dendron architecture prevented the fluorescent dye from aggregation-mediated quenching, maintaining strong near-infrared signal for real-time monitoring of drug distribution.
Wu, Junchen; Zhou, Yuren; Li, Shang; Qu, Dahui; Zhu, Wei-Hong; Tian, He ·
RPEP-03524 · 2017Salmon muscle proteins digested with Pseudoalteromonas sp. SQN1 crude enzymes produced the strongest antioxidant hydrolysate: 74.06% DPPH radical scavenging and 69.71% hydroxyl radical scavenging. Collagen was easier to degrade but produced weaker antioxidants.
The purified fraction U2-S2-I showed strong antioxidant activity:
- DPPH scavenging IC50: 0.263 mg/mL
- Hydroxyl radical scavenging IC50: 0.512 mg/mL
- Oxygen radical absorption capacity: 1.960 mmol Trolox equivalent/g
- Protected plasmid DNA from hydroxyl radical damage at levels comparable to the original hydrolysate, indicating it contained the primary bioactive peptides.
Wu, Ribang; Chen, Leilei; Liu, Dan; Huang, Jiafeng; Zhang, Jiang; Xiao, Xiao; Lei, Ming; Chen, Yuelin; He, Hailun ·
RPEP-03526 · 2017DP7 demonstrated potent antimicrobial activity on its own against all tested clinical isolates, with minimum inhibitory concentrations at or below 32 mg/L. When combined with vancomycin or azithromycin, the effects were frequently synergistic rather than merely additive. Notably, the synergy between DP7 and azithromycin was strongest against the most resistant strains — those carrying two or more azithromycin-resistance genes (ermA, ermB, ermC, mefA, msrA). Electron microscopy showed no major structural damage to bacteria, suggesting the synergistic mechanism operates at the molecular level rather than through physical membrane destruction.
Wu, Xiaozhe; Li, Zhan; Li, Xiaolu; Tian, Yaomei; Fan, Yingzi; Yu, Chaoheng; Zhou, Bailing; Liu, Yi; Xiang, Rong; Yang, Li ·
RPEP-03528 · 2017Trypsin induced a concentration-dependent biphasic response (contraction at 100 nM, relaxation at 1 μM) exclusively in esophageal circular smooth muscle, not longitudinal muscle. The response was mediated through a PAR2 → TRPV1 → substance P signaling pathway in sensory neurons, with substance P acting via neurokinin receptors NK1 and NK2.
Gap junctions between smooth muscle cells were essential for the response — gap junction uncouplers (carbenoxolone and octanol) abolished the trypsin-induced contractions entirely. The PAR2-activating peptide SLIGKV-NH2 produced only contraction (monophasic), suggesting the relaxation component involves additional mechanisms at higher trypsin concentrations.
Xiaopeng, Bai; Tanaka, Yoshimasa; Ihara, Eikichi; Hirano, Katsuya; Nakano, Kayoko; Hirano, Mayumi; Oda, Yoshinao; Nakamura, Kazuhiko ·
RPEP-03532 · 2017The review establishes that hyperglycemia alone plays a limited role in cardiovascular disease progression in T2DM — metabolic risk factors like insulin resistance, hypertension, obesity, and dyslipidemia are the major drivers. GLP-1 receptor agonists and SGLT-2 inhibitors demonstrated cardiovascular benefits in their safety trials, attributed to diverse extra-pancreatic effects beyond glucose control.
These benefits include reductions in blood pressure, body weight, and lipid abnormalities. The review proposes studying combinations of GLP-1 RAs, SGLT-2 inhibitors, and pioglitazone in high-risk diabetic patients and even in non-diabetic patients with insulin resistance for potential cardiovascular protection.
Yandrapalli, Srikanth; Aronow, Wilbert S ·
RPEP-03539 · 2017This systematic review of 40 neuroimaging studies mapped how gut peptide hormones control appetite by activating specific brain regions. The hunger hormone ghrelin activates the prefrontal cortex (decision-making), amygdala (emotional eating), and insula (body awareness) while suppressing the hypothalamus. Satiety signals — GLP-1, PYY, CCK, leptin, glucose, and insulin — do the opposite, affecting the same brain regions in reverse.
This creates a clear picture: gut peptides don't just signal 'hungry' or 'full' — they reshape activity across an entire neural circuit that governs food decisions, emotional responses to food, and metabolic regulation.
Zanchi, Davide; Depoorter, Antoinette; Egloff, Laura; Haller, Sven; Mählmann, Laura; Lang, Undine E; Drewe, Jürgen; Beglinger, Christoph; Schmidt, André; Borgwardt, Stefan · Systematic Review
RPEP-03542 · 2017Young athletes with functional knee pain who took 5 grams of bioactive collagen peptides daily for 12 weeks experienced significantly greater reduction in activity-related knee pain compared to placebo. The collagen group improved by 19.5 points on the VAS pain scale versus 13.9 points for placebo (p=0.046). Independent physician assessments confirmed the result (16.7 vs 12.2 points, p=0.021). Participants taking collagen peptides also significantly reduced their use of additional treatments like taping, physical therapy, or anti-inflammatory drugs.
