RPEP-08413 · 2024Aquafaba (the cooking water from chickpeas and beans) contains dozens of bioactive peptides and oligosaccharides. Using advanced mass spectrometry, the researchers identified 78 oligosaccharides in chickpea aquafaba and 67 in common bean aquafaba. They also discovered several γ-glutamyl peptides with known anti-inflammatory and flavor-enhancing (kokumi) properties, including γ-Glu-Phe and γ-Glu-Tyr in chickpea aquafaba, and γ-Glu-S-methyl-Cys and γ-Glu-Leu in bean aquafaba. The oligosaccharides also showed prebiotic activity, promoting the growth of beneficial gut bacteria.
Huang, Yu-Ping; Masarweh, Chad; Paviani, Bruna; Mills, David A; Barile, Daniela ·
RPEP-08415 · 2024In 67 patients hospitalized with acute heart failure and renal dysfunction, both BNP alone and BNP combined with sildenafil (PDE-V inhibitor) significantly increased plasma cGMP at 24 hours: +25.6% with BNP and +60.8% with BNP/sildenafil versus -13.5% with standard care (P=0.001).
However, this biochemical response did not translate to clinical improvement. The coprimary endpoints showed no significant differences: eGFR change was 0% (standard care) vs 0% (BNP) vs -8.8% (BNP/sildenafil) (P=0.60), and BUN change was -1.4% vs -5.9% vs +6.9% (P=0.38). Urinary sodium and cGMP excretion also did not improve. Hypotension was more common in the BNP/sildenafil group, representing a safety concern.
Hubers, Scott A; Benike, Sherry L; Johnson, Bradley K; McKie, Paul M; Scott, Christopher; Chen, Horng H ·
RPEP-08417 · 2024Oxadiazole-containing (Odz) cyclic peptides showed high cell penetration that depended on the position of specific side chains and the chloroalkane tag used for detection. NMR analysis revealed these macrocycles adopt a β-turn conformation. Intriguingly, despite high cell penetration in living cells, they showed low passive permeability in artificial membrane assays.
This discrepancy suggests these cyclic peptides enter cells through an active or energy-dependent mechanism rather than simply diffusing through cell membranes — an important finding for understanding and designing cell-penetrant macrocyclic peptides.
Huh, Sungjoon; Batistatou, Nefeli; Wang, Jing; Saunders, George J; Kritzer, Joshua A; Yudin, Andrei K ·
RPEP-08425 · 2024Anti-CGRP monoclonal antibodies were safe and effective when used alongside other monoclonal antibodies for different conditions. In 38 migraine patients taking both an anti-CGRP mAb and another mAb, monthly headache days decreased significantly at 3 months (p<0.0001) and 6 months (p<0.001), along with improvements in disability (MIDAS) and impact (HIT-6) scores. Only 15.8% of patients experienced mild adverse events from the combination, and only one patient discontinued due to side effects. At 6 months, 48.3% of patients reported meaningful improvement on the global impression of change scale.
Iannone, Luigi Francesco; Romozzi, Marina; Russo, Antonio; Saporito, Gennaro; De Santis, Federico; Ornello, Raffaele; Sances, Grazia; Vaghi, Gloria; Tassorelli, Cristina; Albanese, Maria; Guerzoni, Simona; Casalena, Alfonsina; Vollono, Catello; Calabresi, Paolo; Prudenzano, Maria Pia; Mampreso, Edoardo; Volta, Giorgio Dalla; Valente, Maria Rosaria; Avino, Gianluca; Chiarugi, Alberto; Sacco, Simona; Pistoia, Francesca ·
RPEP-08431 · 2024Among 937 patients who underwent LAAC (98% successful implantation rate), the common logarithm of baseline plasma BNP was independently associated with the composite primary outcome (death or stroke/bleeding events) with an adjusted hazard ratio of 1.46 (95% CI: 1.06-2.18, p = 0.043). A calculated BNP cutoff of 133 pg/mL significantly stratified outcomes: 29% vs 21% cumulative incidence of the primary outcome at 2 years (p = 0.004). Over a median follow-up of 366 days, 148 patients experienced a primary outcome event.
Imamura, Teruhiko; Kataoka, Naoya; Tanaka, Shuhei; Ueno, Hiroshi; Kinugawa, Koichiro; Nakashima, Masaki; Yamamoto, Masanori; Sago, Mitsuru; Chatani, Ryuki; Asami, Masahiko; Hachinohe, Daisuke; Naganuma, Toru; Ohno, Yohei; Tani, Tomoyuki; Okamatsu, Hideharu; Mizutani, Kazuki; Watanabe, Yusuke; Izumo, Masaki; Saji, Mike; Mizuno, Shingo; Kubo, Shunsuke; Shirai, Shinichi; Hayashida, Kentaro ·
RPEP-08438 · 2024Amnion-derived mesenchymal stem cells (AMSCs) cultured under hypoxic conditions (1% O2) produced higher levels of the antimicrobial peptide LL-37 compared to normal oxygen conditions (21% O2). The hypoxic conditioned medium significantly inhibited S. aureus growth in vitro.
When delivered as a hydrogel to S. aureus-infected skin wounds in diabetic mice, the hypoxic conditioned medium reduced bacterial counts in the wounds and facilitated wound closure. This dual antimicrobial and wound-healing effect was mediated at least in part by the elevated LL-37 levels.
