RPEP-04121 · 2019In rats with SU5416/hypoxia-induced pulmonary hypertension, six weeks of sacubitril/valsartan treatment significantly reduced right ventricular systolic pressure (62±4 vs 46±5 mmHg), right ventricular hypertrophy (RV/LV+S ratio: 0.74±0.06 vs 0.46±0.06), and myocardial collagen content (8.2±0.3 vs 6.4±0.4 µg/50 µg protein) compared to placebo.
Right ventricular contractility also improved (31.2±1.8 vs 43.1±3.6 mm/s). Valsartan alone did not achieve these improvements. The combination treatment increased lung levels of ANP, BNP, and cGMP while decreasing plasma endothelin-1, and reduced pulmonary vascular wall thickness — indicating benefits to both the heart and the lung vasculature.
Clements, Richard T; Vang, Alexander; Fernandez-Nicolas, Ana; Kue, Nouaying R; Mancini, Thomas J; Morrison, Alan R; Mallem, Krishna; McCullough, Danielle J; Choudhary, Gaurav ·
RPEP-04122 · 2019Transgenic chickens overexpressing ovotransferrin or avian β-defensin-3 (AvβD3) showed antimicrobial peptide expression in egg white, breast muscle, and serum at both RNA and protein levels.
The antimicrobial effects were substantial: transgene expression significantly reduced growth of aerobic bacteria and coliforms in breast muscle, and decreased Salmonella enterica growth in egg white. The peptides inhibited growth of both human and chicken bacterial pathogens as well as spoilage bacteria in vitro.
Beyond the direct antimicrobial effects, the transgenic birds also showed changes to their immune systems, including increased proportions of CD8+ T cells in blood — suggesting the overexpressed peptides also boosted innate immunity.
Cooper, Caitlin A; Tizard, Mark L; Stanborough, Tamsyn; Moore, Sean C; Chandry, P Scott; Jenkins, Kristie A; Wise, Terry G; O'Neil, Terri E; Layton, Daniel S; Morris, Kirsten R; Moore, Robert J; Fegan, Narelle; Doran, Timothy J ·
RPEP-04124 · 2019The ghrelin receptor (GHSR) in the brain drives binge-like high-fat eating in mice independently of ghrelin itself. Plasma levels of ghrelin and its natural blocker LEAP2 didn't change during binge eating, and injecting ghrelin systemically didn't alter binge behavior. However, blocking the receptor's constitutive (always-on) activity in the brain — using either LEAP2 or a synthetic blocker (K-(D-1-Nal)-FwLL-NH2) delivered directly to the brain — reduced binge-like high-fat intake. Notably, blocking only ghrelin-triggered receptor activity (using [D-Lys3]-GHRP-6 or JMV2959) did not reduce binge eating, confirming it's the receptor's baseline signaling, not ghrelin binding, that drives this behavior.
Cornejo, María Paula; Castrogiovanni, Daniel; Schiöth, Helgi B; Reynaldo, Mirta; Marie, Jacky; Fehrentz, Jean-Alain; Perello, Mario · Animal Study
RPEP-04126 · 2019Tripeptide linkers with all-L or single D-alanyl residues effectively released cytotoxic maytansinoid metabolites inside cells. D-alanyl residues didn't impair activity unless directly attached to the self-immolative group. Extending the maytansinoid side chain increased bystander killing without affecting direct cytotoxicity. The best-performing ADCs showed improved in vivo efficacy compared to previous maytansinoid conjugate designs.
Costoplus, Juliet A; Veale, Karen H; Qiu, Qifeng; Ponte, Jose F; Lanieri, Leanne; Setiady, Yulius; Dong, Ling; Skaletskaya, Anna; Bartle, Laura M; Salomon, Paulin; Wu, Rui; Maloney, Erin K; Kovtun, Yelena V; Ab, Olga; Lai, Kate; Chari, Ravi V J; Widdison, Wayne C ·
RPEP-04131 · 2019This Cochrane systematic review found that Cerebrolysin — a pig-brain-derived peptide preparation given by intravenous infusion — showed statistically significant improvements in cognition and global function in people with vascular dementia, but the evidence was rated 'very low quality' across the board.
Pooling data from three studies (420 participants), Cerebrolysin improved cognitive function scores (SMD 0.36, 95% CI 0.13–0.58). For global function, response rates were 2.69 times higher in the Cerebrolysin group (two studies, 379 participants, RR 2.69, 95% CI 1.82–3.98). No excess adverse effects were found (RR 0.91, 95% CI 0.29–2.85).
However, the reviewers concluded these data are 'not definitive.' All included studies had high risk of bias, there was significant heterogeneity between studies, and no new studies had been published since the previous 2013 Cochrane review. The effects may be too small to be clinically meaningful.
Cui, Shuhui; Chen, Ning; Yang, Mi; Guo, Jian; Zhou, Muke; Zhu, Cairong; He, Li · Systematic Review
RPEP-04133 · 2019In spontaneously hypertensive rats (SHRs), mild TBI induced significant long-term increases in both cytoplasmic and mitochondrial superoxide production in middle cerebral arteries at 2 weeks post-injury — an effect not seen in normotensive rats. Expression of the NADPH oxidase subunit Nox4 was also increased. Daily treatment with the mitochondria-targeted peptide SS-31 (5.7 mg/kg/day, i.p.) reversed all these oxidative stress markers to normal levels. NADPH oxidase inhibition (apocynin) also reduced the persistent oxidative stress, confirming the mechanistic pathway.
