RPEP-04713 · 2020In a rat model of bronchial asthma, acupuncture altered the levels of several neuropeptides in lung tissue. Asthmatic rats showed decreased vasoactive intestinal peptide (VIP) and cAMP/cGMP ratios alongside increased substance P (SP), neurokinin A (NKA), and neurokinin B (NKB). Acupuncture treatment partially reversed these changes — increasing cAMP/cGMP while decreasing NKA, NKB, and SP — and improved lung tissue pathology.
When the adrenal glands were removed before acupuncture, the peptide-level improvements were blunted, suggesting that acupuncture's effects on airway neuropeptides depend partly on intact adrenal (glucocorticoid) function.
Chen, Yujuan; Gao, Yanlu; Lu, Wenwen; Gao, Wei · Animal Study
RPEP-04723 · 2020In the POMC deficiency trial (n=10): 80% of participants achieved at least 10% weight loss at approximately 1 year. Mean hunger score reduction was -27.1% (p=0.0005).
In the LEPR deficiency trial (n=11): 45% of participants achieved at least 10% weight loss. Mean hunger score reduction was -43.7% (p<0.0001).
During the placebo-controlled withdrawal phase, symptoms returned when patients were switched to placebo, confirming the drug's direct effect. Most common adverse events were injection site reactions and hyperpigmentation (skin darkening). No serious treatment-related adverse events occurred in either trial.
Clément, Karine; van den Akker, Erica; Argente, Jesús; Bahm, Allison; Chung, Wendy K; Connors, Hillori; De Waele, Kathleen; Farooqi, I Sadaf; Gonneau-Lejeune, Julie; Gordon, Gregory; Kohlsdorf, Katja; Poitou, Christine; Puder, Lia; Swain, James; Stewart, Murray; Yuan, Guojun; Wabitsch, Martin; Kühnen, Peter ·
RPEP-04724 · 2020B. subtilis colonization provided comprehensive protection in multiple C. elegans Alzheimer's models:
- Delayed aging and neuronal deterioration in wild-type worms compared to E. coli-fed controls
- Alleviated amyloid-β-induced paralysis in transgenic strains CL2120 (Aβ3-42) and GMC101 (Aβ1-42)
- Protected against behavioral deficits including impaired chemotaxis and decreased body bends in CL2355 worms with pan-neuronal Aβ1-42 expression
- Restored lifespan of Aβ-expressing worms to levels similar to wild-type worms on standard E. coli diet
Critically, B. subtilis strains deficient in quorum-sensing peptide (CSF) synthesis or gut biofilm formation lost their anti-AD effects, demonstrating that these bacterial peptide-dependent processes are essential for the neuroprotective benefits.
Cogliati, Sebastián; Clementi, Victoria; Francisco, Marcos; Crespo, Cira; Argañaraz, Federico; Grau, Roberto ·
RPEP-04728 · 2020Substance P and neurotensin both induced dose-dependent serotonin release from rat peritoneal mast cells, while neuromedin-N did not. Two natural α,β-unsaturated lactones — dehydroleucodine and xanthatin — inhibited this neuropeptide-induced serotonin release, while a third compound (3-benzyloxymethyl-5H-furan-2-one) did not.
Notably, dehydroleucodine and xanthatin showed higher inhibitory potency than the reference anti-allergy compounds ketotifen and sodium chromoglycate when mast cells were pretreated before neuropeptide exposure. This represents the first evidence that these compounds can block neuropeptide-specific mast cell activation, distinct from their previously known effects on other degranulation pathways.
Coll, Roberto Carlos; Vargas, Patricia María; Mariani, María Laura; Penissi, Alicia Beatriz ·
RPEP-04729 · 2020In 33 healthy men, kisspeptin enhanced limbic brain activity (amygdala, caudate, putamen, thalamus) to olfactory and visual attraction cues, enhanced penile tumescence, and increased attraction scores.
Comninos, Alexander N; Demetriou, Lysia; Wall, Matthew B; Shah, Amar J; Clarke, Sophie A; Narayanaswamy, Shakunthala; Neher, Asija; Dodge, John A; Bloom, Stuart R; Dhillo, Waljit S · Human Rct
RPEP-04731 · 2020Four three-finger toxin peptides from N. nigricollis venom showed cytotoxic activity. Cytotoxin-1N was most potent: LC50 = 0.8 μM (A549 lung cancer), 7 μM (MDA-MB-231 breast cancer), 9 μM (HT-29 colorectal cancer). However, all peptides were also cytotoxic to normal HUVEC endothelial cells (LC50 2-22 μM), and cytotoxin-2N was moderately hemolytic (LC50 45 μM). Separately, two phospholipase A2 isoforms stimulated insulin release approximately 6-fold from BRIN-BD11 beta-cells at 1 μM — a non-cytotoxic concentration.
Conlon, J M; Attoub, Samir; Musale, Vishal; Leprince, Jérôme; Casewell, Nicholas R; Sanz, Libia; Calvete, Juan J ·
RPEP-04732 · 2020Defensins — one of the largest families of antimicrobial peptides — do far more than kill pathogens. This review reveals that defensins also function as immunomodulators (shaping immune responses) and immune cell attractors (recruiting defensive cells to infection sites). These peptides are found across animals, plants, and fungi, and can be expressed either constantly or ramped up in response to infection.
