RPEP-07839 · 2024The peptide nanofiber (NF-Dox) achieved complete internalization into TNBC cells (MDA-MB 231) within 1 hour, primarily through a translocation mechanism mediated by gH625. The antiproliferative effect of NF-Dox carrying 7.5 µM doxorubicin was equivalent to 50 µM free doxorubicin — a ~6.7-fold dose reduction. The empty carrier (NF) showed no toxicity to either healthy keratinocytes (HaCaT) or TNBC cells. The nanofiber was 250 nm long, 10 nm in diameter, and stable across varying dilution, ionic strength, and pH conditions.
The on-demand drug release was achieved through an MMP-9-cleavable linker, ensuring doxorubicin was only released in the tumor microenvironment where MMP-9 is overexpressed.
Bellavita, Rosa; Piccolo, Marialuisa; Leone, Linda; Ferraro, Maria Grazia; Dardano, Principia; De Stefano, Luca; Nastri, Flavia; Irace, Carlo; Falanga, Annarita; Galdiero, Stefania ·
RPEP-07840 · 2024Short bombesin peptide was incorporated into various domains of arachnid and plant toxin scaffolds containing inhibitory cystine knots via solid-phase peptide synthesis. Placing bombesin between the first and second cysteine residues in arachnid toxins yielded the best results — increased in vitro stability and bioavailability as assessed by HPLC, maintained receptor binding in cell cultures expressing bombesin receptors, and low cytotoxicity confirmed by fluorescence microscopy.
Beloborodov, Evgenii; Iurova, Elena; Sugak, Dmitrii; Rastorgueva, Eugenia; Pogodina, Evgeniya; Fomin, Aleksandr; Viktorov, Denis; Slesarev, Sergei; Saenko, Yury ·
RPEP-07843 · 2024Untargeted metabolomics profiling of plasma from 20 T2DM patients pre- and post-liraglutide treatment identified 93 endogenous metabolites that were significantly altered — 49 upregulated and 44 downregulated.
Key affected metabolic pathways included:
- Pentose and glucuronate interconversion — a pathway important for eliminating toxic substances from the body
- Alanine, aspartate, and glutamate metabolism — amino acid pathways that may improve immune cell function
- Metabolites involved in defense against oxidative stress were also induced by liraglutide
These metabolic alterations may partially explain liraglutide's cardiovascular and anti-inflammatory benefits beyond its primary glucose-lowering effect.
Benabdelkamel, Hicham; Sebaa, Rajaa; AlMalki, Reem H; Masood, Afshan; Alfadda, Assim A; Abdel Rahman, Anas M ·
RPEP-07844 · 2024GTN treatment (5 mg/kg) tended to increase CGRP concentration in trigeminal ganglia after single administration, but repetitive GTN treatment decreased CGRP levels, suggesting store depletion. No significant difference in CGRP concentration was observed between fremanezumab-treated and control antibody-treated animals, indicating GTN increases CGRP production independently of antibody treatment.
Behaviorally, GTN-treated rats spent less time at a sugar solution source and consumed less, indicating suppressed activity and increased facial sensitivity. Under mechanical barrier conditions, fremanezumab partly compensated for GTN's depressive effects, with treated animals being more active. The findings suggest that if CGRP and NO share the same pathway in sensitizing trigeminal afferents, NO acts downstream of CGRP.
Benedicter, Nicola; Vogler, Birgit; Kuhn, Annette; Schramm, Jana; Mackenzie, Kimberly D; Stratton, Jennifer; Dux, Mária; Messlinger, Karl ·
RPEP-07845 · 2024This clinical practice review describes the nursing roles in administering peptide receptor radionuclide therapy (PRRT) using 177Lu-DOTATATE for patients with somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs). The peptide-based therapy targets somatostatin receptors expressed on neuroendocrine tumor cells, delivering targeted radiation directly to tumors. Oncology nurses play critical roles in patient assessment, education, direct care during infusion, monitoring for adverse effects, and providing emotional support throughout treatment.
Bennett, Bonita; Gardner, Linda; Ryan, Pamela · Review
RPEP-07849 · 2024ACE (angiotensin-converting enzyme) has a second, nonclassical function beyond making angiotensin II: when immune cells like macrophages and neutrophils increase their ACE expression, it dramatically boosts their ability to fight tumors, infections, atherosclerosis, and Alzheimer's disease. Genetically modified 'ACE 10/10' mice with increased macrophage ACE were much more resistant to all these conditions. This immune-boosting effect works through an unknown peptide (not angiotensin II) that shifts macrophage metabolism toward increased mitochondrial fat burning and ATP production. Conversely, ACE inhibitor drugs reduce neutrophil bacteria-killing ability in both mice and humans.