Czigler, Andras; Toth, Luca; Szarka, Nikolett; Berta, Gergely; Amrein, Kriszitina; Czeiter, Endre; Lendvai-Emmert, Dominika; Bodo, Kornelia; Tarantini, Stefano; Koller, Akos; Ungvari, Zoltan; Buki, Andras; Toth, Peter ·
RPEP-04134 · 2019The review identified that the NS2B-NS3 protease active site is shallow and open-pocketed, making it a challenging but critical drug target. Early inhibitors used two basic amino acid residues followed by an electrophilic warhead (such as trifluoromethyl ketones, aldehydes, or boronic acids) that covalently binds to the catalytic serine residue (Ser135). More advanced strategies include incorporating transition metals to create metallopeptide inhibitors and cyclizing linear peptides into macrocyclic structures to improve binding and stability.
The authors found that different functional group modifications significantly influence both activity and selectivity across the three flavivirus proteases, providing structure-activity relationships that can guide future drug design efforts.
da Silva-Júnior, Edeildo Ferreira; de Araújo-Júnior, João Xavier ·
RPEP-04137 · 2019No statistically significant difference was found between cod protein hydrolysate (CPH) and casein control for postprandial acylated ghrelin concentrations (mean difference: 1.05 pg/mL, 95% CI 0.97–1.13, P = 0.266). The total area under the curve for ghrelin was virtually identical: CPH 17,518 pg/mL × min versus control 17,272 pg/mL × min (P = 0.991).
Subjective appetite measures were also unchanged: no differences between CPH and control for satiety (P = 0.794) or fullness (P = 0.996). The results were consistently null across all time points (0, 20, 40, 80, and 180 minutes postprandially).
Dale, Hanna Fjeldheim; Jensen, Caroline; Hausken, Trygve; Lied, Einar; Hatlebakk, Jan Gunnar; Brønstad, Ingeborg; Hoff, Dag Arne Lihaug; Lied, Gülen Arslan ·
RPEP-04152 · 2019The chimeric tri-functional peptide combined three functional domains into one molecule:
1. A cell-penetrating peptide (CPP) for cellular uptake
2. A nuclear localization sequence (NLS) for targeting to the nucleus
3. An interfering peptide that blocks the TEAD-YAP protein-protein interaction
Results demonstrated:
• Successful cell penetration and nuclear localization confirmed by flow cytometry and fluorescence microscopy
• Apoptotic (cell death) effects in tumor cell lines
• Anti-tumoral effects in vivo in breast cancer xenograft mouse models
• The specific nuclear delivery of the interfering cargo was essential for the anti-cancer effect
Dominguez-Berrocal, Leticia; Cirri, Erica; Zhang, Xiguang; Andrini, Laura; Marin, Gustavo H; Lebel-Binay, Sophie; Rebollo, Angelita ·
RPEP-04153 · 2019At baseline, African Americans had significantly lower peptide YY (PYY; p<0.05), lower ghrelin (p=0.02), and higher leptin (p<0.05) compared to Whites. Despite these hormonal differences, no racial differences were observed in actual food intake at laboratory-controlled meals.
In the exercise intervention, leptin increased in African Americans in the 8 KKW exercise group compared to Whites (p=0.01), but no other race-by-group interactions were evident for appetite hormones, appetite ratings, or food intake. The disconnect between hormonal differences and behavioral outcomes suggests that appetite regulation in the context of obesity is more complex than hormone levels alone.
Dorling, James L; Church, Timothy S; Myers, Candice A; Höchsmann, Christoph; White, Ursula A; Hsia, Daniel S; Martin, Corby K; Apolzan, John W ·
RPEP-04163 · 2019Cereals like wheat, rice, corn, barley, oats, and millet contain proteins that, when broken down (hydrolyzed), release peptides with significant antioxidant activity. These food-derived peptides fight oxidative stress through multiple mechanisms: donating hydrogen atoms or electrons to neutralize free radicals, chelating (binding) metals that catalyze oxidation, and regulating enzymes involved in oxidation-reduction processes.
While the health benefits of whole grains were previously attributed mainly to fiber (glucans) and polyphenols, this review highlights that bioactive peptides from grain proteins represent an underappreciated category of health-promoting compounds in everyday foods.
Esfandi, Ramak; Walters, Mallory E; Tsopmo, Apollinaire · Review
RPEP-04177 · 2019Using untargeted plasma peptidomics, researchers identified 14 peptide substances with concentrations that varied according to kidney function. Seven were most likely to be elevated in CKD patients. The peptidomic score model achieved an area under the curve of 0.87 (95% CI: 0.815-0.919; p < 0.0001), indicating strong diagnostic accuracy.
The score was significantly higher in CKD than non-CKD patients (2.539 ± 0.264 vs -0.938 ± 0.169). Remarkably, the model also predicted CKD stages with a Spearman correlation of 0.83 and concordance index of 0.899 (95% CI: 0.863-0.927). In univariate analysis, the peptidomic score was most strongly associated with C-reactive protein, sodium, and uric acid — substances not previously prioritized in CKD peptide research.