The review maps the signaling pathways that control defensin gene expression, showing how pattern-recognition receptors detect pathogen-associated molecular patterns (PAMPs) and trigger transcription factor activation to produce defensins. Understanding these trigger mechanisms may reveal additional defensin functions beyond what's currently known.
Contreras, Gabriela; Shirdel, Iman; Braun, Markus Santhosh; Wink, Michael · Review
RPEP-04735 · 2020DAT-GHSR mice (ghrelin receptor expression limited to dopamine neurons) showed: (1) c-Fos activation in dopamine-containing brain areas after ghrelin treatment, similar to wild-type mice; (2) normal anticipatory activity to scheduled high-fat diet exposure; (3) full binge-like high-fat intake comparable to wild-type mice. However, they did NOT show: increased food intake or locomotor activity in response to systemic or central ghrelin administration. GHSR-deficient mice showed impaired anticipatory activity and binge eating. Conclusion: GHSR in dopamine neurons is sufficient for hedonic high-fat eating but insufficient for ghrelin's homeostatic orexigenic effects.
Cornejo, María Paula; Barrile, Franco; Cassano, Daniela; Aguggia, Julieta Paola; García Romero, Guadalupe; Reynaldo, Mirta; Andreoli, María Florencia; De Francesco, Pablo Nicolás; Perello, Mario ·
RPEP-04741 · 2020Researchers designed four double-stapled peptides based on the ACE2 receptor helix that SARS-CoV-2 uses to enter human cells. Three of four showed potent antiviral activity with IC50 values of 1.9–4.1 μM in ACE2-overexpressing cells. The most effective peptide, NYBSP-1, completely prevented viral damage at 17.2 μM against authentic SARS-CoV-2. The stapled peptides achieved 50–94% helicity versus only 19% for the linear control, and showed no cytotoxicity. Lead peptide NYBSP-4 demonstrated a plasma half-life exceeding 289 minutes.
Curreli, Francesca; Victor, Sofia M B; Ahmed, Shahad; Drelich, Aleksandra; Tong, Xiaohe; Tseng, Chien-Te K; Hillyer, Christopher D; Debnath, Asim K ·
RPEP-04743 · 2020MOTS-c, a mitochondrial-derived peptide, shows opposite age-related patterns in blood versus muscle. Circulating MOTS-c in plasma decreased with age, but muscle MOTS-c expression was approximately 1.5 times higher in older (70–81 years) and middle-aged (45–55 years) men compared to young men (18–30 years).
The increase in muscle MOTS-c was associated with slow-type muscle fiber markers, consistent with the well-known fast-to-slow fiber type transition that occurs with aging. In older men, higher muscle MOTS-c was associated with better muscle quality (maximal leg-press strength relative to thigh cross-sectional area).
The study also found evidence that MOTS-c transcription may be regulated independently of the full-length 12S rRNA gene it sits within, and that its expression in human muscle is not linked to antioxidant response element (ARE) genes as previously seen in cell culture.
D'Souza, Randall F; Woodhead, Jonathan S T; Hedges, Christopher P; Zeng, Nina; Wan, Junxiang; Kumagai, Hiroshi; Lee, Changhan; Cohen, Pinchas; Cameron-Smith, David; Mitchell, Cameron J; Merry, Troy L · Observational
RPEP-04746 · 2020In 72 rats divided into 6 treatment groups, dental bleaching increased inflammation and expression of the neuropeptides substance P and calcitonin gene-related peptide (CGRP) in pulp nerve fibers. These markers decreased naturally over 48 hours across all bleaching groups.
Rats treated with a topical desensitizing agent (potassium nitrate/sodium fluoride) before bleaching showed significantly better outcomes within 24 hours compared to untreated bleached animals. Ibuprofen administered before and after bleaching (and every 12 hours thereafter) did not show the same positive effects on neuropeptide expression, suggesting the desensitizing gel more effectively targets nerve-level inflammation.
da Silva, Livia Maria Alves Valentim; Cintra, Luciano Tavares Angelo; Gallinari, Marjorie de Oliveira; Benetti, Francine; Rahal, Vanessa; Ervolino, Edilson; de Alcântara, Sibele; Briso, André Luiz Fraga ·
RPEP-04747 · 2020Researchers rigorously characterized a peptide-based nanovaccine candidate for HIV/SIV prevention consisting of chitosan/dextran sulfate nanoparticles loaded with twelve SIV peptide antigens. Using a quality-by-design approach, they validated particle size characterization across three complementary techniques and confirmed inter-batch reproducibility across three independent laboratories.
The nanoformulation demonstrated long-term stability and scalable manufacturing. Combined with previously reported in vivo efficacy in macaque models, these results position the peptide nanovaccine as a viable candidate for advancement to clinical trials.
Dacoba, Tamara G; Ruiz-Gatón, Luisa; Benito, Ana; Klein, Marlène; Dupin, Damien; Luo, Ma; Menta, Mathieu; Teijeiro-Osorio, Desirée; Loinaz, Iraida; Alonso, María J; Crecente-Campo, José ·
RPEP-04748 · 2020Through transcriptomic analysis comparing the growth phase (anagen) and resting phase (telogen) of cashmere goat hair follicles, researchers identified Thymosin β4 (Tβ4) as a key differentially expressed gene with higher expression during the active growth phase.