Ishii, Riku; Ohnishi, Shunsuke; Hojo, Masahiro; Ishikawa, Kosuke; Funayama, Emi; Miura, Takahiro; Okubo, Naoto; Okada, Kazufumi; Yamamoto, Yuhei; Maeda, Taku ·
RPEP-08441 · 2024Neuropeptide Y, a 36-amino-acid polypeptide neurotransmitter, acts through a family of G-protein-coupled receptors with six subtypes (Y1-Y6), of which Y1, Y2, Y4, and Y5 are functional in humans. The Y1 receptor plays particularly important roles in immune responses across multiple organs including the respiratory system.
NPY and the Y1 receptor have critical roles in the pathogenesis of asthma, COPD, and idiopathic pulmonary fibrosis. Notably, the effects of NPY on airway immune responses and disease pathogenesis differ among these respiratory conditions, indicating that NPY's influence is disease-specific rather than following a single unified mechanism.
Itano, Junko; Kiura, Katsuyuki; Maeda, Yoshinobu; Miyahara, Nobuaki ·
RPEP-08446 · 2024In participants switching from stable GLP-1 RA treatment to tirzepatide 5 mg:
- HbA1c decreased by -0.43% at 12 weeks (p<0.01)
- Fasting serum glucose decreased by -7.83 mg/dL (p<0.01)
- Body weight decreased by -2.15 kg (p<0.01)
- Improvements occurred across all baseline GLP-1 RA subgroups (semaglutide, dulaglutide, liraglutide)
- 13.2% (20 participants) developed gastrointestinal events
- 2% (3 participants) discontinued due to adverse events
- No severe hypoglycemia or deaths
Baseline characteristics: mean age 58.3 years, HbA1c 7.39%, BMI 35.18 kg/m², T2D duration ~12.4 years, 55% female. Most were switching from semaglutide 1.0 mg (55%) or dulaglutide 1.5 mg (42%).
Jabbour, Serge; Paik, Jim S; Aleppo, Grazia; Sharma, Palash; Gomez Valderas, Elisa; Benneyworth, Brian D ·
RPEP-08447 · 2024The researchers determined the 3D solution structures of both AKH and ACP hormones using NMR spectroscopy, then built atomic-scale models of their G protein-coupled receptors using homology modeling. Blind docking simulations identified how each hormone binds to its specific receptor.
The models explained why these two systems are exclusive — each receptor only binds its own hormone, not the other. Validation against existing experimental data showed largely acceptable agreement, confirming the models are usable for future drug discovery. The study noted that distinguishing true agonists from antagonists may require additional experimental testing.
Jackson, Graham E; Sani, Marc-Antoine; Marco, Heather G; Separovic, Frances; Gäde, Gerd ·
RPEP-08456 · 2024While GLP-1 and GIP receptor agonists have shown unprecedented benefits — blood sugar control, weight loss, reduced cardiovascular and renal risks, and even diabetes prevention from prediabetes — the review raises serious questions about long-term sustainability. Chronic stimulation of pancreatic β-cells may lead to receptor downregulation and β-cell exhaustion, potentially causing β-cell failure over time. The longest randomized trial data available is only 3 years.
The review also discusses emerging approaches including amylin (which suppresses appetite but can self-aggregate and cause cytotoxicity) and triple agonists combining GLP-1, GIP, and glucagon activity.
Janket, Sok-Ja; Chatanaka, Miyo K; Sohaei, Dorsa; Tamimi, Faleh; Meurman, Jukka H; Diamandis, Eleftherios P ·
RPEP-08461 · 2024In 22 chronic migraine patients who responded to anti-CGRP monoclonal antibody treatment, median daily steps increased significantly from 4,421 to 5,241 (p=0.039) — an 18.5% increase. The increase in daily steps positively correlated with treatment response measured by reduction in monthly migraine days (p=0.013), suggesting that step count could serve as an objective, passively collected marker of treatment effectiveness.
Jantzen, Frederik Thal; Chaudhry, Basit Ali; Younis, Samaira; Nørgaard, Ina; Cullum, Christopher Kjaer; Do, Thien Phu; Beier, Dagmar; Amin, Faisal Mohammad ·
RPEP-08464 · 2024From computational protease cleavage prediction, researchers identified candidate tetrapeptides and tested them on cultured human dermal fibroblasts. All applied peptides triggered cellular responses, but the effects were highly sequence-dependent.
Two peptides — GPKG (glycine-proline-lysine-glycine) and LSVD (leucine-serine-valine-aspartate) — were selected for further characterization based on bioactivity, low toxicity, and protein source. In vitro, they enhanced transcription of matrix organization and cell proliferation genes. In a short-term patch test, they promoted processes associated with epithelial and dermal maintenance and remodeling. In a longer-term split-face clinical study, prolonged use of a formulation containing both peptides led to significantly improved measures of crow's feet and skin firmness in a mixed population.
Jariwala, Nathan; Ozols, Matiss; Eckersley, Alexander; Mambwe, Bezaleel; Watson, Rachel E B; Zeef, Leo; Gilmore, Andrew; Debelle, Laurent; Bell, Mike; Bradley, Eleanor J; Doush, Yegor; Keenan, Amy; Courage, Carole; Leroux, Richard; Peschard, Olivier; Mondon, Philippe; Ringenbach, Caroline; Bernard, Laure; Pitois, Aurelien; Sherratt, Michael J ·
RPEP-08468 · 2024Substance P levels in gingival crevicular fluid are highest in areas with active periodontal disease and bone loss. SP contributes to periodontal pathology through multiple mechanisms: triggering neurogenic inflammation, modulating immune responses, promoting bone resorption, and sustaining pain in vulnerable tissues. SP expression during disease progression may represent a risk factor for systemic inflammatory diseases like chronic arthritis. SP also plays roles in tissue regeneration, suggesting it could be both a therapeutic target and a regenerative tool.