Bernstein, Kenneth E; Cao, DuoYao; Shibata, Tomohiro; Saito, Suguru; Bernstein, Ellen A; Nishi, Erika; Yamashita, Michifumi; Tourtellotte, Warren G; Zhao, Tuantuan V; Khan, Zakir ·
RPEP-07851 · 2024In 8 participants with moderate hepatic impairment (Child-Pugh 7-9) versus 8 matched healthy controls, a single 10-mg intranasal zavegepant dose showed approximately 2-fold increase in total AUC0-inf (GLSM ratio 193%, 90% CI: 112-333) and 16% increase in Cmax (GLSM ratio 116%, 90% CI: 69-195). Unbound zavegepant showed similar patterns (~2.3-fold AUC increase, 39% Cmax increase). The unbound fraction was similar between groups (0.13 vs 0.11).
Only one treatment-emergent adverse event (mild headache) occurred, in a healthy participant. These changes were not considered clinically meaningful, supporting no dose adjustment for mild or moderate hepatic impairment.
Bhardwaj, Rajinder; Donohue, Mary K; Madonia, Jennifer; Morris, Beth; Marbury, Thomas C; Matschke, Kyle T; Croop, Robert; Bertz, Richard; Liu, Jing ·
RPEP-07854 · 2024The common food additive λ-carrageenan significantly reduced both proglucagon gene expression and GLP-1 peptide secretion in human intestinal L-cells at a concentration of just 1 µg/ml. This inhibition was observed at 10 minutes, 1 hour, and 24 hours of exposure. The effect was confirmed in mouse L-cells as well.
Furthermore, when intestinal epithelial cells were exposed to spent media from carrageenan-treated L-cells, they showed decreased expression of the GLUT-2 glucose transporter, suggesting secondary downstream effects on glucose metabolism beyond direct GLP-1 suppression.
Bhattacharyya, Sumit; Borthakur, Alip; Tobacman, Joanne K ·
RPEP-07859 · 2024In streptozotocin/high-fat-diet diabetic rats, 21 days of liraglutide treatment (200 μg/kg/day subcutaneous) produced multiple renoprotective effects: decreased serum biomarkers of diabetic nephropathy, reduced histological abnormalities in kidney tissues, and decreased protein expression of three key molecules in the lysophosphatidic acid (LPA) axis — PCNA (a cell proliferation marker), autotaxin (the enzyme that produces LPA), and KLF5 (the transcription factor that regulates autotaxin expression).
The downregulation of all three components suggests liraglutide works upstream through KLF5 to suppress the entire LPA signaling cascade that drives kidney fibrosis and damage in diabetes.
Bin Dayel, Anfal F; Alrasheed, Nouf M; Alonazi, Asma S; Alamin, Maha A; Al-Mutairi, Nawal M; Alateeq, Raghad A ·
RPEP-07864 · 2024Over 26 weeks, dulaglutide reduced eGFR by 5.8 mL/min/1.73 m² versus only 0.1 in the placebo group (p=0.016). This decrease was concentrated in participants who started with glomerular hyperfiltration — a paradoxically high filtration rate that signals early kidney damage.
Critically, the prevalence of both glomerular hyperfiltration and proteinuria (protein in the urine) decreased with dulaglutide but increased with placebo (p=0.014 and p=0.004, respectively). In the context of diabetic kidney disease, a reduction in hyperfiltration is considered protective — it means the kidneys are working under less stress, potentially slowing progression to irreversible damage.
Bjornstad, Petter; Arslanian, Silva A; Hannon, Tamara S; Zeitler, Philip S; Francis, Jennie L; Curtis, Alexandra M; Turfanda, Ibrahim; Cox, David A ·
RPEP-07869 · 2024Survodutide produced dose-dependent HbA1c reductions up to -1.71% (DG3, 1.8 mg weekly) and weight loss up to -8.7% (DG6, 1.8 mg twice weekly) over 16 weeks. At lower doses, survodutide matched semaglutide for HbA1c reduction (-1.46% vs. -1.47%). At higher doses, survodutide produced significantly greater weight loss than semaglutide (-8.7% vs. -5.3%). Gastrointestinal adverse events were the most common side effects, occurring in 77.8% of survodutide-treated participants versus 52% with semaglutide and 52.5% with placebo. A clear dose-response relationship was observed for both efficacy and adverse events.
Blüher, Matthias; Rosenstock, Julio; Hoefler, Josef; Manuel, Raymond; Hennige, Anita M ·
RPEP-07871 · 2024PRRT using lutetium-177-labeled somatostatin analogs has become the dominant form of peptide-targeted radiation therapy for neuroendocrine tumors, replacing earlier yttrium-90-based approaches. The treatment achieves significant tumor control and symptom relief in patients with somatostatin receptor-positive neuroendocrine tumors.
However, as with other systemic therapies, treatment responses are relatively short-lived. The field is now focused on developing new peptides and treatment strategies, with a critical emphasis on individualizing therapy through patient-specific dosimetry — calculating radiation doses to both tumors and healthy organs — and understanding tissue-level radiosensitivity.