Gajjala, Prathibha R; Bruck, Heike; Noels, Heidi; Heinze, Georg; Ceccarelli, Francesco; Kribben, Andreas; Saez-Rodriguez, Julio; Marx, Nikolaus; Zidek, Walter; Jankowski, Joachim; Jankowski, Vera ·
RPEP-04184 · 2019Silencing the peptide transporter TAP in tumor cells forced them to present a new set of peptide antigens that the immune system could recognize and attack. Tumor-targeted delivery of TAP siRNA via a nucleolin aptamer inhibited tumor growth across multiple tumor models without measurable toxicity. The approach was comparably effective to vaccination against mutation-generated neoantigens, potentiated the effects of PD-1 antibody and Flt3 ligand, and induced TAP-independent peptide presentation in human tumor cells.
Garrido, Greta; Schrand, Brett; Rabasa, Ailem; Levay, Agata; D'Eramo, Francesca; Berezhnoy, Alexey; Modi, Shrey; Gefen, Tal; Marijt, Koen; Doorduijn, Elien; Dudeja, Vikas; van Hall, Thorbald; Gilboa, Eli ·
RPEP-04186 · 2019The review identifies substance P, calcitonin gene-related peptide (CGRP), vasoactive intestinal peptide (VIP), and neuropeptide Y as the four major neuropeptides involved in joint pain — both in generating pain signals after trauma and in modulating pain reduction. Critically, the neuropeptide changes observed in subchondral bone and synovial tissue are mirrored in the central nervous system, indicating a bidirectional communication system.
These neuropeptides interact with each other and with cytokines in a complex cascade that determines how pain signals are generated, transmitted, and perceived. The joint functions as an integrated organ where local neuropeptide signaling and CNS processing work together to respond to mechanical load, injury, and inflammation.
Gatenholm, Birgitta; Brittberg, Mats ·
RPEP-04189 · 2019Molecular dynamics (MD) simulations have made significant progress over the past two decades in accurately predicting how peptides fold, move, and take shape. Peptides have become a favored test system for computational methods because their smaller size makes them tractable for simulation while still being relevant to protein structure prediction and drug design.
However, the accuracy of these simulations depends entirely on the mathematical models (force fields) used to describe molecular interactions. A major remaining challenge is simulating intrinsically disordered peptides — those that don't fold into fixed shapes — where current force fields still struggle to accurately capture their flexible behavior.
Georgoulia, Panagiota S; Glykos, Nicholas M · Review
RPEP-04192 · 2019The GRPR-targeting antagonist peptide RM1, when labeled with lutetium-177, proved more stable than the agonist peptide AMBA in mouse, canine, and human sera. Degradation followed the order: mouse sera (fastest) > canine > human sera (slowest), meaning the peptide lasts longest in human blood.
Higher radioconcentrations caused faster degradation of 177Lu-labeled RM1 during storage at 2–8°C. Adding stabilizers significantly improved shelf stability, with gentisic acid outperforming ascorbic acid. These findings support RM1 antagonist as the more promising candidate for both PET imaging and potential therapy of prostate cancer.
Ghosh, Arijit; Woolum, Karen; Kothandaraman, Shankaran; Tweedle, Michael F; Kumar, Krishan · In Vitro Study
RPEP-04198 · 2019The review covers five advances in primary headache disorders:
1. CGRP receptor antagonists (gepants): Rimegepant and ubrogepant completed Phase 3 trials for acute migraine, offering effective non-vasoconstrictor alternatives to triptans
2. CGRP monoclonal antibodies for prevention: Three licensed (erenumab, fremanezumab, galcanezumab) with eptinezumab to follow — the first migraine-specific preventive treatments, effective and well tolerated
3. Neuromodulation: Transcranial magnetic stimulation, noninvasive vagus nerve stimulation (nVNS), and external trigeminal nerve stimulation licensed for migraine
4. Cluster headache advances: nVNS effective for acute and preventive treatment; galcanezumab effective for episodic cluster headache prevention in a controlled trial
5. Premonitory phase understanding: Recognizing prodromal symptoms may help explain apparent migraine triggers and improve self-management
Goadsby, Peter J ·
RPEP-04200 · 2019The authors propose that circulating gut-derived peptides — including somatostatin, cholecystokinin, glucagon-like peptide 1, and vasoactive intestinal peptide — form a coordinated parasympathetic endocrine system (PES) with the dorsal motor nucleus of the vagus (DMV) as its integrative controller.
Beyond their well-known satiety and digestive effects, these peptides broadly increase parasympathetic signaling and directly antagonize sympathetic signaling in mammals. The authors present anatomical evidence (vagal projections to gut secretory cells), physiological control mechanisms (peptide-mediated parasympathetic modulation), and examples of direct PES antagonism of sympathetic activity to support this conceptual framework.
Gorky, Jonathan; Schwaber, James ·
RPEP-04206 · 2019GLP-1 receptor agonists demonstrated neuroprotective effects across multiple animal models of neurological disease. In Parkinson's disease models, they protected dopaminergic neurons and preserved motor function. In Alzheimer's disease models, they improved nearly all neuropathological features and cognitive functions, including reducing amyloid beta peptide aggregation. In stroke models, they reduced cerebral infarct area and improved neurological deficits.
