RPEP-08041 · 2024The review identified multiple peptides demonstrating efficacy in soft tissue repair across oral and intra-articular delivery routes. Intra-articular (joint injection) peptides provided localized therapeutic effects directly at the injury site, while oral peptides offered systemic benefits that could support broader tissue healing.
Both routes showed distinct advantages: joint injections bypass digestive breakdown but are more invasive and require clinical visits, while oral peptides are convenient but face significant bioavailability and absorption challenges in the gut. The field remains in its early stages, with most evidence coming from preclinical studies and limited human trials. The review positions peptide treatments as promising pre-surgical alternatives for soft tissue regeneration.
Cushman, Caroline J; Ibrahim, Andrew F; Smith, Alexander D; Hernandez, Evan J; MacKay, Brendan; Zumwalt, Mimi ·
RPEP-08044 · 2024Cagrilintide is a long-acting analog of amylin, which reduces appetite through both homeostatic (hunger-regulating) and hedonic (pleasure/reward) brain pathways. Combined with semaglutide (a GLP-1 receptor agonist that reduces appetite via hypothalamic GLP-1 receptors, increases insulin, reduces glucagon, and delays gastric emptying), the two peptides have separate but complementary mechanisms that produce additive appetite reduction.
Clinical trials have demonstrated promising weight loss with both cagrilintide alone and the cagrilintide-semaglutide combination, supporting further development of this dual-peptide approach for sustained weight management.
D'Ascanio, Antonella M; Mullally, Jamie A; Frishman, William H ·
RPEP-08045 · 2024This perspective article argues that while mono, dual, and triple agonists of GLP-1, GIP, and glucagon receptors produce impressive weight loss, fundamental biological principles about hunger and satiety raise important questions that go beyond currently reported side effects. The authors contend that suppressing hunger through pharmacology does not bypass the complex goal-oriented behaviors, systemic metabolism, and cellular metabolic processes that govern how the body regulates energy balance. They caution against treating these drugs as a simple silver bullet for obesity without understanding the deeper biological implications of overriding the hunger-satiety system.
D'Ávila, Mateus; Hall, Samantha; Horvath, Tamas L · Perspective
RPEP-08059 · 2024High hydrostatic pressure (HHP) at 300 MPa combined with Alcalase enzyme digestion produced the most potent quinoa protein hydrolysates. These showed the highest ACE-inhibitory activity (anti-hypertensive potential), enhanced antioxidant activity, and 1.8-fold increase in total flavonoids compared to non-hydrolyzed quinoa protein isolate. Three specific peptide sequences — GSHWPFGGK, FSIAWPR, and PWLNFK — had the highest Peptide Ranker scores and were predicted to have ACE-inhibitory, DPP-IV inhibitory, and antioxidant activities. Pressure at 300-400 MPa caused more extensive protein breakdown than enzyme alone.
de Carvalho Oliveira, Ludmilla; Martinez-Villaluenga, Cristina; Frias, Juana; Elena Cartea, María; Francisco, Marta; Cristianini, Marcelo; Peñas, Elena ·
RPEP-08060 · 2024Semaglutide was not associated with increased risk of any of 22 neurological or psychiatric outcomes over 12 months compared to three other diabetes medications. Instead, it was associated with significantly reduced risk of cognitive deficit (HR 0.72, 95% CI 0.64–0.80 vs sitagliptin; HR 0.72, 95% CI 0.63–0.81 vs glipizide), dementia (HR 0.52, 95% CI 0.40–0.68 vs sitagliptin), and nicotine misuse (HR 0.72, 95% CI 0.61–0.85 vs glipizide; HR 0.77, 95% CI 0.65–0.90 vs empagliflozin). No differences were observed in negative control outcomes, strengthening confidence in the findings.
De Giorgi, Riccardo; Koychev, Ivan; Adler, Amanda I; Cowen, Philip J; Harmer, Catherine J; Harrison, Paul J; Taquet, Maxime ·
RPEP-08066 · 2024Among 4,286 patients with heart failure at enrollment (out of 17,604 total), semaglutide 2.4 mg weekly significantly improved all cardiovascular outcomes compared to placebo: MACE HR 0.72 (95% CI 0.60–0.87), composite heart failure endpoint HR 0.79 (0.64–0.98), cardiovascular death HR 0.76 (0.59–0.97), and all-cause death HR 0.81 (0.66–1.00).
Benefits were consistent across heart failure subtypes: HFrEF showed MACE HR 0.65 (0.49–0.87) and HFpEF showed MACE HR 0.69 (0.51–0.91). No significant treatment interaction was observed across age, sex, BMI, NYHA status, or diuretic use subgroups. Serious adverse events were less frequent with semaglutide regardless of heart failure subtype.
Deanfield, John; Verma, Subodh; Scirica, Benjamin M; Kahn, Steven E; Emerson, Scott S; Ryan, Donna; Lingvay, Ildiko; Colhoun, Helen M; Plutzky, Jorge; Kosiborod, Mikhail N; Hovingh, G Kees; Hardt-Lindberg, Søren; Frenkel, Ofir; Weeke, Peter E; Rasmussen, Søren; Goudev, Assen; Lang, Chim C; Urina-Triana, Miguel; Pietilä, Mikko; Lincoff, A Michael ·
RPEP-08068 · 2024The primary endpoint — change in ADAS-Cog11 cognitive score at 32 weeks — showed no significant difference between exenatide and control groups (p=0.17). A gender interaction was detected (p=0.04), driven by worsening ADAS-Cog11 scores in women randomized to exenatide (p=0.018), even after adjusting for age, education level, dysglycemia, and baseline cognitive scores.