Functional validation showed that overexpressing Tβ4 promoted the proliferation of secondary hair follicle dermal papilla cells (SHF-DPCs), while silencing Tβ4 inhibited their proliferation. This establishes Tβ4 as a functional regulator of hair follicle cell growth.
Dai, Bai; Hao, Fei; Xu, Teng; Zhu, Bing; Ren, Li-Qing; Han, Xiao-Yu; Liu, Dong-Jun ·
RPEP-04750 · 2020When human colonic mucosal tissue was exposed to hemokinin-1 (HK-1) at 0.1 μM for 4 hours, it significantly increased both gene expression and release of multiple inflammatory mediators: MCP-1, MIP-1α, MIP-1β, RANTES, TNF-α, IL-1β, and IL-6.
Substance P (SP) at the same concentration produced comparable effects on most mediators but notably did not affect MCP-1 or RANTES — indicating HK-1 has a broader pro-inflammatory profile than SP in the human colon.
Both NK1 receptor antagonist SR140333 and NK2 receptor antagonist SR48968 (each at 0.1 μM) separately inhibited these inflammatory responses, demonstrating that both receptor types mediate the effects. This dual-receptor involvement was a novel finding and suggests HK-1 may also signal through additional tachykinin-preferring receptors.
Dai, Liying; Perera, D Shevy; Burcher, Elizabeth; Liu, Lu ·
RPEP-04751 · 2020The cancer peptide vaccine S-588410 — containing five HLA-A*24:02-restricted peptides derived from cancer testis antigens — successfully induced tumor-specific immune responses in all 15 esophageal cancer patients. After vaccination, tumor tissue showed increased densities of CD8+ T-cells, CD8+ granzyme B+ cells (indicating active killing), and CD8+ PD-1+ cells. PD-L1 expression also increased in the tumor microenvironment.
Critically, the same peptide-specific T-cell receptor sequences were found in both blood and tumor tissue after vaccination, confirming that the vaccine-induced killer T-cells actually infiltrated the tumors. The upregulation of PD-1 and PD-L1 after vaccination suggests that combining S-588410 with checkpoint inhibitors (anti-PD-1/PD-L1 antibodies) could further enhance its anti-cancer effect.
Daiko, H; Marafioti, T; Fujiwara, T; Shirakawa, Y; Nakatsura, T; Kato, K; Puccio, I; Hikichi, T; Yoshimura, S; Nakagawa, T; Furukawa, M; Stoeber, K; Nagira, M; Ide, N; Kojima, T · Clinical Trial
RPEP-04754 · 2020This review catalogs the major barriers peptide and protein drugs face when taken orally — mucus, digestive enzymes, and the intestinal cell lining — and the pharmaceutical strategies being used to overcome them. Key approaches include: co-administration with protease inhibitors to prevent enzymatic breakdown, PEGylation and mucoadhesive polymers to extend gut residence time, cell-penetrating peptides to cross the intestinal barrier, nanoparticle carriers (liposomes, microspheres, nanospheres) for protected transport, and enteric coatings to survive stomach acid. The review also covers formulations that have reached clinical approval.
Dan, Nirnoy; Samanta, Kamalika; Almoazen, Hassan · Review
RPEP-04756 · 2020Between 2015 and 2019, approximately 500 new natural antimicrobial peptides (AMPs) were discovered and registered in the antimicrobial peptide database. This review highlights the most notable discoveries, including: teixobactin (a cell-wall-inhibiting peptide antibiotic), darobactin (which targets outer membrane protein assembly in Gram-negative bacteria), cOB1 (a sex pheromone from gut bacteria that kills multidrug-resistant E. faecalis at picomolar concentrations), urumin (a frog peptide that specifically inhibits H1 influenza A virus), and TLN-58 (a newly discovered alternative human cathelicidin peptide that proves one gene can produce multiple antimicrobial peptides).
The review also highlights the expanding functional roles of AMPs beyond infection-fighting — including a fly peptide called nemuri that induces sleep, linking immune defense to sleep regulation.
Dang, Xiangli; Wang, Guangshun · Review
RPEP-04758 · 2020Since the first activatable cell-penetrating peptide was reported in 2004, multiple activation strategies have been developed to control when and where CPPs become active. These include enzyme-triggered activation (using proteases overexpressed in diseased tissue), pH-responsive activation, light-triggered activation, and other environmental triggers. The review provides a comprehensive overview of these strategies, noting that while significant progress has been made, challenges remain in achieving the specificity and efficiency needed for clinical translation.
de Jong, Heleen; Bonger, Kimberly M; Löwik, Dennis W P M ·
RPEP-04759 · 2020Using computer simulations, researchers mapped how novel cyclic peptide ghrelin analogs (A228 and A233) bind to the ghrelin receptor (GHS-R1a). Despite having different structures from natural ghrelin and GHRP-6, all four peptides share a common binding mode: their N-terminal end interacts with a specific amino acid (E124) on the receptor, and a nearby aromatic residue docks into an aromatic cluster (F279, F309, F312).
From this analysis, they proposed a preliminary pharmacophore model — the minimum molecular features needed for ghrelin receptor activation: a positively charged amine and an aromatic ring separated by approximately 0.79 nm. This pharmacophore could serve as a template for designing new ghrelin receptor drugs.