The mechanisms appear to involve inhibition of oxidative stress, inflammation, and apoptosis (programmed cell death), as well as improvement of synaptic plasticity — the brain's ability to form and strengthen connections. These benefits were observed even in animals without diabetes, suggesting the neuroprotective effects are independent of blood sugar control.
Grieco, Maddalena; Giorgi, Alessandra; Gentile, Maria Cristina; d'Erme, Maria; Morano, Susanna; Maras, Bruno; Filardi, Tiziana ·
RPEP-04213 · 2019All published studies investigating BPC-157 have demonstrated consistently positive and prompt healing effects for various musculoskeletal soft tissue injuries, including tendon, ligament, and skeletal muscle damage. Benefits were observed for both traumatic (direct injury) and systemic insults, including hyperkalemia and hypermagnesemia.
BPC-157 appears particularly promising for hypovascular and hypocellular tissues like tendons and ligaments that are notoriously difficult to heal. Few studies have reported adverse reactions to BPC-157 administration. However, the review identifies critical gaps: nearly all evidence comes from small rodent models, only a handful of research groups have conducted in-depth studies over the past two decades, and the precise healing mechanisms have not been fully elucidated. Human clinical data is absent.
Gwyer, Daniel; Wragg, Nicholas M; Wilson, Samantha L ·
RPEP-04215 · 2019A pair of leucine zipper-based compounds was synthesized: Lz(E)-CPP (negatively charged zipper + cell-penetrating peptide) and Nanog-Lz(K) (positively charged zipper + cargo protein). When mixed at equimolar concentrations and applied to cells, the Nanog-Lz(K)/Lz(E)-CPP hybrid was successfully delivered into cells. Nanog protein reached the nucleus and exerted its proper transcriptional function after nuclear transport — demonstrating that the delivery system preserved protein activity.
Hakata, Yoshiyuki; Michiue, Hiroyuki; Ohtsuki, Takashi; Miyazawa, Masaaki; Kitamatsu, Mizuki ·
RPEP-04216 · 2019After matched 10 kg weight loss, the two groups showed strikingly different appetite peptide responses:
• Fasting ghrelin decreased more after RYGB than diet (P=0.04)
• Post-meal ghrelin AUC increased after dieting but not surgery (P=0.01)
• Hunger AUC increased after diet but not RYGB (P<0.01)
• Prospective food consumption AUC increased after diet vs RYGB (P<0.01)
• Satiety AUC increased after RYGB but decreased after dieting (P<0.01)
• Free fatty acid AUC increased more after RYGB (P=0.02)
Notably, actual food intake at a test lunch decreased similarly in both groups, and fasting glucose and insulin improved equally — suggesting that the metabolic benefits of weight loss per se are independent of method, but appetite regulation is fundamentally different.
Halliday, Tanya M; Polsky, Sarit; Schoen, Jonathan A; Legget, Kristina T; Tregellas, Jason R; Williamson, Kayla M; Cornier, Marc-Andre ·
RPEP-04217 · 2019LLLT with 685 nm at 8 J/cm² effectively reduced mechanical hyperalgesia in the acid-induced chronic muscle pain (fibromyalgia) model. The analgesic effect was completely abolished by: (1) pretreatment with NK1 receptor antagonist RP-67580, (2) deletion of the Tac1 gene encoding Substance P (Tac1-/- mice), and (3) pretreatment with TRPV1 antagonist capsazepine. However, ASIC3 antagonist APETx2 did not block the effect.
This demonstrates that LLLT analgesia is mediated by intramuscular Substance P's antinociceptive (pain-reducing) signaling through NK1 receptors and involves TRPV1 activation — revealing an unexpected pain-relieving role for a neuropeptide traditionally associated with pain promotion.
Han, Der-Sheng; Lee, Cheng-Han; Shieh, Yih-Dar; Chen, Chih-Cheng ·
RPEP-04218 · 2019In HT22 mouse hippocampal cells treated with toxic prion peptide PrP (106-126):
- Tβ4 increased autophagy markers LC3A/B and Beclin1, protecting against prion-induced neurotoxicity
- Tβ4 maintained balance between autophagy markers and AKT/mTOR pathway factors competitively against prion effects
- Cholinergic signaling markers (ChTp and AChE) were preserved by Tβ4 against prion-induced disruption
- All protective effects were reversed by 3-MA (autophagy inhibitor), confirming autophagy as the mechanism
- Results demonstrate Tβ4 maintains cholinergic signaling through autophagy induction
Han, Hye-Ju; Kim, Sokho; Kwon, Jungkee ·
RPEP-04219 · 2019T cells from pmel-1 transgenic mice targeting the mutated (neoantigen) version of the gp100 peptide showed enhanced recognition as measured by IFN-γ production. When used in adoptive cell transfer, neoantigen-targeting T cells achieved complete and durable regression of large, established, vascularized B16 melanoma tumors.
Critically, neoantigen targeting required less lymphodepleting conditioning than targeting the wild-type peptide, suggesting reduced treatment toxicity. The study also uncovered that enforced expression of the IL-2 receptor alpha chain (CD25) on mutation-reactive CD8+ T cells further improved their anti-tumor function, revealing a new strategy for enhancing neoantigen-targeted immunotherapy.