Jayanthi, A; Tiwari, D; Puzhankara, L ·
RPEP-08481 · 2024Transcutaneous gastric pacing (TGP) significantly improved gastrointestinal recovery in early-stage acute pancreatitis patients compared to conventional treatment. The TGP group had shorter time to first bowel movement (p<0.05) and fewer hospital days (p<0.05). Mechanistically, TGP decreased serum vasoactive intestinal peptide (VIP) levels (p<0.05), increased normal gastric slow waves (p<0.05), and reduced the inflammatory marker IL-6 (p<0.05).
Autonomic nervous system testing revealed TGP increased vagal (parasympathetic) activity while decreasing sympathetic activity (both p<0.01), suggesting the treatment works by restoring autonomic balance through vagal stimulation, which in turn normalizes gastrointestinal peptide signaling.
Jia, Zhenyu; Kong, Lingchao; Lu, Xiaochun; Lu, Jianying; Shen, Yuying; Qiao, Zhenguo; Xia, Tingting · Rct
RPEP-08483 · 2024Bullfrog GLP-1 (bGLP-1) showed the highest potency among natural GLP-1 analogues screened from fish and amphibians. Through structure-activity optimization and long-acting modifications, the researchers created analogue 2f, which showed superior effects on food intake, glycemic control, and body weight compared to semaglutide.
Using the bGLP-1 sequence as a scaffold, they also designed dual GLP-1/glucagon receptor agonist (3o) and triple GLP-1/GIP/glucagon receptor agonist (4b), both of which demonstrated significant therapeutic effects on lipid regulation, glycemic control, and body weight in preclinical testing.
Jiang, Neng; Su, Di; Chen, De; Huang, Shutong; Tang, Chunli; Jing, Lin; Yang, Caiyan; Zhou, Zhongbo; Yan, Zhiming; Han, Jing ·
RPEP-08486 · 2024After 24 weeks, exenatide plus metformin (Group B) was significantly superior to metformin alone (Group A) across all measured outcomes: fasting blood glucose, postprandial glucose, triglycerides, total cholesterol, ALT, and AST were all lower in the combination group (p<0.001 for all).
The combination also significantly improved intestinal flora: counts of harmful bacteria (E. coli and Enterococcus faecalis) were lower (p<0.05), while beneficial bacteria (Bifidobacteria and Lactobacillus) were higher (p<0.05) in the combination group. This suggests exenatide and metformin have synergistic effects on metabolic, hepatic, and microbiome parameters.
Jiang, Xiaojie; Shi, Tingting; Han, Dan; Chen, Juan ·
RPEP-08494 · 2024The cell-penetrating peptide TAT enabled efficient loading of biologic drugs into milk-derived extracellular vesicles (EVs) and protected them from degradation in the gastrointestinal tract both in vitro and in vivo.
Oral delivery of EVs loaded with the anti-TNF-α nanobody VHHm3F (EVVHH) significantly reduced tissue TNF-α levels and alleviated pathology in mice with acute ulcerative colitis, outperforming the nanobody delivered alone. In chronic UC, EVs simultaneously loaded with both VHH and the antimicrobial peptide LL37 (EVLV) improved the intestinal barrier, reduced inflammation, rebalanced the gut microbiota, and relieved UC-induced depression and anxiety. The TAT-mediated loading approach was described as simple and generalizable to other diseases.
Jing, Renwei; Zhang, Leijie; Li, Ruibin; Yang, Zhongqiu; Song, Jun; Wang, Qian; Cao, Nan; Han, Gang; Yin, HaiFang ·
RPEP-08498 · 2024The researchers tested whether current computational tools can accurately predict how short peptides self-assemble into 3D structures like hydrogels. Using a technique called MELD (Modeling Employing Limited Data) combined with molecular dynamics simulations, they were able to drive self-assembly predictions when standard simulations failed.
Critically, they found that current machine learning algorithms — including the breakthrough protein structure prediction tools — are not yet suited for predicting the assembly of short peptides. This gap means computational design of peptide biomaterials still requires specialized physical modeling approaches rather than off-the-shelf AI tools.
Jones, Stephen J; Perez, Alberto · Computational
RPEP-08499 · 2024A patient with previously undiagnosed VIPoma was found to have tricuspid regurgitation and stenosis on echocardiography — cardiac valve changes typically associated with classical carcinoid syndrome but not historically seen with VIP-secreting tumors. The echocardiographic finding of carcinoid heart disease prompted the workup that ultimately led to the VIPoma diagnosis.
This is notable because VIPomas have an incidence of only 0.05%–2% of neuroendocrine tumors, and cardiac valve involvement has not been a recognized feature of these tumors. The case suggests that the spectrum of neuroendocrine tumors capable of causing carcinoid heart disease may be wider than previously understood.
Joshi, Mugdha; Aldea, Daniel; Ngo, Peter; Shah, Sonia · Case Report
RPEP-08501 · 2024Peptides are being used to solve two of glioblastoma's biggest treatment challenges: getting drugs across the blood-brain barrier (BBB) and targeting them specifically to tumor cells. Tumor-homing peptides can be attached to liposomes (nano-sized drug carriers) to create guided delivery systems that cross the BBB, recognize receptors overexpressed on glioblastoma cells, and penetrate deep into the tumor.
Preclinical studies show these peptide-functionalized liposomes increase drug accumulation in tumors and produce strong antitumor effects. However, major obstacles remain: manufacturing is difficult, characterizing the nanosystems is complex, and antibody-based approaches are competitive alternatives.
Jourdain, M-A; Eyer, J · Review
RPEP-08508 · 2024In the STEP 6 trial subgroup analysis, semaglutide 2.4 mg produced clinically meaningful weight loss across all demographic subgroups in a Japanese and Korean population, with estimated mean weight changes ranging from -9.40% to -16.42% over 68 weeks. Both semaglutide doses outperformed placebo.