Exenatide did demonstrate expected metabolic effects: fasting plasma glucose decreased (p=0.02) and body weight decreased (p=0.03) in the treatment group, confirming GLP-1 receptor engagement. However, these metabolic improvements did not translate into cognitive benefits.
Dei Cas, A; Micheli, M M; Aldigeri, R; Gardini, S; Ferrari-Pellegrini, F; Perini, M; Messa, G; Antonini, M; Spigoni, V; Cinquegrani, G; Vazzana, A; Moretti, V; Caffarra, P; Bonadonna, R C ·
RPEP-08069 · 2024After 52 weeks, patients on liraglutide maintained their C-peptide response (a measure of natural insulin production) while placebo patients saw theirs decline significantly (P = .002). The liraglutide group needed less insulin over time — dropping from 0.30 to 0.23 units/kg/day — while the placebo group's needs increased from 0.29 to 0.43 units/kg/day (P < .001).
Thirteen liraglutide patients achieved periods without any insulin injections, lasting an average of 22 weeks (range: 3–52 weeks), compared to only two placebo patients who managed an average of 6 weeks insulin-free. However, six weeks after stopping liraglutide, C-peptide levels were similar between groups, indicating the benefit did not persist after discontinuation.
Dejgaard, Thomas F; Frandsen, Christian S; Kielgast, Urd; Størling, Joachim; Overgaard, Anne J; Svane, Maria S; Olsen, Markus Harboe; Thorsteinsson, Birger; Andersen, Henrik U; Krarup, Thure; Holst, Jens J; Madsbad, Sten ·
RPEP-08070 · 2024In 30 severely obese non-diabetic adults (15 exenatide, 15 diet-only control) over 3 months:
Fasting improvements with exenatide:
- Reduced ceramides (CERs) and lysophosphatidylcholines (LPCs) linked to cardiometabolic risk
- Relatively increased unsaturated phospholipid species (PC, LPC) with protective cardiovascular effects
- Total lipid species concentrations unchanged — the composition shifted beneficially
Postprandial improvements:
- Significantly lowered postprandial triglycerol (TAG) concentrations, particularly saturated TAGs with 44-54 carbons
- Reduced free fatty acid clearance
- Reduced postprandial ceramides and lipid species linked to cardiometabolic risk
All changes remained statistically significant after adjusting for weight loss (-5.5% vs -1.9%, P = 0.052), demonstrating weight loss-independent effects.
Della Pepa, Giuseppe; Patrício, Bárbara G; Carli, Fabrizia; Sabatini, Silvia; Astiarraga, Brenno; Ferrannini, Ele; Camastra, Stefania; Gastaldelli, Amalia ·
RPEP-08076 · 2024A novel 'high-functional' bovine collagen peptide (Type J) significantly improved knee osteoarthritis symptoms at all tested doses (2.5g, 5g, and 10g daily) over 90 days. The most striking finding was that just 2.5g of the Type J collagen peptide performed equivalently to 10g of conventional collagen peptides across multiple outcome measures including pain, joint function, quality of life, cartilage degradation biomarkers (CTX-II), and MRI-based structural assessment (MOAKS).
All collagen peptide groups — both Type J and conventional — outperformed placebo, confirming that collagen peptide supplementation provides real benefit for knee osteoarthritis beyond placebo effect.
Devasia, Sheena; Joseph, Jinu T; P S, Stephena; Koizumi, Seiko; Clarke, Liz; V T, Sriraam; Kailas, Abhilash Parameswaran; Madhavan, Shajil · Randomized Controlled Trial
RPEP-08086 · 2024Skin mucus from three fish species showed antiviral activity against herpes simplex virus type 1 (HSV-1), with sea bream and rainbow trout mucus demonstrating higher activity (2-4 and 2-5 inhibition, respectively) than sea bass (2-2). The higher antiviral activity correlated with higher levels of antimicrobial peptides — cathelicidin, hepcidin, galectin 2, and C10ORF99 — in the mucus of the more effective species.
The association between AMP levels and antiviral potency suggests these peptides contribute directly to the antiviral defense of fish skin mucus, pointing to their potential as novel antiviral agents or supplements.
Dik, Irmak; Dik, Burak; Tufan, Öznur; Er, Ayşe ·
RPEP-08088 · 2024Across more than 30 clinical trials involving over 11,000 human subjects worldwide, thymosin alpha-1 demonstrated consistent safety and efficacy as an immune modulator. The peptide showed significant effectiveness in treating COVID-19 (improving immune function in severe cases), autoimmune conditions (restoring immune balance), and cancer (enhancing immune-mediated anti-tumor responses). No patterns of serious safety concerns emerged across the reviewed trials. The authors conclude the FDA's 2023 restriction on compounding pharmacies producing Tα1 is not supported by the clinical evidence base.
Dinetz, Elliot; Lee, Edwin ·
RPEP-08089 · 2024The Pc-AT-CLs (protein corona-AT 1002-cationic liposomes) system demonstrated a two-stage adaptive delivery mechanism for oral liraglutide:
- Stage 1 (mucus penetration): BSA protein corona provided a hydrophilic, electrically neutral surface that reduced mucus adherence. Mucus penetration was 1.45 times greater than uncoated AT-CLs.