Hanada, Ken-Ichi; Yu, Zhiya; Chappell, Gabrielle R; Park, Adam S; Restifo, Nicholas P ·
RPEP-04221 · 2019Using CRISPR to systematically knock out all 14 immune-inducible antimicrobial peptide (AMP) genes in Drosophila — including attacins, cecropins, diptericins, drosocin, drosomycin, metchnikowin, and defensin — researchers demonstrated that AMPs are essential for in vivo defense against Gram-negative bacteria and fungi.
Critically, the study revealed remarkable specificity: individual AMPs contributed the majority of killing activity against specific pathogens, rather than all AMPs working equally against all microbes. AMPs also worked synergistically — combinations were more effective than predicted from individual contributions. Flies lacking all 14 AMPs were highly susceptible to infections.
Hanson, Mark Austin; Dostálová, Anna; Ceroni, Camilla; Poidevin, Mickael; Kondo, Shu; Lemaitre, Bruno · Animal
RPEP-04223 · 2019CGRP (calcitonin gene-related peptide) has been definitively proven as a central driver of migraine through decades of converging evidence: anatomical colocalization with pain-producing meningeal blood vessels, elevated levels during migraine attacks, intravenous CGRP triggering migraines only in migraineurs, and clinical efficacy of drugs blocking CGRP.
Critically, PET imaging studies showed that CGRP receptor antagonists achieved no brain receptor occupancy at effective antimigraine doses — proving the therapeutic action is peripheral, not central. This revolutionized migraine understanding: migraine pain is at least partly peripheral in origin.
Two drug classes have emerged from this science: (1) monoclonal antibodies given by injection that neutralize CGRP peptide (fremanezumab, galcanezumab, eptinezumab) or block its receptor (erenumab) for migraine prevention; and (2) oral small-molecule CGRP receptor antagonists (gepants) for both acute treatment (ubrogepant, rimegepant) and prevention (atogepant). All have shown consistent efficacy in large, multicenter RCTs.
Hargreaves, Richard; Olesen, Jes · Review
RPEP-04230 · 2019The review establishes three primary mechanisms by which milk protein-derived peptides lower postprandial glucose. First, they delay gastric emptying, slowing the rate at which carbohydrates enter the small intestine. Second, they enhance incretin hormone responses — particularly GLP-1 and GIP — which are the same hormones mimicked by blockbuster diabetes drugs like semaglutide. Third, they directly increase postprandial insulin secretion.
These effects have been demonstrated in both healthy subjects and patients with type 2 diabetes. The bioactive peptides released during milk protein digestion are the proposed mediators, creating a physiological milieu that naturally amplifies the body's blood sugar control mechanisms.
Hidayat, Khemayanto; Du, Xuan; Shi, Bi-Min ·
RPEP-04236 · 2019Using computer simulations, researchers discovered that polyarginine (R8) cell-penetrating peptides enter cells by punching temporary water pores through the cell membrane. When these peptides were attached to small nanoparticle cargoes via linkers, their delivery efficiency actually improved — the nanoparticles extended the lifetime of the water pore, giving more peptide-cargo complexes time to pass through.
Critically, linker length was the key design variable. Maximum delivery efficiency occurred when the linker was about half the thickness of the cell membrane. Linkers that were too long caused two problems: they blocked the water pore with the nanoparticle cargo, reducing delivery, and they could leave the pore open too long, potentially killing the cell. This provides a clear design rule for engineering peptide-drug conjugates.
Hu, Juanmei; Lou, Yimin; Wu, Fengmin · Computational
RPEP-04237 · 2019Plasma kisspeptin levels rise significantly throughout pregnancy, primarily produced by the placenta. The review found that kisspeptin levels could serve as a biomarker for detecting miscarriage risk, pre-eclampsia, gestational trophoblastic neoplasia (GTN), and fetal development problems. Kisspeptin may also play a role in triggering labor by stimulating oxytocin secretion during term pregnancy.
Hu, Kai-Lun; Zhao, Hongcui; Yu, Yang; Li, Rong ·
RPEP-04255 · 2019This mini-review surveys all known Bax inhibitors — peptides, small molecules, and antibodies — that can prevent mitochondria-dependent programmed cell death (apoptosis). While drugs that activate Bax have been developed for cancer treatment (to kill tumor cells), no clinically effective therapeutics have been developed that suppress Bax-induced cell death to rescue essential cells in conditions like neurodegeneration, retinal degeneration, stroke, organ preservation, and lung fibrosis.
Bax-inhibiting peptides (BIPs) represent a key class of these inhibitors, delivered via cell-penetrating peptide technology to reach mitochondrial membranes where Bax exerts its cell-killing activity.
Jensen, Kelsey; WuWong, David Jasen; Wong, Sean; Matsuyama, Mieko; Matsuyama, Shigemi · Review
RPEP-04258 · 2019Serum thymosin beta-4 was significantly lower in NAFLD patients (3.20 ± 0.98 mg/L) compared to healthy controls (5.53 ± 1.24 mg/L), a 42% reduction (P<0.001).