Notably, sex significantly affected the response — the treatment-by-sex interaction was highly significant for both doses (p=0.0008 and p=0.0005). Having type 2 diabetes or dyslipidemia at baseline also significantly modified the response to the higher 2.4 mg dose. Despite these variations, semaglutide worked across all subgroups examined.
Kadowaki, Takashi; Lee, Sang Yeoup; Ogawa, Wataru; Nishida, Tomoyuki; Overvad, Maria; Tobe, Kazuyuki; Yamauchi, Toshimasa; Lim, Soo · Rct Subgroup
RPEP-08518 · 2024In 10,855 adults with autoimmune inflammatory diseases and type 2 diabetes, initiating GLP-1 receptor agonists was associated with 52% lower all-cause mortality (HR 0.48, 95% CI 0.31-0.75) and 34% lower major adverse cardiovascular events (HR 0.66, 95% CI 0.50-0.88) compared to DPP-4 inhibitors. This translated to 9.4 fewer deaths and 10.5 fewer cardiovascular events per 1,000 person-years. The benefit was similar in matched adults without autoimmune diseases.
Karacabeyli, Derin; Lacaille, Diane; Lu, Na; McCormick, Natalie; Xie, Hui; Choi, Hyon K; Aviña-Zubieta, J Antonio ·
RPEP-08527 · 2024The review covers the blood pressure effects of all major approved obesity therapies. GLP-1 receptor agonists (liraglutide and semaglutide) and tirzepatide — peptide-based therapies — are among the treatments examined for their impact on hypertension. The shared pathophysiology linking obesity and hypertension includes overactivity of the renin-angiotensin-aldosterone system (RAAS) and sympathetic nervous system, insulin resistance, and disruption of the leptin pathway.
The review presents clinical evidence for how each therapy modifies blood pressure, positioning weight loss as a dual-benefit strategy for managing both obesity and hypertension simultaneously.
Katsi, Vasiliki; Manta, Eleni; Fragoulis, Christos; Tsioufis, Konstantinos ·
RPEP-08528 · 2024Researchers developed an ensemble computational method that can predict whether a peptide sequence functions as a hormone with 89.79% accuracy and an AUROC of 0.96. The approach combines similarity-based methods (BLAST, MERCI) with machine learning models (logistic regression achieving AUROC 0.93 alone). The ensemble method overcame limitations of similarity-based methods, which sometimes couldn't make predictions for novel sequences.
The team built a free web tool called HOPPred that can identify hormone-associated motifs within peptide sequences, making the prediction method accessible to researchers without computational expertise.
Kaur, Dashleen; Arora, Akanksha; Vigneshwar, Palani; Raghava, Gajendra P S · Computational
RPEP-08534 · 2024The review synthesizes evidence showing multiple neuroprotective and anti-inflammatory effects of GLP-1 receptor agonists relevant to MS:
- In animal models of experimental autoimmune encephalopathy (the standard MS model), GLP-1 agonists significantly delayed symptom onset and reduced disease severity
- Treatment increased nerve myelination and brain weight in these models
- In nerve crush injury models, GLP-1 agonists significantly increased the rate and density of nerve regeneration compared to controls
- The mechanism likely involves GLP-1 receptors present on immune cells (macrophages, monocytes, lymphocytes), allowing the drugs to modulate inflammatory responses
The authors conclude that GLP-1 agonists show promise as both prophylactic and symptomatic treatments for MS.
Kaye, Alan D; Sala, Kelly R; Abbott, Brennan M; Dicke, Alexandra N; Johnson, Landyn D; Wilson, Parker A; Amarasinghe, Sam N; Singh, Naina; Ahmadzadeh, Shahab; Kaye, Adam M; Shekoohi, Sahar; Varrassi, Giustino ·
RPEP-08540 · 2024Across 3,136 participants from three randomized controlled trials, semaglutide 2.4 mg produced an overall systolic blood pressure reduction of -4.95 mmHg (95% CI -5.86 to -4.05) compared to placebo over 68 weeks.
Importantly, the blood pressure reductions in people with hypertension (-4.78 mmHg) were similar to the overall population, rather than being larger as the researchers hypothesized. Those on semaglutide also reduced their anti-hypertensive medication intensity compared to placebo (score difference -0.51), suggesting that some of the blood pressure benefit may have been masked by concurrent medication reductions.
Kennedy, Cormac; Hayes, Peter; Cicero, Arrigo F G; Dobner, Stephan; Le Roux, Carel W; McEvoy, John W; Zgaga, Lina; Hennessy, Martina ·
RPEP-08546 · 2024The review establishes that nose-to-brain (N2B) delivery pathways — primarily along the olfactory and trigeminal nerves — can transport GLP-1 receptor agonists directly to brain regions involved in appetite regulation, circumventing the blood-brain barrier that limits subcutaneous delivery.
Key challenges for nasal peptide delivery include nasal physiological barriers (mucociliary clearance, enzymatic degradation, limited epithelial permeability) and the peptide's physicochemical properties (size, charge, stability). Promising strategies to overcome these include cell permeation enhancers, mucoadhesive formulations that extend contact time with nasal epithelium, and nanocarrier systems. The review emphasizes that while preclinical results are encouraging, clinical effectiveness has not yet been demonstrated for this route of GLP-1 delivery.