Molecular dynamics simulations over 100 nanoseconds confirmed the stability of these peptide-receptor complexes in a realistic cell membrane environment.
de la Nuez Veulens, Ania; Rodríguez Fernández, Rolando E; Álvarez Ginarte, Yoanna M; Montero Cabrera, Luis A · Computational Study
RPEP-04764 · 2020BeKm-1, a scorpion venom peptide that selectively blocks hERG potassium channels from the outside of the cell, successfully reproduced key features of drug-induced long QT syndrome in human stem cell-derived cardiomyocytes. The peptide delayed heart cell repolarization, induced early afterdepolarizations (abnormal electrical events), and reduced spontaneous beating rate, calcium transients, and contraction frequency — all hallmarks of arrhythmia risk.
Because BeKm-1 blocks hERG from the extracellular face (unlike most drugs that block from inside), it serves as a unique reference compound for cardiac safety testing and as a modifiable molecular platform for designing new hERG-targeting therapeutics.
De Waard, Stephan; Montnach, Jérôme; Ribeiro, Barbara; Nicolas, Sébastien; Forest, Virginie; Charpentier, Flavien; Mangoni, Matteo Elia; Gaborit, Nathalie; Ronjat, Michel; Loussouarn, Gildas; Lemarchand, Patricia; De Waard, Michel · Laboratory
RPEP-04765 · 2020After 17% body weight loss maintained at one year, reduced-obese adults showed increased hunger ratings and higher ghrelin secretion (both basal and postprandial) compared to their pre-weight-loss baseline. However, these appetite markers were not different from those of body-composition-matched nonobese controls, indicating normalization rather than compensatory overshoot.
Postprandial concentrations of active GLP-1, total peptide YY, and cholecystokinin remained lower in individuals with obesity at all time points compared to nonobese controls — both before and after weight loss. This suggests that blunted satiety peptide secretion is a feature of obesity itself rather than a consequence of weight loss.
DeBenedictis, Julia Nicole; Nymo, Siren; Ollestad, Karoline Haagensli; Boyesen, Guro Akersveen; Rehfeld, Jens Frederik; Holst, Jens Juul; Truby, Helen; Kulseng, Bard; Martins, Catia ·
RPEP-04767 · 2020Ketogenic diets prevent the increase in ghrelin secretion that normally accompanies weight loss, while also reducing hunger and preventing hunger increases. The exact threshold of ketosis required for appetite suppression has not been established.
Exogenous ketone esters showed concentration-dependent effects on food intake and body weight in rodent models, with a threshold effect appearing when ketone esters provided 30% of total dietary energy. In a human study, acute consumption of a ketone ester drink reduced feelings of hunger and increased satiety compared to a dextrose (sugar) drink. The mechanisms mediating ketosis-induced appetite suppression remain to be fully elucidated.
Deemer, Sarah E; Plaisance, Eric P; Martins, Catia ·
RPEP-04768 · 2020Adding liraglutide 1.8 mg daily to insulin pump therapy in overweight adults with type 1 diabetes produced three significant benefits over 26 weeks compared to placebo: HbA1c dropped by 0.5% (vs. a 0.2% increase with placebo, p<0.001), body weight decreased by 6.3 kg (p<0.001), and total insulin dose fell by 8 units/day (16% reduction, p=0.008). Time in the target glucose range (71-180 mg/dL) increased without raising the risk of hypoglycemia.
Dejgaard, Thomas F; Schmidt, Signe; Frandsen, Christian S; Vistisen, Dorte; Madsbad, Sten; Andersen, Henrik U; Nørgaard, Kirsten · Rct
RPEP-04769 · 2020Across 11 high-quality RCTs (n=4,402), compared to placebo:
- Monthly migraine days reduced by 1.44 days (WMD: -1.44; 95% CI: -1.68 to -1.19)
- Acute migraine-specific medication days reduced by 1.28 days (WMD: -1.28; 95% CI: -1.66 to -0.90)
- 50% responder rate improved by 51% (RR: 1.51; 95% CI: 1.37 to 1.66)
- Adverse events and withdrawal rates due to AEs were not significantly different from placebo
- Subgroup analysis showed similar efficacy and safety for erenumab, fremanezumab, and galcanezumab individually
Deng, Hong; Li, Gai-Gai; Nie, Hao; Feng, Yang-Yang; Guo, Guang-Yu; Guo, Wen-Liang; Tang, Zhou-Ping ·
RPEP-04770 · 2020The research team deployed their NetH2pan prediction tool combined with advanced proteomics to identify five unique MHC class I/PyMT peptide epitopes in the MMTV-PyMT transgenic breast cancer model. These tumor-specific peptides were confirmed to be naturally presented on the surface of primary tumors by MHC class I molecules.
T cell immunogenicity of all five epitopes was validated — meaning the immune system could recognize and respond to these peptides. A DNA vaccine encoding a truncated PyMT protein generated CD8+ T cell responses targeting these specific MHC class I/peptide complexes and prevented tumor development in the metastatic breast cancer model.
DeVette, Christa I; Gundlapalli, Harika; Lai, Shu-Chin Alicia; McMurtrey, Curtis P; Hoover, Ashley R; Gurung, Hem R; Chen, Wei R; Welm, Alana L; Hildebrand, William H ·
RPEP-04771 · 2020The review identifies three primary peptide-based and molecular strategies for mitochondria-specific drug delivery:
1. Mitochondrial targeting signal peptides (MTS): Short peptide sequences that exploit the cell's natural protein import machinery to deliver therapeutic cargo directly into mitochondria.