- Stage 2 (epithelial transport): After penetrating the mucus layer, the protein corona fell off, exposing the AT 1002 peptide and cationic surface. The apparent permeability coefficient (Papp) of AT-CLs was 2.03 times that of unmodified cationic liposomes.
In vivo testing showed significant hypoglycemic (blood sugar-lowering) effects and enhanced relative bioavailability compared to free liraglutide, confirming that the system protected liraglutide from degradation and improved its oral absorption.
Ding, Ruihuan; Li, Yanping; Zheng, Wei; Sun, Yiying; Zhao, Zhenyu; Zhang, Houqian; Yuan, Ranran; Wang, Aiping; Sun, Kaoxiang; Wang, Hongbo; Shi, Yanan ·
RPEP-08090 · 2024A single aza-amino acid substitution (carbon → nitrogen) at the second position from the N-terminus made GLP-1 and GIP peptide agonists completely resistant to DPP4 degradation while retaining full potency and efficacy at their respective receptors (GLP-1R and GIPR).
Molecular dynamics simulations confirmed that aza-amino acids can adopt the same conformational space as natural amino acids when the peptide binds its receptor. The modification was successfully applied to semaglutide and a dual GLP-1R/GIPR agonist, demonstrating it works as a viable alternative to existing DPP4 resistance strategies and offers additional structural variation that may influence downstream signaling.
Dinsmore, Tristan C; Liu, Jamie; Miao, Jiayuan; Ünsal, Özge; Sürmeli, Damla; Beinborn, Martin; Lin, Yu-Shan; Kumar, Krishna ·
RPEP-08093 · 2024Using 2023 national retail prices for GLP-1 receptor agonists compared to inflation-adjusted 2015 surgical costs, the cumulative medication costs surpassed surgery costs relatively quickly:
- Saxenda and Wegovy exceeded the cost of sleeve gastrectomy within approximately 9 months
- Saxenda and Wegovy exceeded the cost of Roux-en-Y gastric bypass in less than 1 year
- Byetta (the most affordable GLP-1 RA) became costlier than either surgery after approximately 1.5 years
GLP-1 drugs also take time to reach full effectiveness, delaying weight loss while costs accumulate, and weight typically returns after discontinuation.
Docimo, Salvatore; Shah, Jay; Warren, Gus; Ganam, Samer; Sujka, Joseph; DuCoin, Christopher ·
RPEP-08096 · 2024Researchers created the LUSBI protocol — combining lung ultrasound, BREST heart failure risk scores, and inferior vena cava measurements — to distinguish cardiac from non-cardiac causes of shortness of breath in the emergency department. The protocol was validated against NT-proBNP, a peptide biomarker for heart failure.
NT-proBNP values differed significantly across LUSBI protocol profiles (p=0.004), confirming that the protocol's ultrasound-based classifications align with biochemical evidence of heart failure. There was also a significant difference (p=0.001) in LUSBI profiles between patients categorized by central venous pressure.
The protocol proved effective for quickly confirming or ruling out a cardiac cause of breathing difficulty in 80 emergency department patients.
Dojcinovic, Boris; Banjac, Nada; Vukmirovic, Sasa; Dojcinovic, Tamara; Vasovic, Lucija V; Mihajlovic, Dalibor; Vasovic, Velibor · Clinical Study
RPEP-08097 · 2024Over a median follow-up of 383 days, 74 heart transplant recipients on GLP-1 receptor agonists showed significant improvements: mean BMI decreased from 33.3 to 31.5 kg/m² (p < 0.0001), HbA1c from 7.3% to 6.7% (p = 0.005), LDL cholesterol from 78.6 to 70.3 mg/dL (p = 0.018), and basal insulin daily dose from 32.6 to 24.8 units (p = 0.0002).
The majority (76%) received semaglutide. Primary indications were T2DM alone (45%) or combined T2DM and obesity (35%). The drugs were well tolerated and rarely required adjustments to immunosuppression dosing — a critical safety consideration in transplant patients.
Donald, Elena M; Driggin, Elissa; Choe, Jason; Batra, Jaya; Vargas, Fabian; Lindekens, Jordan; Fried, Justin A; Raikhelkar, Jayant K; Bae, David J; Oh, Kyung T; Yuzefpolskaya, Melana; Colombo, Paolo C; Latif, Farhana; Sayer, Gabriel; Uriel, Nir; Clerkin, Kevin J; DeFilippis, Ersilia M ·
RPEP-08098 · 2024Pulpitis induced significant increases in CGRP-positive neurons and GFAP-positive satellite glial cells (SGCs) in the trigeminal ganglia, along with massive mast cell degranulation. Degranulated mast cells were scattered among CGRP-positive nerve fibers and tryptase-positive mast cells surrounded neurons.
Curcumin treatment: significantly decreased TNF-α, reduced mast cell degranulation, downregulated CGRP expression, decreased TLR4-positive neurons, reduced activated SGCs, lowered PAR2-positive neurons, decreased tryptase expression, and attenuated osteoclast activation in the apical periodontium. This demonstrates that curcumin can suppress the mast cell-CGRP neuroimmune axis in dental inflammation.
Dong, Ming; Tang, Jing; Li, Lu-Jia; Dai, Ting; Zuo, Yi-Yan; Jin, Hai-Wei ·
RPEP-08099 · 2024The two novel peptides, E(FKFE)2 and K(FEFK)2, formed transparent hydrogels at pH 7 through physical self-assembly without chemical cross-linking. The charge state of the peptides directly controlled whether samples formed solutions, gels, or precipitates.