Khan, Tanisha Tabassum Sayka; Sheikh, Zara; Maleknia, Simin; Oveissi, Farshad; Fathi, Ali; Abrams, Terence; Ong, Hui Xin; Traini, Daniela ·
RPEP-08548 · 2024Liraglutide (30 μg/kg/day) and/or resveratrol (20 mg/kg/day) given alongside cyclosporine A (25 mg/kg/day for 21 days) significantly improved kidney function tests and antioxidant activity in treated rats. Both treatments enhanced Bcl-2 levels (anti-apoptotic) while downregulating Bax (pro-apoptotic) in cyclosporine-treated kidneys. TNF-α immunostaining was negative to mildly positive in treated groups versus strongly positive in the cyclosporine-only group, confirming anti-inflammatory effects. Combination treatment (liraglutide + resveratrol) showed benefit across all measured markers.
Kheira, Hend Samy; Elsayed, Gehad Ramadan; El-Adl, Mohamed ·
RPEP-08549 · 2024Over 5.2 million patient-years of follow-up with 25,982 three-point MACE events: GLP-1RAs showed lower 3-point MACE risk than DPP4is (HR: 0.83, 95% CI: 0.70-0.98) and SUs (HR: 0.72, 95% CI: 0.58-0.88). SGLT2is showed similar patterns vs DPP4is (HR: 0.89, 95% CI: 0.79-1.00) and SUs (HR: 0.76, 95% CI: 0.65-0.89). No significant difference between SGLT2is and GLP-1RAs (HR: 1.06, 95% CI: 0.96-1.17). Same hierarchy for 4-point MACE (adding heart failure hospitalization). DPP4is outperformed SUs (HR: 0.87, 95% CI: 0.79-0.95).
Khera, Rohan; Aminorroaya, Arya; Dhingra, Lovedeep Singh; Thangaraj, Phyllis M; Pedroso Camargos, Aline; Bu, Fan; Ding, Xiyu; Nishimura, Akihiko; Anand, Tara V; Arshad, Faaizah; Blacketer, Clair; Chai, Yi; Chattopadhyay, Shounak; Cook, Michael; Dorr, David A; Duarte-Salles, Talita; DuVall, Scott L; Falconer, Thomas; French, Tina E; Hanchrow, Elizabeth E; Kaur, Guneet; Lau, Wallis C Y; Li, Jing; Li, Kelly; Liu, Yuntian; Lu, Yuan; Man, Kenneth K C; Matheny, Michael E; Mathioudakis, Nestoras; McLeggon, Jody-Ann; McLemore, Michael F; Minty, Evan; Morales, Daniel R; Nagy, Paul; Ostropolets, Anna; Pistillo, Andrea; Phan, Thanh-Phuc; Pratt, Nicole; Reyes, Carlen; Richter, Lauren; Ross, Joseph S; Ruan, Elise; Seager, Sarah L; Simon, Katherine R; Viernes, Benjamin; Yang, Jianxiao; Yin, Can; You, Seng Chan; Zhou, Jin J; Ryan, Patrick B; Schuemie, Martijn J; Krumholz, Harlan M; Hripcsak, George; Suchard, Marc A ·
RPEP-08550 · 2024Peptibodies (peptide-Fc fusions) overcome key limitations of therapeutic peptides — including low stability, rapid clearance, and poor absorption — by fusing bioactive peptides to the Fc domain of immunoglobulin. This fusion enhances half-life, stability against proteolytic digestion, and overall efficacy while retaining the peptide's advantages of tissue penetration, cellular internalization, and low immunogenicity. Two peptibodies have achieved regulatory approval: romiplostim (EMA/FDA, for thrombocytopenia) and dulaglutide (FDA, a GLP-1 receptor agonist for type 2 diabetes).
Khezri, Hamidhossein; Mostafavi, Mahdiyeh; Dabirmanesh, Bahareh; Khajeh, Khosro ·
RPEP-08554 · 2024The review covers several key aspects of peptide nanostructure-based drug delivery:
- Synthesis and self-assembly techniques: peptides and proteins can form diverse nanostructures (nanotubes, fibers, micelles, vesicles) with tunable properties
- Design strategies for enhanced stability, drug-loading capacity, and controlled release
- Cell interaction mechanisms: receptor-mediated endocytosis and cell-penetrating capabilities enable targeted delivery
- Biocompatibility and biomolecular recognition capacity make peptides ideal drug carriers
- Applications in precision medicine: personalized therapies and disease-specific targeting for diagnostics and therapeutics
- Cancer applications: tumor-specific targeting and delivery of therapeutic payloads
Kim, HaRam; Taslakjian, Boghos; Kim, Sarah; Tirrell, Matthew V; Guler, Mustafa O ·
RPEP-08556 · 2024GLP-1RA administration to patients with obesity produced heightened preingestive satiation — feeling full before eating. Analysis of human and mouse brain tissue identified GLP-1 receptor neurons in the dorsomedial hypothalamus (DMH) as the key mediators.
Optogenetic activation of DMH GLP-1R neurons directly caused satiation in mice. Calcium imaging showed these neurons actively encode preingestive satiation signals. GLP-1RA administration specifically increased DMH GLP-1R neuron activity during eating behavior. The mechanism involves interplay between DMH GLP-1R neurons and NPY/AgRP neurons in the arcuate nucleus — the brain's primary hunger-promoting neurons.