2. Cell-penetrating peptides (CPPs): Peptides that can cross cell membranes and carry attached drug molecules into cells and their organelles, including mitochondria.
3. Lipophilic cations: Positively charged molecules that accumulate in mitochondria driven by the mitochondrial membrane potential.
The review notes that conjugating these targeting ligands to therapeutic molecules enhances their effectiveness, and that nanoparticle-based delivery systems can address remaining challenges related to drug solubility and selectivity.
Dhanasekaran, Sugapriya; Venugopal, Divya; Al-Dayan, Noura; Ravinayagam, Vijaya; Mohammed, Arif Ahmed ·
RPEP-04773 · 2020When a defensin-sensitive adenovirus serotype was passaged in the presence of human defensin, mutations accumulated in the hexon protein — the major capsid protein — rather than in the vertex proteins previously identified as important for defensin antiviral activity.
Infection and biochemical assays revealed that defensins interact with all major capsid proteins, creating a balance between two opposing effects: increased cell binding (which could enhance infection) and a downstream block in intracellular trafficking (which inhibits infection). The net outcome of infection depends on which effect dominates. This demonstrates that defensins impose genuine selective pressure during fecal-oral transmission, driving viral evolution and explaining why closely related viruses can have very different infection outcomes.
Diaz, Karina; Hu, Ciara T; Sul, Youngmee; Bromme, Beth A; Myers, Nicolle D; Skorohodova, Ksenia V; Gounder, Anshu P; Smith, Jason G ·
RPEP-04774 · 2020Across 5 RCTs with 2,445 participants, liraglutide added to insulin in type 1 diabetes produced modest HbA1c reductions (up to -0.24% with 1.8 mg dose), significant weight loss (up to 4.87 kg), and decreased total daily insulin requirements — mainly bolus insulin.
Severe hypoglycemia was non-significantly reduced (OR=0.80), but gastrointestinal side effects increased substantially: nausea odds were 4.7 times higher and vomiting 2.5 times higher. Heart rate also increased. No link to diabetic ketoacidosis or malignancies was found.
Dimitrios, Patoulias; Michael, Doumas; Vasilios, Kotsis; Konstantinos, Stavropoulos; Konstantinos, Imprialos; Ioanna, Zografou; Konstantinos, Petidis; Spyridon, Bakatselos; Asterios, Karagiannis · Meta Analysis
RPEP-04775 · 2020Immunohistochemistry and confocal microscopy revealed altered expression of substance P and CGRP in both affected and unaffected scalp skin from LPP and FFA patients compared to controls. However, ELISA quantification showed opposite patterns in LPP versus FFA — suggesting different pathogenic mechanisms despite similar histopathological features. Notably, inflammation was present in clinically unaffected scalp skin in both diseases, indicating these may be more generalized scalp processes than previously thought.
Doche, Isabella; Wilcox, George L; Ericson, Marna; Valente, Neusa S; Romiti, Ricardo; McAdams, Brian D; Hordinsky, Maria K ·
RPEP-04776 · 2020The spray drying process achieved yields up to 84.67% for trehalose and >83.24% for glucagon and glucagon-trehalose formulations. A psychrometric process model identified optimal operating conditions that significantly reduced residual moisture and particle agglomeration compared to non-optimal drying. Critically, extensive peptide aggregation or fibrillation (a common problem with glucagon) was not observed in the spray-dried product, confirming the process preserved peptide integrity.
Doerr, Frederik J S; Burns, Lee J; Lee, Becky; Hinds, Jeremy; Davis-Harrison, Rebecca L; Frank, Scott A; Florence, Alastair J ·
RPEP-04778 · 2020The review synthesizes evidence showing thymosin alpha-1 has clinical applications across multiple domains: treatment of immunocompromised states and malignancies, enhancement of vaccine responses, and reduction of morbidity and mortality in sepsis and infections. For COVID-19 specifically, studies suggest thymosin alpha-1 could repair lymphocytic immunity damage while preventing excessive T cell activation — addressing both the immune suppression and hyperactivation that characterize severe COVID-19.
Dominari, Asimina; Hathaway Iii, Donald; Pandav, Krunal; Matos, Wanessa; Biswas, Sharmi; Reddy, Gowry; Thevuthasan, Sindhu; Khan, Muhammad Adnan; Mathew, Anoopa; Makkar, Sarabjot Singh; Zaidi, Madiha; Fahem, Michael Maher Mourad; Beas, Renato; Castaneda, Valeria; Paul, Trissa; Halpern, John; Baralt, Diana ·
RPEP-04783 · 2020Nine types of injectable combination therapies (ICTs) are currently available for diabetes, including combinations of conventional human insulin, insulin analogs, insulin coformulations, and insulin/GLP-1 receptor agonist combinations. Meta-analysis data showed no significant differences in HbA1c reduction, hypoglycemia, weight change, or daily insulin dose between ICTs and basal-bolus regimens. ICTs are recommended by all international guidelines for treatment intensification, offering reduced daily needle-prick count and improved long-term compliance.