When loaded with oppositely charged polymers, the hydrogel network changed fundamentally: individual fibrils became smaller, but fiber bundling and aggregation increased, creating denser cross-links. This translated to stiffer, more stable gels that resisted swelling in excess media. Polymer diffusion out of the gel was controlled by electrostatic interactions — oppositely charged polymers diffused more slowly, enabling tunable sustained release. The gels supported 3D culture of 3T3 fibroblasts and human mesenchymal stem cells.
Dong, Siyuan; Chapman, Sam L; Pluen, Alain; Richardson, Stephen M; Miller, Aline F; Saiani, Alberto ·
RPEP-08107 · 2024The review highlights that tirzepatide exhibits a biased signaling profile at the GLP-1 receptor, characterized by preferential Gαs activation over β-arrestin recruitment. This biased signaling appears to contribute to tirzepatide's superior insulinotropic and weight-reducing effects compared to balanced GLP-1R agonists in preclinical models.
This represents a significant finding because it demonstrates that subtle differences in how a drug interacts with the same receptor can produce clinically meaningful differences in efficacy — moving biased agonism from a theoretical concept to a practical design principle for drug development. The review also catalogues other biased GLP-1R agonists in industry pipelines and their structural determinants.
Douros, Jonathan D; Mokrosinski, Jacek; Finan, Brian ·
RPEP-08110 · 2024In rats receiving cisplatin chemotherapy for 5 weeks:
Exenatide-treated group (Group 2) vs cisplatin-only group (Group 1):
- Significantly higher numbers of primordial, primary, secondary, and tertiary follicles
- Significantly lower ovarian fibrosis percentage
- Higher plasma anti-Mullerian hormone (indicating better preserved ovarian reserve)
- Lower NLRP3 inflammasome levels (reduced inflammation)
- Lower TLR4 levels (reduced innate immune activation)
- Lower Nrf-2 levels (indicating less oxidative stress burden)
Exenatide-treated rats had ovarian parameters closer to the healthy control group (Group 0), demonstrating meaningful protection.
Doğan, Gül O; Erbaş, Oytun ·
RPEP-08112 · 2024After 3 months of varenicline-assisted smoking cessation in patients with T2DM/prediabetes, the 32 successful quitters showed no significant weight gain, no worsening of glycemic control, and significant improvements in lipid profile (total cholesterol 168→156 mg/dL, p=0.013; LDL 96→83 mg/dL, p=0.013). GLP-1 levels rose significantly (39.6→45.8 pM, p=0.016) and leptin increased (11→13.8 ng/dL, p=0.004). Physical activity also increased, with moderate-intensity activity participation rising from 28% to 56% (p=0.039).
Driva, Stamatina; Korkontzelou, Aliki; Tonstad, Serena; Tentolouris, Nikolaos; Litsiou, Eleni; Vasileiou, Vasiliki; Vassiliou, Alice G; Saltagianni, Vassiliki; Katsaounou, Paraskevi ·
RPEP-08113 · 2024In normal mice, oxytocin (OXT) and vasopressin (AVP) from the supraoptic nucleus promote inhibitory transmission in the lateral septum, keeping somatostatin (SST) neurons suppressed. In the Magel2 knockout mouse model of PWS, this neuropeptide signaling fails, causing SST neurons to become disinhibited. This disrupts social-fear extinction and triggers aggressive behavior.
The deficit mapped specifically to the supraoptic nucleus → lateral septum pathway. Optogenetic or pharmacological inhibition of SST neurons in the LS corrected social-fear extinction deficits and suppressed aggression outbursts, demonstrating a direct causal link and a potential therapeutic target.
Dromard, Yann; Borie, Amélie M; Chakraborty, Prabahan; Muscatelli, Françoise; Guillon, Gilles; Desarménien, Michel G; Jeanneteau, Freddy ·
RPEP-08114 · 2024The review establishes that GLP-1RA have proven cardiorenal benefits beyond glucose and weight control in select populations. Key safety topics addressed include:
- **Muscle and bone**: GLP-1 drugs cause some muscle loss alongside fat loss, with emerging data on bone density and fracture risk
- **GI motility**: Slowed gastric emptying raises concerns about retained stomach contents before anesthesia
- **Pancreas and biliary tract**: Ongoing monitoring for pancreatitis and gallbladder disorders
- **Cancer risk**: Current evidence assessed across multiple cancer types
- **Exercise capacity**: How weight loss affects physical performance
Next-generation molecules discussed include tirzepatide (GIP-GLP-1 coagonist), maritide (GIP blocker + GLP-1 activator), retatrutide and survodutide (glucagon + GLP-1 activators), each with distinct pharmacological profiles.
Drucker, Daniel J ·
RPEP-08116 · 2024After 12 weeks of liraglutide monotherapy (0.6-1.8 mg/day) in 71 obese subjects:
- Significant weight loss (p<0.001)
- Fasting blood glucose, 2-hour post-load glucose, and HbA1c all significantly improved (all p<0.001)
- Subcutaneous adipose tissue (SAT): significantly reduced (p<0.001)
- Visceral adipose tissue (VAT): significantly reduced (p<0.001)
- Liver fat content (LFC): significantly reduced (p<0.001)
Subgroup analysis:
- Patients with impaired glucose regulation (IGR) had higher baseline liver fat than those with normal glucose tolerance (NGT) (p=0.002)
- IGR patients showed significantly greater liver fat reduction than NGT patients (p<0.001)
- Liver fat reduction correlated with fasting glucose improvement (r=0.587, p<0.001) and HbA1c improvement (r=0.607, p<0.001)
Du, Mengyang; Yue, Jiang; Qi, Yicheng; He, Shengyun; Lu, Xiaobing; Yang, Minglan; Wang, Lihua; Lu, Qing; Ma, Jing ·
RPEP-08122 · 2024In 45 patients with grade 1-2 neuroendocrine tumors, [18F]FET-βAG-TOCA PET/CT was noninferior to [68Ga]Ga-DOTA-peptide PET/CT. Both tracers detected 285 lesions with excellent SUVmax correlation (r = 0.91). The fluorine-18 tracer detected 13 additional tumor deposits in 8 patients that the gallium-68 scan missed, while the gallium-68 tracer found 7 additional lesions in 5 patients. The only significant difference was in liver metastases, where the gallium-68 tracer showed better tumor-to-background ratios (3.5 vs. 2.5, p<0.05).