Kim, Kyu Sik; Park, Joon Seok; Hwang, Eunsang; Park, Min Jung; Shin, Hwa Yun; Lee, Young Hee; Kim, Kyung Min; Gautron, Laurent; Godschall, Elizabeth; Portillo, Bryan; Grose, Kyle; Jung, Sang-Ho; Baek, So Lin; Yun, Young Hyun; Lee, Doyeon; Kim, Eunseong; Ajwani, Jason; Yoo, Seong Ho; Güler, Ali D; Williams, Kevin W; Choi, Hyung Jin ·
RPEP-08558 · 2024Low molecular weight collagen peptide (LMWCP) from fish promoted hair growth across multiple experimental models: it stimulated human dermal papilla cell proliferation and mitochondrial activity, increased secretion of growth factors (EGF, HB-EGF, FGF-4, FGF-6), boosted new hair follicle formation in a dose-dependent manner in patch assays, promoted human hair follicle growth ex vivo, and significantly stimulated hair growth when given orally to mice. The mechanism involved activation of the Wnt/GSK-3β/β-catenin signaling pathway, with upregulation of Wnt3a, β-catenin, VEGF, PCNA, Cyclin D1, and hair-specific keratins.
Kim, Yujin; Lee, Jung Ok; Lee, Jung Min; Lee, Mun-Hoe; Kim, Hyeong-Min; Chung, Hee-Chul; Kim, Do-Un; Lee, Jin-Hee; Kim, Beom Joon ·
RPEP-08560 · 2024SGLT-2 inhibitors and GLP-1 receptor agonists provide cardiovascular and renal protection beyond glucose lowering, reduce body weight and hypoglycemia risk, and improve diabetes-related distress, physical function, and health-related quality of life. Combined with basal insulin/GLP-1RA combinations, they enable treatment simplification from high-dose multi-injection insulin regimens. Additional benefits include reduced incidence of depression, cognitive decline, respiratory disease, gout, and arrhythmias — addressing the multimorbidity burden that complicates type 2 diabetes and degrades quality of life.
Kintzoglanakis, Kyriakos; Diamantis, Christos; Mariolis, Anargiros; Paschou, Stavroula A ·
RPEP-08562 · 2024CSD triggers activation of the trigeminal nervous system and upregulates calcitonin gene-related peptide (CGRP) expression, establishing a direct mechanistic link between migraine aura and migraine pain. The review synthesizes evidence showing that CSD causes ionic changes and excitotoxicity in neurons and glia, which then propagate signals to the trigeminal system. Factors including genetics, obesity, and environmental conditions influence the threshold for CSD, representing potential therapeutic targets. Current CGRP-targeting drugs are evaluated for their expected ability to suppress CSD-related activity, and emerging therapies including intranasal insulin-like growth factor 1 and vagus nerve stimulation show promise in reducing CSD susceptibility.
Kitamura, Eiji; Imai, Noboru ·
RPEP-08565 · 2024NPY levels were positively associated with mean arterial pressure (β = 1.63, P = 0.002), total action potential clusters (β = 0.90, P = 0.005), and action potential frequency (β = 0.11, P = 0.003). This shows that both the rate of nerve firing and the pattern of nerve fiber recruitment regulate NPY release.
Norepinephrine levels were also positively related to AP clusters (β = 19.50, P = 0.030) and AP frequency (β = 2.66, P = 0.014) but notably were not significantly related to mean arterial pressure (P = 0.133). This distinction suggests that NPY, rather than norepinephrine alone, may be the neurotransmitter more closely linked to blood pressure regulation through sympathetic nerve activity patterns.
Klassen, Stephen A; Limberg, Jacqueline K; Harvey, Ronée E; Wiggins, Chad C; Spafford, Julia E; Iannarelli, Nathaniel J; Senefeld, Jonathon W; Nicholson, Wayne T; Curry, Timothy B; Joyner, Michael J; Shoemaker, J Kevin; Baker, Sarah E ·
RPEP-08569 · 2024Acute exenatide (1 μg/kg subcutaneous) administered 1 hour before the first feeding session reduced food intake to uniformly very low levels across all meal schedule conditions, completely eliminating the anticipatory effect — where monkeys normally eat less in session 1 when expecting preferred food in session 2.
Exenatide induced hypoglycemia in a meal-schedule-dependent anticipatory pattern, suggesting metabolic anticipation was preserved even as eating behavior was suppressed. In the second feeding session, the positive contrast effect (preference for tastier food) was preserved but with a weaker residual effect specifically on consumption of the more palatable pellet. The authors conclude exenatide's effects evolve temporally from strong anorectic (appetite-suppressing) to weak anhedonic (pleasure-dampening) modulation.
Knakker, Balázs; Inkeller, Judit; Kovács, Péter; Lendvai, Balázs; Hernádi, István ·
RPEP-08571 · 2024Three PWS patients without diabetes received semaglutide (0.5-2 mg weekly) with long-term follow-up. Patient 1: weight maintenance with prevention of further gain. Patient 2: 14.4% weight loss from baseline. Patient 3: 11% weight loss from baseline. One patient had previously undergone metabolic surgery.
Semaglutide was well tolerated across all patients, including post-bariatric surgery. The variable response reflects the complex pathophysiology of PWS obesity, where dysfunction in satiety pathways, reward circuits, and hormonal regulation all contribute.
Koceva, Andrijana; Mlekuš Kozamernik, Katarina; Janež, Andrej; Herman, Rok; Ferjan, Simona; Jensterle, Mojca ·
RPEP-08572 · 2024All four anti-CGRP monoclonal antibodies demonstrated invariably high and consistent efficacy, with NNTs (number needed to treat) ranging from 5 to 8 for achieving a 50% reduction in monthly migraine days. This means that for every 5-8 patients treated, one additional patient achieves meaningful improvement compared to placebo.
In contrast, onabotulinumtoxin A (Botox) showed a non-significant absolute risk difference with an NNT of 56 — meaning far more patients need treatment to achieve the same benefit. Topiramate results were contradictory between its two included studies (NNTs of 2 and 22). Safety profiles were similar across all treatments, with no significant differences in serious adverse events or study dropout rates among anti-CGRP mAbs.