Multivariate logistic regression identified Tβ4 as an independent predictor of NAFLD (OR=0.343, 95% CI 0.240-0.491, P<0.001), meaning higher Tβ4 levels were strongly protective. Other independent predictors were LDL cholesterol, ALT, and IL-6.
Tβ4 showed significant negative correlations with total cholesterol (r=-0.163), triglycerides (r=-0.253), AST (r=-0.143), GGT (r=-0.245), and IL-6 (r=-0.155). Tβ4 was positively correlated with adiponectin (r=0.143), an anti-inflammatory and insulin-sensitizing hormone.
Jiang, Yong; Zhang, Ying; Ma, Cui-Hua; Zhang, Zhi-Guang; Li, Man; Ji, Ying-Lan; Qi, Feng-Xiang ·
RPEP-04261 · 2019Beta-glucan from yeast (Saccharomyces cerevisiae) triggers sheep ruminal epithelial cells to produce the antimicrobial peptide sheep beta-defensin-1 (SBD-1) through a specific signaling pathway: TLR-2 → MyD88 → NF-κB/MAPK.
When researchers knocked down TLR-2 or MyD88, beta-glucan-induced SBD-1 production dropped significantly. Blocking either the MAPK or NF-κB pathways also reduced SBD-1 expression, but NF-κB inhibition had the larger effect, suggesting it's the dominant pathway controlling defensin production in response to yeast components.
This means the gut lining of sheep actively recognizes yeast cell wall components through innate immune receptors and responds by ramping up antimicrobial peptide production — explaining part of how probiotic yeasts boost gut defense.
Jin, Xin; Zhang, Man; Yang, Yin-Feng · Laboratory Study
RPEP-04263 · 2019Once-weekly semaglutide (0.5 mg and 1.0 mg) offered superior cost-per-outcome versus exenatide extended-release and dulaglutide for type 2 diabetes. Semaglutide was the most effective at getting patients to all three treatment targets: HbA1c below 7.0%, HbA1c below 7.0% without hypoglycemia or weight gain, and a combined target of ≥1.0% HbA1c reduction with ≥5.0% weight loss.
Critically, the cost-to-efficacy ratio also favored semaglutide — meaning it wasn't just more effective, but more cost-effective per patient who reached treatment goals. This held true for both the simple glycemic target and the more demanding composite endpoints.
Johansen, Pierre; Hunt, Barnaby; Iyer, Neeraj N; Dang-Tan, Tam; Pollock, Richard F · Health Economics / Cost Effectiveness Analysis
RPEP-04266 · 2019From 1,267 initially identified publications, 74 clinical studies met inclusion criteria. Cathelicidin (LL-37), alpha-defensins, and beta-defensins 1-3 were the most studied antimicrobial peptides in periodontal contexts. LL-37 showed significant correlations with clinical periodontal indices (probing depth, clinical attachment loss) and bacteriological indices. Results for human beta-defensins (hBDs) were inconsistent across studies due to heterogeneous methodologies, diagnostic criteria, and assay techniques. LL-37 and alpha-defensins were identified as the most promising candidates for periodontal biomarkers.
Jourdain, Marie-Laure; Velard, Frédéric; Pierrard, Loïc; Sergheraert, Johan; Gangloff, Sophie C; Braux, Julien ·
RPEP-04267 · 2019Researchers engineered smart nanoparticles decorated with three different targeting peptides — a cell-penetrating peptide, a tumor blood vessel-targeting peptide, and a mitochondria-targeting peptide — to deliver both the chemotherapy drug irinotecan and a microRNA (miR-200) that blocks cancer spread. The nanoparticles were coated with a pH-sensitive PEG layer that sheds in the acidic tumor environment, exposing the targeting peptides only where they're needed.
In lab tests on colon cancer cells, the dual-delivery system triggered cancer cell death through multiple pathways while showing low toxicity to healthy blood and intestinal cells. In mice with colorectal tumors, the nanoparticles inhibited tumor growth and reduced the systemic side effects that typically accompany irinotecan chemotherapy.
Juang, Vivian; Chang, Chih-Hsien; Wang, Chen-Shen; Wang, Hsin-Ell; Lo, Yu-Li · Preclinical (In Vitro + Animal)
RPEP-04275 · 2019All four monoclonal antibodies targeting the CGRP pathway — eptinezumab, erenumab, fremanezumab, and galcanezumab — showed positive results for preventing both episodic and chronic migraine across phase II and III clinical trials. This review of 32 eligible randomized controlled trials collectively demonstrated that blocking CGRP signaling is an effective preventive strategy for migraine.
The review noted that phase III trials were also underway for cluster headache prevention, though results were still pending at the time. The authors flagged the importance of monitoring cardiovascular effects of long-term CGRP blockade, since CGRP plays a role in blood vessel dilation and cardiovascular protection.
Khan, Sabrina; Olesen, Astrid; Ashina, Messoud · Systematic Review
RPEP-04276 · 2019TatBim peptide and miR-34a formed nanocomplexes approximately 250 nm in diameter that were efficiently internalized by cancer cells. However, increasing RNA content paradoxically reduced apoptotic activity, likely because the tightly bound complex couldn't release its components inside the cell.