Dubash, Suraiya; Barwick, Tara D; Kozlowski, Kasia; Rockall, Andrea G; Khan, Sairah; Khan, Sameer; Yusuf, Siraj; Lamarca, Angela; Valle, Juan W; Hubner, Richard A; McNamara, Mairéad G; Frilling, Andrea; Tan, Tricia; Wernig, Florian; Todd, Jeannie; Meeran, Karim; Pratap, Bhavesh; Azeem, Saleem; Huiban, Michael; Keat, Nicholas; Lozano-Kuehne, Jingky P; Aboagye, Eric O; Sharma, Rohini ·
RPEP-08129 · 2024Key results from 3 RCTs with 430 participants:
**CagriSema vs semaglutide 2.4 mg (20-32 weeks):**
- Extra percentage weight loss: -9.07% (95% CI: -11.91 to -6.23)
- Extra absolute weight loss: -9.11 kg (95% CI: -12.84 to -5.39)
- GI adverse events and vomiting were significantly higher with CagriSema
**Cagrilintide 2.4 mg vs semaglutide/liraglutide (26-32 weeks):**
- Percentage weight loss: similar (MD -1.83%, non-significant, p=0.11)
- Absolute weight loss: similar (MD -1.88 kg, non-significant, p=0.12)
- Vomiting was significantly lower with cagrilintide
Treatment-emergent and serious adverse events were comparable across all groups.
Dutta, Deep; Nagendra, Lakshmi; Harish, B G; Sharma, Meha; Joshi, Ameya; Hathur, Basavanagowdappa; Kamrul-Hasan, Abm ·
RPEP-08131 · 2024Across 8 studies and 557 individuals, liraglutide produced significantly greater weight loss than placebo after 6 months: -6.0 kg (95% CI: -8.66 to -3.33; p<0.001). Semaglutide outperformed liraglutide at both 6 months (-2.57% body weight difference; 95% CI: -3.91 to -1.23) and 12 months (-4.15% body weight difference; 95% CI: -6.96 to -1.34; p=0.004).
Semaglutide users were significantly more likely to achieve >15% weight loss (OR 2.15; p=0.03) and >10% weight loss (OR 2.10; p=0.01) at 12 months compared to liraglutide. Liraglutide significantly reduced fat mass (-4.78 kg). However, the authors noted that bone health deterioration and muscle mass loss remain concerns requiring further evaluation.
Dutta, Deep; Nagendra, Lakshmi; Joshi, Ameya; Krishnasamy, Suryashri; Sharma, Meha; Parajuli, Naresh ·
RPEP-08133 · 2024The review identifies cathelicidins' therapeutic potential across multiple skin conditions:
- **Infections**: Broad-spectrum activity against bacteria, viruses, and fungi, including antibiotic-resistant strains
- **Wound healing**: LL-37 promotes wound closure and skin barrier restoration, particularly relevant for diabetic foot ulcers
- **Cancer**: Some cathelicidins show anti-melanoma activity
- **Acne**: Antimicrobial and anti-inflammatory effects relevant to acne pathology
However, significant translational barriers exist: many peptide therapies have failed clinical trials due to unclear efficacy and safety; bacterial resistance to cathelicidins has emerged (contradicting initial claims); large-scale production is costly; drug stability and delivery formulation remain challenging.
Dzurová, Lenka; Holásková, Edita; Pospíšilová, Hana; Schneider Rauber, Gabriela; Frébortová, Jitka ·
RPEP-08139 · 2024Semaglutide produced a statistically significant reduction in abdominal visceral adipose tissue of 30.82 cm² (95% CI: -50.13 to -11.51), representing a 30.6% decrease compared to placebo over 32 weeks. Abdominal subcutaneous fat also decreased by 42.01 cm² (11.2% reduction), and total body fat dropped by 18.9%.
These reductions occurred without a statistically significant increase in treatment-related adverse events, though one grade 4 elevated lipase event and two cases of cholelithiasis were observed in the semaglutide group.
Eckard, Allison Ross; Wu, Qian; Sattar, Abdus; Ansari-Gilani, Kianoush; Labbato, Danielle; Foster, Theresa; Fletcher, Aaron A; Adekunle, Ruth O; McComsey, Grace A ·
RPEP-08140 · 2024The GLP-1 receptor agonist exendin-4 (Ex4) reduced levels of taurine, glycine, and serine in the nucleus accumbens — the brain's reward center — of male rats. The decreases in taurine and glycine appeared to involve GLP-1 receptor activation in the nucleus tractus solitarius (NTS), a brainstem region that relays gut signals to the brain.