Kodounis, Michalis; Constantinidis, Theodoros S; Rizonaki, Konstantina; Drakou, Eleni; Zintzaras, Elias; Stefanidis, Ioannis; Mitsikostas, Dimos-Dimitrios; Dardiotis, Efthimios ·
RPEP-08573 · 2024Researchers developed a modular "plug and play" method for synthesizing grafted cyclotides — plant-derived cyclic peptides used as scaffolds for drug design. The new approach bypasses the major bottleneck of oxidative folding by grafting bioactive sequences onto a pre-formed acyclic cyclotide-like scaffold.
Using this method, the team successfully produced cyclotide variants that target G protein-coupled receptors (GPCRs) with nanomolar affinities and potencies. The technique also enabled grafting of complex epitopes with additional disulfide bonds that were previously inaccessible through conventional chemical synthesis methods.
Koehbach, Johannes; Muratspahić, Edin; Ahmed, Zakaria M; White, Andrew M; Tomašević, Nataša; Durek, Thomas; Clark, Richard J; Gruber, Christian W; Craik, David J · Laboratory/Methods Development
RPEP-08586 · 2024In type 2 diabetic rats, the GLP-1 agonist exenatide showed more pronounced antidiabetic effects than either empagliflozin (an SGLT2 inhibitor) or quercetin (a plant flavonoid) when used alone. However, the triple combination of all three drugs produced the best overall results.
All treatments lowered glucose, HbA1c, and triglyceride levels. Exenatide and the combination therapy were the only treatments to increase insulin levels. The combination was uniquely effective at decreasing leptin levels and HOMA-IR (insulin resistance). Exenatide improved HDL cholesterol and LDL levels, while the combination therapy showed the strongest combined antidiabetic and lipid-lowering effects.
Korkmaz, Yasemin; Dik, Burak · Animal
RPEP-08591 · 2024In 616 randomized patients with HFpEF, obesity (BMI ≥30), and type 2 diabetes over 52 weeks:
Primary endpoints:
- KCCQ-CSS (symptoms/function): +13.7 vs +6.4 points; difference 7.3 points (95% CI: 4.1–10.4; P < 0.001)
- Body weight: -9.8% vs -3.4%; difference -6.4 percentage points (95% CI: -7.6 to -5.2; P < 0.001)
Confirmatory secondary endpoints:
- 6-minute walk distance: +14.3 m difference (95% CI: 3.7–24.9; P = 0.008)
- Hierarchical composite (death, HF events, KCCQ-CSS, walk distance): win ratio 1.58 (P < 0.001)
- CRP level: treatment ratio 0.67 (P < 0.001) — 33% greater reduction in inflammation
- Serious adverse events: 17.7% semaglutide vs 28.8% placebo — fewer with semaglutide
Kosiborod, Mikhail N; Petrie, Mark C; Borlaug, Barry A; Butler, Javed; Davies, Melanie J; Hovingh, G Kees; Kitzman, Dalane W; Møller, Daniél V; Treppendahl, Marianne B; Verma, Subodh; Jensen, Thomas J; Liisberg, Karoline; Lindegaard, Marie L; Abhayaratna, Walter; Ahmed, Fozia Z; Ben-Gal, Tuvia; Chopra, Vijay; Ezekowitz, Justin A; Fu, Michael; Ito, Hiroshi; Lelonek, Małgorzata; Melenovský, Vojtěch; Merkely, Bela; Núñez, Julio; Perna, Eduardo; Schou, Morten; Senni, Michele; Sharma, Kavita; van der Meer, Peter; Von Lewinski, Dirk; Wolf, Dennis; Shah, Sanjiv J ·
RPEP-08592 · 2024Among 3,743 patients with HFpEF pooled from four randomized trials, semaglutide significantly reduced:
- Cardiovascular death or worsening heart failure events: 5.4% vs 7.5% (HR 0.69, 95% CI 0.53-0.89, p=0.0045) — a 31% risk reduction
- Worsening heart failure events alone: 2.8% vs 4.7% (HR 0.59, 95% CI 0.41-0.82, p=0.0019) — a 41% risk reduction
Cardiovascular death alone was not significantly reduced (3.1% vs 3.7%, HR 0.82, p=0.25). Serious adverse events were lower with semaglutide (29.9% vs 38.7%).
Kosiborod, Mikhail N; Deanfield, John; Pratley, Richard; Borlaug, Barry A; Butler, Javed; Davies, Melanie J; Emerson, Scott S; Kahn, Steven E; Kitzman, Dalane W; Lingvay, Ildiko; Mahaffey, Kenneth W; Petrie, Mark C; Plutzky, Jorge; Rasmussen, Søren; Rönnbäck, Cecilia; Shah, Sanjiv J; Verma, Subodh; Weeke, Peter E; Lincoff, A Michael ·
RPEP-08598 · 2024Floatation therapy (Float-REST) did not significantly change endogenous opioid peptide levels compared to a passive control recovery after heavy resistance exercise. Beta-endorphin (β-End) rose significantly after the intense squat workout in both conditions — as expected — but floatation therapy didn't produce any additional increase or differential pattern.
Proenkephalin (ProEnk), a precursor to the enkephalin family of opioid peptides, showed no significant changes in response to either the exercise or the floatation recovery. Its plasma levels remained detectable and stable throughout, suggesting it may function through local (paracrine) rather than systemic signaling.
The practical takeaway: the deep relaxation people commonly report from float tanks after exercise is probably not driven by changes in circulating opioid peptides. Beta-endorphin stayed consistently elevated from the workout itself regardless of recovery method.