Attaching a photosensitizer to TatBim and applying light irradiation significantly rescued the apoptotic activity by promoting endosomal escape — allowing the peptide and RNA to disperse into the cytoplasm where they can act. Control experiments (substituting TatBim with Lipofectamine, or miR-34a with scrambled siRNA) confirmed that both the peptide and the microRNA contributed independently to the cancer cell killing effect.
Kim, Hyungjin; Kitamatsu, Mizuki; Ohtsuki, Takashi ·
RPEP-04287 · 2019Selank at 0.3 mg/kg/day for 7 days intraperitoneally produced a cognitive-stimulating effect in 9-month-old control rats (p<0.05) and prevented ethanol-induced memory and attention disturbances during alcohol withdrawal (p<0.01). In ex vivo brain tissue analysis, Selank prevented the ethanol-induced increase in BDNF content in both the hippocampus and frontal cortex (p<0.05). The protective effect on memory was assessed using the object recognition test, which measures both recognition memory and attention.
Kolik, L G; Nadorova, A V; Antipova, T A; Kruglov, S V; Kudrin, V S; Durnev, A D ·
RPEP-04288 · 2019Different casein processing methods produce different peptide profiles during digestion and different levels of GLP-1 release. Micellar casein concentrate (MCC) had higher digestibility and induced greater GLP-1 secretion from enteroendocrine GLUTag cells than sodium caseinate mixed with whey protein isolate (SCN + WPI). A specific peptide — GPVRGPFPIIV — was identified only in MCC digesta and confirmed to stimulate GLP-1 release when chemically synthesized and tested.
Komatsu, Yosuke; Wada, Yasuaki; Izumi, Hirohisa; Shimizu, Takashi; Takeda, Yasuhiro; Hira, Tohru; Hara, Hiroshi ·
RPEP-04290 · 2019BPC 157 (10 µg/kg, given orally) counteracted the inhibitory effects of aspirin, clopidogrel, and cilostazol on platelet aggregation across multiple activation pathways:
- Reversed arachidonic acid-induced aggregation inhibition (vs. all three drugs)
- Reversed arachidonic acid/PGE1 aggregation inhibition (vs. cilostazol)
- Reversed ADP-induced aggregation inhibition (vs. clopidogrel)
- Reversed collagen-induced aggregation inhibition (vs. clopidogrel)
Critically, BPC 157 had no effect on extrinsic/intrinsic hemostasis or fibrin clot parameters (EXTEM, INTEM, FIBTEM measurements were unchanged), demonstrating specificity for platelet function rescue.
Konosic, Sanja; Petricevic, Mate; Ivancan, Visnja; Konosic, Lucija; Goluza, Eleonora; Krtalic, Branimir; Drmic, Domagoj; Stupnisek, Mirjana; Seiwerth, Sven; Sikiric, Predrag ·
RPEP-04291 · 2019Treatment of A375 melanoma cells with an ERAP1 inhibitor altered the presentation of approximately half of the 3,204 identified peptides displayed on MHC class I molecules, including about one third of peptides predicted to bind tightly to MHC-I. The inhibitor did not reduce cell-surface MHC-I expression levels.
The most surprising finding was that ERAP1 inhibition actually improved the average predicted MHC-I binding affinity of displayed peptides. This occurred because the enzyme's normal activity was destroying many high-quality potential epitopes (9–12 amino acid peptides) while allowing suboptimal long peptides to persist. Blocking ERAP1 reduced presentation of these suboptimal long peptides and increased presentation of many high-affinity shorter peptides — essentially improving the immunogenicity of the tumor cells.
Koumantou, Despoina; Barnea, Eilon; Martin-Esteban, Adrian; Maben, Zachary; Papakyriakou, Athanasios; Mpakali, Anastasia; Kokkala, Paraskevi; Pratsinis, Harris; Georgiadis, Dimitris; Stern, Lawrence J; Admon, Arie; Stratikos, Efstratios ·
RPEP-04293 · 2019Across seven cardiovascular outcome trials (ELIXA, LEADER, SUSTAIN-6, EXSCEL, Harmony Outcomes, REWIND, and PIONEER 6) totaling 56,004 participants, GLP-1 receptor agonists reduced major adverse cardiovascular events (MACE) by 12% (HR 0.88, 95% CI 0.82–0.94, p<0.0001).
Breaking down the components: cardiovascular death was reduced by 12% (HR 0.88, p=0.003), stroke by 16% (HR 0.84, p<0.0001), and myocardial infarction by 9% (HR 0.91, p=0.043). All-cause mortality fell by 12% (HR 0.88, p=0.001), heart failure hospitalization by 9% (HR 0.91, p=0.028), and a composite kidney outcome by 17% (HR 0.83, p<0.0001), driven primarily by reduced urinary albumin excretion. No increased risk of severe hypoglycemia, pancreatitis, or pancreatic cancer was observed.
Kristensen, Søren L; Rørth, Rasmus; Jhund, Pardeep S; Docherty, Kieran F; Sattar, Naveed; Preiss, David; Køber, Lars; Petrie, Mark C; McMurray, John J V ·
RPEP-04310 · 2019The L6 cell-penetrating peptide (sequence RRWQWR) derived from bovine lactoferricin noncovalently bound to quantum dots to form stable complexes. These complexes entered human lung cancer cells most efficiently at a nitrogen/phosphate ratio of 60, using an endocytic pathway.