Systemic Ex4 injection also elevated metabolites of dopamine (DOPAC and HVA) and serotonin (5HIAA) in the nucleus accumbens. The dopamine-related metabolite increases involved GLP-1 receptors outside the NTS, suggesting multiple brain pathways are involved in how GLP-1 drugs modulate reward-related behavior.
Edvardsson, Christian E; Vestlund, Jesper; Ericson, Mia; Jerlhag, Elisabet · Animal Study
RPEP-08144 · 2024Melittin, the primary peptide in bee venom, was enzymatically hydrolyzed into smaller bioactive peptide fragments that showed superior anticancer selectivity compared to intact melittin. All tested peptides displayed antibacterial, anti-biofilm, and anticancer activities against both Gram-positive and Gram-negative bacteria and two cancer cell lines (Huh-7 liver cancer and HCT 116 colon cancer). Crucially, neither melittin nor its fragments affected the viability of normal human lung cells (Wi-38), and the hydrolyzed fractions had better selectivity indices (greater cancer cell killing relative to normal cell toxicity) than whole melittin.
El-Didamony, Samia E; Kalaba, Mohamed H; Sharaf, Mohamed H; El-Fakharany, Esmail M; Osman, Ali; Sitohy, Mahmoud; Sitohy, Basel ·
RPEP-08145 · 2024Psoriasis patients had significantly higher tissue levels of substance P compared to healthy controls. Excimer light therapy (9 sessions) reduced both substance P and its receptor (NK-1R) levels in psoriatic skin, along with significant clinical improvements in disease severity (PSI) and itching (VAS). The treatment was effective for both active and stable plaque psoriasis, with no significant difference between groups. This suggests excimer light works partly by dampening neurogenic inflammation mediated by substance P.
El-Mesidy, Marwa S; Metwally, Yomna A; Nour, Zeinab A; Elmasry, Maha F ·
RPEP-08148 · 2024Over 28 days, GEP44 (a GLP-1R/Y1R/Y2R triple agonist) produced body weight reductions of -15.6% in males and -11.9% in females versus vehicle, compared to -9.7% (males) and -5.1% (females) with liraglutide. Cumulative food intake reductions were also significantly greater: GEP44 reduced intake by -39% in males and -30% in females versus -20% and -10% with liraglutide, respectively.
Glucose tolerance tests showed similar stimulation of glucose-induced insulin secretion between GEP44 and liraglutide, indicating comparable glycemic effects despite the superior weight loss with the triple agonist.
Elfers, Clinton T; Chichura, Kylie S; Ashlaw, Emily F; Chepurny, Oleg G; Holz, George G; Doyle, Robert P; Roth, Christian L ·
RPEP-08150 · 2024Out of 3,415 patients who underwent upper endoscopy over eight years, 129 (3.8%) had clinically significant delayed gastric emptying (CSDGE) with retained stomach contents.
GLP-1 receptor agonist use was associated with only 2% of CSDGE cases — the lowest frequency among all assessed factors. Opioid use accounted for 35% of cases, the highest contribution.
The odds ratio for CSDGE in GLP-1 RA users was 2.5, but the confidence interval was wide (95% CI: 0.75-8.29) and crossed 1.0, meaning the association was not statistically significant. Critically, every patient who had CSDGE while on a GLP-1 RA was simultaneously taking other medications or had conditions independently associated with delayed gastric emptying.
Elimihele, Thomas A; Mangrola, Anjali M; Oshomoji, Oluwatobi; Wilson, Nateshia B; Nnamani, Ikenna; Ashong, Bryan; Billings, Sunteasja; Getu, Daniel K; Kumar, Sachin; Maliakkal, Benedict ·
RPEP-08163 · 2024This review maps the full landscape of glucagon-based obesity therapies, from single-receptor agonists to the newest triple-agonist drugs. Glucagon — traditionally seen as a blood-sugar-raising hormone — is being reframed as a metabolic multitool that boosts energy expenditure, suppresses appetite, and promotes fat burning.
The review covers single glucagon receptor agonists, dual agonists (GLP-1/glucagon like survodutide, and GLP-1/GIP like tirzepatide), and the emerging triple agonists that target GLP-1, GIP, and glucagon receptors simultaneously (like retatrutide). It also discusses combination approaches involving amylin, thyroid hormone (T3), FGF21, and peptide YY. Triple agonists show the most potent weight loss in early trials, leveraging the additive metabolic benefits of activating all three receptor pathways.
Enyew Belay, Kibret; Jemal, Rebil Heiru; Tuyizere, Aloys · Review
RPEP-08164 · 2024Adding three arginine amino acids to the outside of a cyclic melanocortin peptide made it more effective at suppressing food intake in mice, both when injected into the spinal canal (intrathecally) and under the skin (subcutaneously). The modified peptide maintained or increased potency at melanocortin receptors in cell-based assays, and the in vivo appetite suppression exceeded what lab tests predicted.
This arginine-addition strategy was inspired by setmelanotide, an FDA-approved melanocortin drug for genetic obesity that also uses an extracyclic arginine critical for its activity.
Ericson, Mark D; Freeman, Katie T; Larson, Courtney M; Bouchard, Jacob L; John, Kristen; Lunzer, Mary M; Koerperich, Zoe M; Haskell-Luevano, Carrie · Preclinical
RPEP-08166 · 2024A patient using fremanezumab (a CGRP-blocking antibody for migraine prevention) developed persistent hair loss localized to the injection site on the lower extremity. This is notable because most reported CGRP inhibitor-related alopecia has been scalp-based and associated with erenumab, not fremanezumab.