Dutta, Deep; Khandelwal, Deepak; Kalra, Sanjay ·
RPEP-04786 · 2020The review synthesizes several key findings about PYY in IBS:
• PYY concentration and PYY-producing endocrine cell density are decreased in both the colon and rectum of IBS patients
• PYY cell density in the ileum (small intestine) remains unchanged
• The reduced PYY cells may result from decreased stem cell differentiation toward endocrine cell lineages
• PYY regulates intestinal motility, secretion, absorption, and visceral sensitivity by modulating serotonin release
• PYY abnormalities may therefore contribute to the intestinal dysmotility and visceral hypersensitivity characteristic of IBS
• A low-FODMAP diet restores PYY cell density in the large intestine and improves abdominal symptoms in IBS patients
El-Salhy, Magdy; Hatlebakk, Jan Gunnar; Hausken, Trygve ·
RPEP-04793 · 2020The study presents a computational pipeline combining multiple machine learning methods (SVM, random forest classifiers, and neural networks) to predict amphiphilic cell-penetrating peptide sequences from the human Ki-67 protein. Ki-67 naturally acts as a biosurfactant — a steric and electrostatic barrier against chromosome collapse during cell division — making it a unique source for amphiphilic peptide building blocks. The predicted peptides are designed to spontaneously form self-assembled nanocarriers with enhanced cellular uptake and inherent low immunogenicity.
Feger, Guillaume; Angelov, Borislav; Angelova, Angelina ·
RPEP-04795 · 2020Cyclo[Pro-Sar-Phe-d-Phe] was rationally designed based on X-ray and NMR structures of related macrocyclic tetrapeptides. Key pharmacological findings:
- **Orally bioavailable**: The peptide produced antinociception (pain relief) and kappa opioid receptor (KOR) antagonism when given orally in mice.
- **Anti-relapse effects**: Oral administration blocked both stress-induced and drug-induced reinstatement of cocaine and morphine conditioned place preference — the gold-standard preclinical model for relapse.
- **Reduced side effects**: The peptide showed a decreased side-effect profile compared to morphine.
- **Mixed opioid profile**: It acts as an agonist at some opioid receptors while antagonizing kappa opioid receptors, a profile thought to be ideal for treating addiction.
Ferracane, Michael J; Brice-Tutt, Ariana C; Coleman, Jeremy S; Simpson, Grant G; Wilson, Lisa L; Eans, Shainnel O; Stacy, Heather M; Murray, Thomas F; McLaughlin, Jay P; Aldrich, Jane V ·
RPEP-04801 · 2020Dopaminergic neurons derived from human induced pluripotent stem cells were encapsulated in self-assembling peptide nanofiber scaffolds (SAPNS) based on the peptide RADA16-I. The encapsulated neurons expressed mature neuronal and midbrain dopaminergic markers and showed functional activity comparable to standard 2D cultures.
When transplanted into the striatum of 6-OHDA-lesioned Parkinson's disease model mice, SAPNS microspheres significantly increased in vivo neuron survival compared with neurons transplanted in conventional suspension. Critically, the scaffold-transplanted neurons enabled significant motor function recovery using approximately an order of magnitude (roughly 10x) fewer neurons than have been previously required to demonstrate behavioral improvement.
Francis, Nicola L; Zhao, Nanxia; Calvelli, Hannah R; Saini, Astha; Gifford, Janace J; Wagner, George C; Cohen, Rick I; Pang, Zhiping P; Moghe, Prabhas V ·
RPEP-04808 · 2020The researchers designed 12-mer amphipathic helical peptides incorporating α,α-disubstituted amino acids (dAAs) to stabilize their secondary structure. Peptides with hydrophobic dAAs that adopted a helical conformation showed strong cell-penetrating ability.
One peptide containing dipropylglycine (a specific dAA) formed stable complexes with siRNA at appropriate size and surface charge for intracellular delivery. This peptide achieved effective RNA interference — meaning it successfully silenced target genes — in human hepatoma (liver cancer) cells at remarkably short peptide length and low concentrations of both the peptide and siRNA.
Furukawa, Kaori; Tanaka, Masakazu; Oba, Makoto ·
RPEP-04815 · 2020Backbone cyclization of α-conotoxin CIA produced analogues that retained low nanomolar potency at muscle-type nicotinic receptors while gaining up to 52-fold higher potency at the neuronal α3β2 subtype (IC50 1.3 nM). The cyclic analogues also showed greatly improved resistance to degradation in human serum. When tested in zebrafish, the peptides were highly paralytic both by injection (adults) and bath application (larvae), demonstrating barrier-crossing ability and efficient uptake — unusual properties for peptides of this size.
Giribaldi, Julien; Haufe, Yves; Evans, Edward R J; Amar, Muriel; Durner, Anna; Schmidt, Casey; Faucherre, Adèle; Moha Ou Maati, Hamid; Enjalbal, Christine; Molgó, Jordi; Servent, Denis; Wilson, David T; Daly, Norelle L; Nicke, Annette; Dutertre, Sébastien ·
RPEP-04819 · 2020The cell-penetrating peptide (CPP) was the key ingredient. Without CPP, the PLGA nanoparticles carrying plasmid DNA showed minimal cell uptake. With CPP attached, 84% of Beas-2B cells and 97% of A549 lung cancer cells internalized the nanoparticles within just 3 hours.