Zdzieblik, Denise; Oesser, Steffen; Gollhofer, Albert; König, Daniel · Rct
RPEP-03546 · 2017Chronic subcutaneous administration of the mitochondria-targeted peptide SS-31 at 1 mg/kg/day and 3 mg/kg/day for 12 weeks reduced atherosclerotic plaque area and size in ApoE knockout mice fed a Western diet. SS-31 suppressed oxidative stress (reduced DHE staining, lower 8-OHDG, increased SOD activity), reduced systemic inflammation (decreased ICAM-1, MCP-1, and IL-6 levels), and inhibited cholesterol influx by downregulating CD36 and LOX-1 expression, preventing foam cell formation. Plaque composition also changed, suggesting more stable plaques.
Zhang, Meng; Zhao, Hongting; Cai, Jing; Li, Huihui; Wu, Qi; Qiao, Tong; Li, Kuanyu ·
RPEP-03552 · 2017SS-31 treatment administered immediately after spinal cord injury and for the following two days produced multiple protective effects in the lungs:
- Attenuated lung edema and tissue damage
- Reduced apoptosis (cell death) in alveolar type II cells, which are critical for lung function
- Decreased total macrophages, pro-inflammatory M1 macrophages, and neutrophil infiltration
- Lowered reactive oxygen species (ROS) levels
- Reversed mitochondrial dysfunction
- Inhibited NLRP3 inflammasome activation, a key driver of inflammatory lung damage
These results demonstrate that targeting mitochondrial dysfunction with SS-31 can control the inflammatory cascade that leads to secondary lung injury after spinal cord trauma.
Zhu, Liu-Long; Li, Mao-Qiang; He, Fan; Zhou, Shao-Bo; Jiang, Wu ·
RPEP-03554 · 2017Dogs receiving capromorelin at 3 mg/kg daily showed a mean food consumption increase of 60.55% (±39.87%) compared to a decrease of 11.15% (±14.23%) in placebo dogs (P < 0.001). Body weight increased by a mean of 5.96% (±1.76%) in the treated group versus 0.053% (±1.14%) in controls (P < 0.001).
The drug was well-tolerated across all 12 treated dogs, with no abnormalities on physical examination, serum chemistry, or hematology. The only observed clinical sign was increased salivation in some treated dogs. This demonstrated that activating the ghrelin receptor can dramatically and safely stimulate appetite in dogs.
Zollers, Bill; Rhodes, Linda; Heinen, Ernst ·
RPEP-03555 · 2017Over 40 cyclic peptide drugs are currently in clinical use, with approximately one new cyclic peptide drug entering the market annually. While the vast majority of approved cyclic peptides derive from natural products (antimicrobials, human peptide hormones), new techniques based on rational design and in vitro evolution now enable de novo development of cyclic peptide ligands for previously untargetable proteins. Several de novo-designed cyclic peptides are already under clinical evaluation.
Zorzi, Alessandro; Deyle, Kaycie; Heinis, Christian ·
RPEP-03564 · 2018Peptides isolated from seaweed proteins have demonstrated ACE-inhibiting (blood pressure-lowering), antioxidant, and antidiabetic activities in laboratory studies. Multiple seaweed species have yielded bioactive peptides through enzymatic hydrolysis that could serve as functional food ingredients or drug candidates for cardiovascular disease and diabetes prevention. However, most evidence comes from in vitro studies, and large-scale production, in vivo validation, and safety testing are still needed.
Admassu, Habtamu; Gasmalla, Mohammed Abdalbasit A; Yang, Ruijin; Zhao, Wei ·
RPEP-03565 · 2018LEAP-2 (liver-expressed antimicrobial peptide 2) is a recently discovered endogenous antagonist of the ghrelin receptor (GHSR1a). It works as a noncompetitive allosteric blocker — meaning it doesn't compete with ghrelin directly but instead changes the receptor's shape to prevent ghrelin from activating it. In lab experiments, LEAP-2 blocked ghrelin's ability to trigger calcium signaling, and in animal studies, it impaired ghrelin's metabolic effects.
The review presents LEAP-2 as ghrelin's natural counterbalance in energy metabolism: where ghrelin drives hunger and promotes fat storage, LEAP-2 opposes these effects. This makes LEAP-2 a promising therapeutic target for obesity and metabolic diseases involving ghrelin system dysregulation.
Al-Massadi, Omar; Müller, Timo; Tschöp, Matthias; Diéguez, Carlos; Nogueiras, Ruben · Narrative Review
RPEP-03571 · 2018Neutrophil extracellular traps (NETs) from type 2 diabetes patients contained LL-37 but lacked antibacterial activity compared to healthy controls. Key findings:
- NETs from both treatment-naive hyperglycemic and well-controlled diabetic patients failed to kill E. coli effectively
- Clarithromycin significantly increased LL-37 externalization on NETs from well-controlled diabetic patients
- This restored NET antibacterial capacity against E. coli
- Clarithromycin-enhanced NETs promoted wound healing by activating and differentiating primary skin fibroblasts
- The effect required well-controlled blood sugar (normoglycemic T2D patients), not treatment-naive hyperglycemic patients
Arampatzioglou, Athanasios; Papazoglou, Dimitrios; Konstantinidis, Theocharis; Chrysanthopoulou, Akrivi; Mitsios, Alexandros; Angelidou, Iliana; Maroulakou, Ioanna; Ritis, Konstantinos; Skendros, Panagiotis ·