The proposed mechanism is that blocking CGRP removes its immunomodulatory protection of hair follicles, causing the follicle's 'immune privilege' to collapse — essentially, the immune system attacks hair follicles that were previously shielded by CGRP signaling.
Esguerra, Mark; Engel, Emily Rubenstein · Case Report
RPEP-08168 · 2024Despite a black box warning based on rodent studies showing a link between GLP-1 receptor agonists and medullary thyroid cancer (MTC), this narrative review finds no conclusive evidence of elevated thyroid cancer risk in humans. Randomized controlled trials show thyroid cancer is rare in GLP-1 RA users, with imprecise effect estimates that do not consistently demonstrate increased risk. Observational studies yield inconsistent results. While pharmacovigilance databases show increased thyroid cancer reporting, these studies cannot establish causation. The biological plausibility for MTC in rodents does not clearly extend to non-MTC thyroid cancer in humans.
Espinosa De Ycaza, Ana E; Brito, Juan P; McCoy, Rozalina G; Shao, Hui; Singh Ospina, Naykky ·
RPEP-08172 · 2024This review maps how thymosin β4 and thymosin β10 are expressed across human organs throughout development — from fetal stages through different ages after birth. The research group used proteomics (on preterm newborn saliva and gingival fluid) and immunohistochemistry (on autopsy tissues from fetuses and adults) to track these two peptides over time and across tissues.
Key discoveries include that β-thymosins are expressed in organ-specific and age-dependent patterns, with important implications for understanding their roles in development and disease. The review addresses the 'β-thymosin enigma' — the puzzle of how these small, seemingly simple peptides can have such diverse biological functions across so many tissues, including roles in carcinogenesis.
Faa, Gavino; Messana, Irene; Coni, Pierpaolo; Piras, Monica; Pichiri, Giuseppina; Piludu, Marco; Iavarone, Federica; Desiderio, Claudia; Vento, Giovanni; Tirone, Chiara; Manconi, Barbara; Olianas, Alessandra; Contini, Cristina; Cabras, Tiziana; Castagnola, Massimo · Review
RPEP-08174 · 2024The COA-T3 hydrogel, composed of quaternized chitosan and oxidized dextran, successfully co-delivered the antimicrobial peptide HHC10 and the photosensitizer TPI-PN via pH-sensitive release. In vitro, the hydrogel showed remarkable activity against drug-resistant bacteria. In vivo, it significantly promoted healing of infected diabetic wounds in mice.
The dual mechanism — antimicrobial peptide killing combined with photodynamic therapy — provided enhanced antibacterial activity compared to either approach alone. The pH-responsive release ensured both agents were delivered specifically at the infected wound site. The hydrogel also demonstrated excellent biocompatibility, supporting its potential as a wound dressing material.
Fan, Duoyang; Xie, Ruyan; Liu, Xiaohui; Li, Haohan; Luo, Ziheng; Li, Yanbing; Chen, Fei; Zeng, Wenbin ·
RPEP-08175 · 2024The antimicrobial peptide KRWWKWIRW (identified through artificial neural network screening) was coupled with an aggregation-induced emission (AIE) photosensitizer. The conjugate demonstrated:
- Excellent killing of both gram-positive (G+) and gram-negative (G-) bacteria in vitro
- Significant destruction of MRSA biofilms
- Enhanced photoactivatable antibacterial activity against G- bacteria through bacterial aggregation
- Remarkable efficacy in treating wound infections in mice in vivo
The AIE photosensitizer fluoresces more brightly when aggregated, enabling visualization of the antibacterial mechanism in action.
Fan, Duoyang; Liu, Xiaohui; Ren, Yueming; Luo, Ziheng; Li, Yanbing; Dong, Jie; Wegner, Seraphine V; Chen, Fei; Zeng, Wenbin ·
RPEP-08177 · 2024DK-I-56-1 (a deuterated α6GABAAR-selective positive allosteric modulator) significantly reduced three markers of trigeminovascular system activation in a capsaicin-induced migraine model:
- TCC neuronal activation (c-Fos immunoreactivity)
- Trigeminal ganglion CGRP immunoreactivity elevation
- Dural CGRP depletion (indicating reduced CGRP release)
At 3 mg/kg, DK-I-56-1 was comparable in efficacy to 30 mg/kg topiramate. The effect was blocked by furosemide (a blood-brain-barrier impermeable α6GABAAR antagonist), confirming the drug works through peripheral GABA receptors, not central ones. Oral administration was also effective.
Fan, Pi-Chuan; Chiou, Lih-Chu; Lai, Tzu-Hsuan; Sharmin, Dishary; Cook, James; Lee, Ming Tatt ·
RPEP-08186 · 2024Researchers developed a simple extrusion-based method to create aligned peptide nanofiber hydrogels by applying shear force during ion-triggered gelation. By adjusting phosphate buffer concentration during self-assembly, they could tune the degree of fiber alignment and packing. More aligned hydrogels were stronger and stiffer under hydrated conditions.
When cells were grown on these scaffolds, aligned nanofibers guided directional cell spreading, but — surprisingly — increased matrix alignment did not always lead to increased cellular alignment. Nanoscale analysis revealed that cells need mechanical coupling to interpret alignment cues, not just structural alignment alone.