The particles entered cells mainly through clathrin-mediated endocytosis, a common cellular intake pathway. Once inside, the particles appeared to escape the endosome compartment, which is critical for the DNA cargo to reach its target. The delivered DNA produced green fluorescent protein (eGFP) in Beas-2B cells after 96 hours, confirming functional gene delivery.
The nanoparticles released about 50% of their DNA cargo in the first 24 hours, with encapsulation efficiency high enough to be practical.
Gomes Dos Reis, Larissa; Lee, Wing-Hin; Svolos, Maree; Moir, Lyn M; Jaber, Rima; Engel, Andrea; Windhab, Norbert; Young, Paul M; Traini, Daniela · In Vitro (Cell Culture)
RPEP-04821 · 2020In diabetic patients, Substance P (SP) and MCP-1 levels both rose significantly in the contralateral (opposite) eye after the first cataract surgery, whether the second surgery was 1 day or 1 week later (P ≤ 0.040). The SP increase in diabetic patients was significantly higher than in non-diabetic patients (P ≤ 0.030) at both time intervals.
MCP-1, a protein that attracts immune cells, also increased more in diabetic patients, reaching statistical significance in the 1-week interval group (P = 0.042).
This suggests that surgery on one eye triggers a sympathetic inflammatory response in the other eye, and diabetes amplifies this response. This may explain why diabetic patients often report more pain during their second eye surgery.
Gong, Xianhui; Ren, Yueping; Fang, Xiuxiu; Cai, Junyong; Song, E · Prospective Randomized Clinical Study
RPEP-04822 · 2020The review analyzes evidence on four FDA-approved anti-CGRP monoclonal antibodies: erenumab, fremanezumab, galcanezumab, and eptinezumab. All target either CGRP itself or its receptor in the trigeminovascular system.
The central question is whether these antibodies work inside the brain or outside it. At roughly 150 kDa (150,000 daltons), these molecules are far too large to cross an intact blood-brain barrier (BBB). Multiple studies confirm minimal BBB penetration.
The evidence points to peripheral mechanisms: the antibodies likely block CGRP signaling at sensory nerve endings in the meninges (brain coverings), at the trigeminal ganglion (a nerve cluster outside the BBB), and in peripheral blood vessels. Some researchers have suggested the antibodies might access areas where the BBB is leaky, such as the area postrema, but this remains debated.
González-Hernández, Abimael; Marichal-Cancino, Bruno A; García-Boll, Enrique; Villalón, Carlos M · Review
RPEP-04823 · 2020The review highlights three main applications of phage display in cancer immunotherapy. First, phage display identifies mimotopes, peptides that mimic the shape of cancer-specific antigens. These mimotopes can be used as vaccines to train the immune system to recognize real tumors.
Second, whole phage particles carrying cancer antigens on their surface act as natural vaccine platforms. The virus-like structure of phages triggers strong immune responses on its own, boosting the effect of the attached cancer antigens.
Third, phage display finds small peptides that directly activate immune cells, such as those that stimulate T cells or natural killer cells to attack tumors. Several preclinical studies show these approaches can shrink tumors in animal models.
Goracci, Martina; Pignochino, Ymera; Marchiò, Serena · Review
RPEP-04824 · 2020Both antimicrobial peptides showed clear antibacterial activity against three field strains of multi-drug resistant S. Enteritidis in standard lab tests. Minimum inhibitory concentrations (MIC) were 64 micromolar, and minimum bactericidal concentrations (MBC) were 128-256 micromolar, meaning the kill dose was 2-4 times the growth-stopping dose.
The peptides were stable across a range of conditions: high temperatures (70-90 degrees C), protease exposure (trypsin, proteinase K, lysozyme), varying salt concentrations, and pH range of 4.0 to 8.0. They did not damage red blood cells, showed minimal toxicity to RAW 264.7 macrophage and HEp-2 cells, and were safe for beneficial gut bacteria (L. acidophilus and L. rhamnosus).
The problem: once S. Enteritidis invaded immune cells (RAW 264.7 macrophages), neither peptide could kill it. They showed bacteriostatic (growth-stopping) effects in macrophages but no significant bactericidal (killing) effect in either cell line (P > 0.05).
Gourkhede, Diksha P; Bhoomika, Sirsant; Pathak, Richa; Yadav, Jay Prakash; Nishanth, Dani; Vergis, Jess; Malik, S V S; Barbuddhe, S B; Rawool, D B · In Vitro
RPEP-04825 · 2020The study performed a comprehensive bioinformatic search across all available mussel genomes and transcriptomes. The key finding is that mytilin-like peptides are more widespread and diverse than previously recognized.
All mytilins share a CS-alpha-beta structural scaffold, a common architecture found in defense peptides across nearly all branches of life. Despite low sequence similarity (the actual amino acid letters differ a lot), the backbone shape is conserved and stabilized by four disulfide bonds.
Variations in the alpha-helix size, beta-strand regions, and the positioning of one specific disulfide bond (C1-C5) suggest structural flexibility that could relate to different antimicrobial functions. The discovery of mytilins in Trichomya and Perna mussels extends the known range of these peptides beyond the previously studied Mytilus species.
Greco, Samuele; Gerdol, Marco; Edomi, Paolo; Pallavicini, Alberto · Bioinformatics/Computational
RPEP-04827 · 2020GLP-1 receptor agonist drugs reduce body weight by activating the same brain circuits that are naturally engaged by gut-derived GLP-1 after eating and by bariatric surgery.