Kraemer, William J; Caldwell, Lydia K; Post, Emily M; Volek, Jeff S; Hagen, Josh M; Newton, Robert U; Häkkinen, Keijo; Omonije, Oluseun; Maresh, Carl M · Crossover Trial
RPEP-08602 · 2024Across 8 studies (27,639 patients), GLP-1 RAs in advanced CKD/ESKD patients showed:
- Significant reduction in cardiothoracic ratio (SMD -1.2%, 95% CI -2.0 to -0.4)
- Significant reduction in pro-BNP (SMD -335.9 pmol/L, 95% CI -438.9 to -232.8)
- Significant decrease in mean blood glucose (SMD -1.1 mg/dL, 95% CI -1.8 to -0.3)
- Significant weight loss (SMD -2.2 kg, 95% CI -2.9 to -1.5)
- No significant change in systolic blood pressure or one-year mortality
Safety: GLP-1 RAs were associated with 3.8x higher risk of nausea and 35.7x higher risk of vomiting, but no significant increase in hypoglycemia risk.
Krisanapan, Pajaree; Sanpawithayakul, Kanokporn; Pattharanitima, Pattharawin; Thongprayoon, Charat; Miao, Jing; Mao, Michael A; Suppadungsuk, Supawadee; Tangpanithandee, Supawit; Craici, Iasmina M; Cheungpasitporn, Wisit ·
RPEP-08605 · 2024Among 142 patients with chronic migraine and medication overuse headache (MOH), treatment with abrupt medication withdrawal, conventional preventive therapy, and optional anti-CGRP monoclonal antibodies produced significant long-term improvements. Patients started with an average of 25.2 headache days per month.
At one-year follow-up, 51.4% of patients achieved a ≥75% reduction in headache days per month (HDM). By the five-year follow-up, this improved to 70.4% achieving ≥75% reduction in HDM, demonstrating that outcomes continued to improve over time with sustained treatment.
Krymchantowski, Abouch; Jevoux, Carla; Krymchantowski, Ana Gabriela; Dominguez-Moreno, Rogelio; Pereira Silva-Néto, Raimundo ·
RPEP-08613 · 2024In 133 men (mean age 77.7 years) with nocturnal polyuria treated with desmopressin 50 μg:
- 87.6% showed improved symptoms at 52 weeks (score ≤ 3)
- Improvements sustained across all efficacy endpoints: nocturnal urinary frequency, nocturnal urinary volume, hours of undisturbed sleep, nocturnal polyuria index, initial nocturnal urinary volume, and daily urinary frequency
- Improvements were measured at 1, 4, 12, 24, and 52 weeks
- BNP (brain natriuretic peptide) level rose over the year, but cardiothoracic ratio on chest X-ray was unchanged
- Body composition was not significantly affected
- Long-term administration deemed effective and safe in older men
Kurose, Hirofumi; Ueda, Kosuke; Chikui, Katsuaki; Uemura, Keiichiro; Nishihara, Kiyoaki; Nakiri, Makoto; Suekane, Shigetaka; Igawa, Tsukasa ·
RPEP-08622 · 2024In a survey of 133 adults with type 1 diabetes, 28% reported unmet treatment needs, primarily in glycemic control, management-related fatigue, and weight management. An overwhelming 94% indicated willingness to use adjunctive therapies alongside insulin. When presented with masked drug profiles, 94% preferred liraglutide's risk-benefit profile (1.8 mg, then 0.6 mg) over placebo. Preferred administration routes were daily tablets (66%) and weekly injections (32%). Semi-structured interviews with 20 participants confirmed and extended these findings.
Lamaro, Bella D; Greenfield, Jerry R; Snaith, Jennifer R ·
RPEP-08632 · 2024This systematic review examined preclinical studies on two bee venom peptides — melittin and apamin — when conjugated with other cancer drugs or loaded into novel delivery systems. Melittin-based conjugates, including PEGylated versions, showed improved tumor-targeting ability and reduced toxicity across multiple cancer models. Apamin-conjugated formulations enhanced the effectiveness of established anti-cancer drugs while reducing off-target side effects.
The review found that these peptide conjugates address two major problems in cancer treatment: drug resistance and collateral damage to healthy tissue. By using melittin or apamin as targeting or delivery vehicles, researchers were able to concentrate anti-cancer agents at tumor sites more effectively than the drugs alone.
Laurindo, Lucas Fornari; de Lima, Enzo Pereira; Laurindo, Lívia Fornari; Rodrigues, Victória Dogani; Chagas, Eduardo Federighi Baisi; de Alvares Goulart, Ricardo; Araújo, Adriano Cressoni; Guiguer, Elen Landgraf; Pomini, Karina Torres; Rici, Rose Eli Grassi; Maria, Durvanei Augusto; Direito, Rosa; Barbalho, Sandra Maria · Systematic Review
RPEP-08637 · 2024Survodutide produced dose-dependent weight loss across all four dose groups over 46 weeks. Mean body weight changes from baseline were: -6.2% (0.6 mg), -12.5% (2.4 mg), -13.2% (3.6 mg), -14.9% (4.8 mg), compared to -2.8% with placebo.
Adverse events occurred in 91% of survodutide recipients versus 75% of placebo recipients. Gastrointestinal side effects were the most common, affecting 75% of survodutide users compared to 42% on placebo. Despite this, all doses were considered tolerable. Of the 386 treated participants, 60.4% completed the full 46-week treatment period, with similar completion rates between survodutide (61%) and placebo (60%).
le Roux, Carel W; Steen, Oren; Lucas, Kathryn J; Startseva, Elena; Unseld, Anna; Hennige, Anita M ·