Farsheed, Adam C; Zevallos-Delgado, Christian; Yu, Le Tracy; Saeidifard, Sajede; Swain, Joseph W R; Makhoul, Jonathan T; Thomas, Adam J; Cole, Carson C; Huitron, Eric Garcia; Grande-Allen, K Jane; Singh, Manmohan; Larin, Kirill V; Hartgerink, Jeffrey D ·
RPEP-08188 · 2024Across 10 studies (9 RCTs and 1 retrospective cohort) encompassing 6,623 non-diabetic overweight or obese participants, semaglutide in various doses and forms demonstrated consistent, significant weight loss effects. The review examined changes in body weight, waist circumference, and the proportion of patients achieving at least 5% clinically meaningful weight loss. The consolidated evidence endorsed semaglutide as a highly efficient weight-reducing agent in people without diabetes.
Fatima, Nazeefa; Anand, Abhinav; Palvia, Aadi R; Kaur, Avneet; Azeez, Gibran A; Thirunagari, Mounika; Butt, Samia Rauf R ·
RPEP-08190 · 2024In this Phase IIa randomized, double-blind, placebo-controlled, within-subject crossover study of 42 individuals with alcohol use disorder (29 completers):
- PF-5190457 (100 mg twice daily) did NOT reduce cue-elicited alcohol craving during a bar-like laboratory experiment
- PF-5190457 did NOT influence neural activation during a cue-reactivity task in the fMRI subset (n=12)
- PF-5190457 DID reduce virtual calories selected in a cafeteria-like virtual reality environment (P=0.04)
The primary hypothesis — that blocking the ghrelin receptor would reduce alcohol craving — was not supported. However, the food-related finding provides human evidence that GHSR blockade influences caloric intake decisions.
Faulkner, Monica L; Farokhnia, Mehdi; Lee, Mary R; Farinelli, Lisa; Browning, Brittney D; Abshire, Kelly; Daurio, Allison M; Munjal, Vikas; Deschaine, Sara L; Boukabara, Selim R; Fortney, Christopher; Sherman, Garrick; Schwandt, Melanie; Akhlaghi, Fatemeh; Momenan, Reza; Ross, Thomas J; Persky, Susan; Leggio, Lorenzo ·
RPEP-08192 · 2024In obese mice fed a high-fat diet for 12 weeks then treated with semaglutide:
- Cognitive function improved significantly on the Morris water maze test
- Pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) were reduced
- Gut microbiota changes were reversed: Akkermansia, Muribaculaceae, Coriobacteriaceae_UCG_002, and Clostridia_UCG_014 (all decreased by obesity) were restored; Romboutsia, Dubosiella, and Enterorhabdus (increased by obesity) were reduced
Correlation analysis revealed:
- Muribaculaceae and Clostridia_UCG_014 positively correlated with cognitive function
- Romboutsia and Dubosiella negatively correlated with cognitive function
- Romboutsia positively correlated with inflammatory cytokines (TNF-α, IL-6, IL-1β)
- Clostridia_UCG_014 negatively correlated with inflammatory cytokines
Feng, Jing; Teng, Zhenjie; Yang, Yu; Liu, Jingzhen; Chen, Shuchun ·
RPEP-08194 · 2024Across 53 real-world studies, erenumab reduced monthly migraine days by 7.18 days and monthly headache days by 6.89 days at 3 months. HIT-6 disability scores improved by 6.97 points, medication use dropped by 6.22 days/month, and pain intensity decreased by 1.71 points. Effects increased slightly at 6 and 12 months. Approximately one-third of patients achieved >30% response, one-sixth achieved >50% response, and 3–4% became completely migraine-free. Adverse event rates were 0.34 at 6 months and 0.43 at 12 months.
Fernández-Bravo-Rodrigo, Jaime; Cavero-Redondo, Iván; Lucerón-Lucas-Torres, Maribel; Martínez-García, Irene; Flor-García, Amparo; Barreda-Hernández, Dolores; Pascual-Morena, Carlos ·
RPEP-08197 · 2024Blocking ghrelin receptor (GHSR) signaling during the perinatal period with LEAP2 (a natural ghrelin-blocking peptide) altered liver metabolism and glucose regulation in rats at puberty. LEAP2 injections during pregnancy or early postnatal life significantly impacted liver PEPCK expression — a key enzyme in glucose production — and affected glucose homeostasis in a sex- and timing-dependent manner.
Importantly, these metabolic effects occurred without changes in body weight or food intake, suggesting that early-life ghrelin signaling programs metabolic function in ways that only become apparent later in development. The authors note these effects may be the beginning of larger metabolic imbalances that could emerge in adulthood.
Ferreira-Junior, Marcos Divino; Cavalcante, Keilah Valéria Naves; Xavier, Carlos Henrique; Vanzela, Emerielle Cristine; Boschero, Antonio Carlos; Matafome, Paulo; Gomes, Rodrigo Mello · Animal Study
RPEP-08200 · 2024The review synthesizes evidence proposing a signaling pathway from oxidative stress to migraine:
1. Many migraine triggers (sleep deprivation, alcohol, hormonal changes, certain foods) increase reactive oxygen and nitrogen species (RONS)
2. TRPA1 ion channels on trigeminal nerve endings are activated by oxidative stress products
3. TRPA1 activation triggers CGRP release from nerve endings
4. Released CGRP causes vasodilation, neurogenic inflammation, and pain — the hallmarks of migraine
The authors propose TRPA1 as the critical molecular link in this pathway and as a druggable target upstream of CGRP.
Fila, Michal; Przyslo, Lukasz; Derwich, Marcin; Sobczuk, Piotr; Pawlowska, Elzbieta; Blasiak, Janusz ·