Grill, Harvey J · Review
RPEP-04828 · 2020The researchers tested a set of modified di-peptides (doubled versions) derived from LF11, an 11-amino-acid fragment of human lactoferricin. They systematically varied length, positive charge, and hydrophobicity to find the optimal cancer-killing design.
The winners were R-DIM-P-LF11-215 and DIM-LF11-322, both with a net charge of +9 and moderate hydrophobicity. These showed the highest specific antitumor activity in standard 2D cultures and maintained their cancer-killing specificity in 3D multicellular tumor spheroids (MCTS).
One peptide, DIM-LF11-339, was highly hydrophobic and killed cancer cells in 2D but performed poorly in 3D. It could only kill cells at the outer edge of tumor spheroids, suggesting that too much hydrophobicity prevents peptides from penetrating into the center of solid tumors.
The peptides kill cancer cells by targeting phosphatidylserine, a lipid that sits on the outside of cancer cell membranes but stays hidden inside normal cell membranes. This is what gives the peptides their cancer specificity.
Grissenberger, Sarah; Riedl, Sabrina; Rinner, Beate; Leber, Regina; Zweytick, Dagmar · In Vitro
RPEP-04829 · 2020Of 27 bioactive peptides with chemical protection at both ends (to resist degradation), 13 remained stable after 72 hours at body temperature in horse plasma. The other 14 broke down to varying degrees.
The researchers identified specific breakdown products (catabolites) for all 14 unstable peptides, including novel catabolites never previously reported for chemotactic peptide, DALDA, dmtDALDA, deltorphins I and II, and several dermorphin analogs.
Key stability rules emerged: a D-amino acid (mirror image of normal) at position 2 or position 1 of a peptide, or next to its C-terminus, protected that end from degradation. But a D-amino acid at position 3 did not help. N-terminal modifications like pyroglutamic acid or N-methylation did not protect the N-terminal end. A C-terminal ethylamide group did protect against carboxypeptidase attack. The C-terminal lysine amide in DALDA, dmtDALDA, and Lys7-dermorphin was unexpectedly vulnerable to plasma enzymes.
Guan, Fuyu; Fay, Savannah; Li, Xiaoqing; You, Youwen; Robinson, Mary A · Analytical/Experimental
RPEP-04830 · 2020Vitamin D's protective effects in ulcerative colitis (UC) appear to work through cathelicidin, an antimicrobial peptide. In UC patients, higher vitamin D levels correlated with higher cathelicidin levels in both blood and colon tissue, and higher serum cathelicidin was associated with decreased risk of histologic inflammation and clinical relapse. In lab experiments, vitamin D treatment of human colon cells induced cathelicidin production and the anti-inflammatory cytokine IL-10, suppressed the pro-inflammatory cytokine TNF-α, and killed E. coli bacteria — an antimicrobial effect that disappeared when cathelicidin was knocked down. In mice, rectal cathelicidin administration reduced the severity of chemically induced colitis.
Gubatan, John; Mehigan, Gillian A; Villegas, Fernando; Mitsuhashi, Shuji; Longhi, Maria Serena; Malvar, Grace; Csizmadia, Eva; Robson, Simon; Moss, Alan C · Human And Animal
RPEP-04831 · 2020The review connects three bodies of evidence. First, epidemiological data shows vitamin D deficiency is associated with higher risk of streptococcal infections, including pneumonia, meningitis, sepsis, and skin infections.
Second, vitamin D directly stimulates production of antimicrobial peptides, particularly cathelicidin (LL-37) and lactoferrin. These peptides punch holes in bacterial membranes and modulate immune cell behavior.
Third, vitamin D enhances other innate immune functions: phagocytosis (immune cells physically engulfing bacteria) and oxidative burst (production of reactive oxygen species that kill engulfed bacteria). Together, these mechanisms explain why low vitamin D leaves people more vulnerable to streptococcal infections.
Guevara, Miriam A; Lu, Jacky; Moore, Rebecca E; Chambers, Schuyler A; Eastman, Alison J; Francis, Jamisha D; Noble, Kristen N; Doster, Ryan S; Osteen, Kevin G; Damo, Steven M; Manning, Shannon D; Aronoff, David M; Halasa, Natasha B; Townsend, Steven D; Gaddy, Jennifer A · Review
RPEP-04832 · 2020The researchers cloned rabbit NLRX1 (rNLRX1) for the first time and found it contains a NACHT domain and seven leucine-rich repeats. It was expressed widely across rabbit tissues and increased sharply in liver, spleen, kidney, and colon after EHEC infection.
Overexpressing rNLRX1 suppressed NF-kB signaling, the master switch for inflammation. This reduced production of pro-inflammatory cytokines (IL-1beta, TNF-alpha) and beta-defensins (DEFB114, DEFB124, DEFB125). The result: bacteria grew faster.
Knocking down rNLRX1 had the opposite effect. NF-kB activation increased, cytokines and defensins rose, and EHEC growth was inhibited. This identifies NLRX1 as a negative regulator of antimicrobial defense, essentially a brake pedal on the immune response.
Guo, Mengjiao; Zhang, Congyue; Zhang, Chengcheng; Zhang, Xiaorong; Wu, Yantao · In Vitro