Critically, L6 and L6/QD complexes showed no cytotoxicity, and the industrial preservative BIT did not enhance L6-mediated delivery, distinguishing its uptake mechanism from other cell-penetrating peptides.
Lee, Han-Jung; Huang, Yue-Wern; Aronstam, Robert S ·
RPEP-04311 · 2019Fish scale collagen peptide NS (CPNS) was characterized with Gly-Pro identified as a representative bioactive dipeptide. Key findings:
- In cell culture: CPNS reduced MMP-1 (collagen-degrading enzyme) production and increased type 1 procollagen synthesis in human dermal fibroblasts
- In rats: Oral CPNS dramatically increased plasma concentrations of Gly-Pro and Pro-Hyp, confirming bioavailability
- In 12-week hairless mouse study: Oral CPNS significantly attenuated UVB-induced wrinkle formation, reduced transepidermal water loss, decreased epidermis thickening, and increased skin hydration compared to UV-exposed controls
Lee, Hyun-Jun; Jang, Hye-Lim; Ahn, Dong-Kyu; Kim, Hun-Jung; Jeon, Hee Young; Seo, Dae Bang; Lee, Ji-Hae; Choi, Jin Kyu; Kang, Seok-Seong ·
RPEP-04317 · 2019Tachykinins (NKA, NKB, and substance P) participate in the central control of GnRH release through neuronal circuits that activate Kiss1 neurons and synchronize their activity within the arcuate nucleus. Their roles extend across the full spectrum of reproductive function: regulating the pulsatile pattern of GnRH release, determining the timing of puberty onset, and controlling the preovulatory LH surge in females. The review synthesizes evidence that tachykinins are critical for all major aspects of fertility attainment and maintenance.
Leon, Silvia; Navarro, Víctor M ·
RPEP-04318 · 2019Mice lacking the growth hormone-releasing hormone (GHRH) gene showed increased sensitivity to both pain and inflammation compared to normal mice. GHRH knockout mice had decreased response latency on the hot plate test (faster pain response), increased licking/biting during the formalin test (especially in the inflammatory phase), and significantly greater colonic inflammation after DSS treatment. Inflammatory markers — PGE2, 8-iso-PGF2α, COX-2, and TNF-α — were all elevated more dramatically in knockout mice, both in vivo and ex vivo.
Leone, Sheila; Chiavaroli, Annalisa; Recinella, Lucia; Orlando, Giustino; Ferrante, Claudio; Marconi, Guya Diletta; Gasparo, Irene; Bitto, Alessandra; Salvatori, Roberto; Brunetti, Luigi ·
RPEP-04321 · 2019The oxidation-responsive nanoparticles (AON) containing the annexin A1-mimetic peptide Ac2-26 achieved site-specific drug release at inflamed colon tissue by responding to elevated reactive oxygen species (ROS) levels. The nanoparticle shell protected the peptide from degradation in the harsh gastrointestinal environment.
Mechanistically, AON decreased expression of proinflammatory mediators, reduced inflammatory cell infiltration, promoted the cleanup of dying neutrophils (efferocytosis), and shifted macrophages toward an anti-inflammatory state. Therapeutically, this translated to reduced inflammation symptoms, accelerated intestinal mucosal wound healing, reshaped gut microbiota composition, and increased short-chain fatty acid production. Oral delivery showed an excellent safety profile.
Li, Chenwen; Zhao, Yang; Cheng, Juan; Guo, Jiawei; Zhang, Qixiong; Zhang, Xiangjun; Ren, Jiong; Wang, Fengchao; Huang, Jun; Hu, Houyuan; Wang, Ruibing; Zhang, Jianxiang ·
RPEP-04324 · 2019Thymosin β4 dose-dependently increased the viability of neural stem/progenitor cells (NSPCs) exposed to hydrogen peroxide-induced oxidative stress. The peptide reversed multiple markers of injury: it normalized intracellular calcium concentrations, reduced lactate dehydrogenase release (a marker of cell damage), decreased apoptosis (programmed cell death), lowered reactive oxygen species (ROS) production, and reduced pro-inflammatory cytokine levels.
The mechanism was identified as suppression of the TLR4/MyD88 signaling pathway. Thymosin β4 reduced expression of both TLR4 and MyD88 in stressed cells, and a specific TLR4/MyD88 pathway inhibitor replicated all of thymosin β4's protective effects — confirming this pathway as the key mediator of the peptide's neuroprotective action.
Li, Hongwei; Wang, Yonggang; Hu, Xuchang; Ma, Bing; Zhang, Haihong ·
RPEP-04326 · 2019The engineered RMTQ peptide demonstrated enhanced cytoplasmic delivery, greater reduction of pro-inflammatory factors, and better efficacy than the unmodified QAW peptide in adjuvant-induced arthritis mice. RMTQ's anti-inflammatory efficacy matched dexamethasone (DEX), the standard steroid treatment, while showing a superior safety profile.
The modular design incorporated four functional elements: QAW (the anti-inflammatory tripeptide), a cell-penetrating peptide for intracellular delivery, an MMP-2/9-cleavable linker for inflammation-responsive activation, and an RGD targeting peptide for inflammation site homing.
Li, Na; Qiao, Yonghui; Xue, Lingping; Xu, Shiqi; Zhang, Nan ·