Bodei, Lisa; Jayaprakasam, Vetri Sudar; Ying Wong, Bernadette Zhi; Aparici, Carina Mari ·
RPEP-07875 · 2024Co-administration of atogepant with quinidine gluconate resulted in no significant change in atogepant's peak plasma concentration. The overall systemic exposure (AUC) of atogepant increased by approximately 25%, but this increase was not considered clinically relevant.
Atogepant did not alter quinidine's mean plasma concentration at steady state. The incidence of treatment-emergent adverse events was highest when quinidine gluconate was given alone (42.4%), primarily driven by QT prolongation. Most adverse events were mild and resolved within 1-2 days. The modest exposure increase was attributed to quinidine's inhibition of CYP2D6 and P-gp, both minor contributors to atogepant clearance.
Boinpally, Ramesh; Borbridge, Lisa; Wangsadipura, Veronica ·
RPEP-07880 · 2024The antimicrobial peptide LL-37 and RNA from neutrophil extracellular traps (NETs) form a composite 'damage signal' (DAMP) that triggers a self-amplifying cycle of inflammation. This naRNA-LL37 complex stimulates fresh neutrophils to release more NETs via a TLR8–NLRP3 inflammasome pathway, and causes skin cells (keratinocytes) to express psoriasis-related genes (IL17, IL36) through NOD2-RIPK signaling.
Critically, the naRNA-LL37 DAMP is pre-stored in resting neutrophil granules — meaning it's ready to go before any infection occurs. In live mice, it drove temporary skin inflammation that was dramatically reduced when RNA-sensing was genetically eliminated. Under normal conditions, the signal is self-limiting, but when NET release is dysregulated (as in psoriasis), it creates a runaway inflammatory loop.
Bork, Francesca; Greve, Carsten L; Youn, Christine; Chen, Sirui; N C Leal, Vinicius; Wang, Yu; Fischer, Berenice; Nasri, Masoud; Focken, Jule; Scheurer, Jasmin; Engels, Pujan; Dubbelaar, Marissa; Hipp, Katharina; Zalat, Baher; Szolek, Andras; Wu, Meng-Jen; Schittek, Birgit; Bugl, Stefanie; Kufer, Thomas A; Löffler, Markus W; Chamaillard, Mathias; Skokowa, Julia; Kramer, Daniela; Archer, Nathan K; Weber, Alexander N R · Basic Research
RPEP-07889 · 2024Exenatide monotherapy reduced lipid accumulation in steatotic HepG2 cells by 25%. Combined glucagon and exenatide treatment significantly reduced markers of oxidative stress: reactive oxygen species (ROS) decreased by 24% and malondialdehyde (MDA, a lipid peroxidation marker) by 21%.
The oxidative stress reduction was associated with increased expression of two antioxidant enzymes — superoxide dismutase (SOD) and glutathione peroxidase (GPx) — but not catalase (Cat). This suggests dual GLP-1 and glucagon receptor activation enhances the cell's antioxidant defense capacity.
Bołdys, Aleksandra; Bułdak, Łukasz; Skudrzyk, Estera; Machnik, Grzegorz; Okopień, Bogusław ·
RPEP-07890 · 2024Peptide-receptor radionuclide imaging with 68Ga-DOTATOC identified increased somatostatin receptor expression in a suprasellar hemangioblastoma in a VHL patient. The same scan revealed multiple pancreatic neuroendocrine tumors and bilateral pheochromocytomas.
After one year of treatment with lanreotide (a somatostatin analog), repeat 68Ga-DOTATOC imaging showed decreased radiotracer uptake by the hemangioblastoma, consistent with a metabolic response. This is significant because no systemic therapy has previously shown a response in VHL-associated hemangioblastomas, and somatostatin receptor expression in these tumors had only recently been reported in the literature.
Brabo, Eloá Pereira; de Almeida, Sergio Altino; Rafful, Patrícia Piazza; Rosado-de-Castro, Paulo Henrique; Vieira Neto, Leonardo ·
RPEP-07892 · 2024A 72-year-old male developed bilateral, incongruent central scotomata (blind spots) under scotopic (low-light) conditions 17 days after initiating 3.0 mg daily oral semaglutide. The scotoma started in the right eye and expanded over several days before appearing in the left eye. Symptoms were only present in dim light and absent in daylight or artificial lighting. All symptoms completely resolved within 2 days of medication discontinuation. Comprehensive ophthalmologic evaluation including macular OCT, fundus photography, fundus autofluorescence, and Humphrey visual field testing revealed no structural abnormalities.
Bracha, Peter; Johnson, William; Chu, Sabrina; Davison, James ·
RPEP-07893 · 2024The patient experienced only mild and self-limiting symptoms following intentional semaglutide overdose. The specific overdose amount was not detailed in the abstract, but the clinical course was benign, requiring no specific antidote or intensive medical intervention.
This finding is notable because semaglutide overdose data is extremely limited in the medical literature, yet the drug is now one of the most widely prescribed medications globally. The case contributes to the understanding of semaglutide's safety margin — the gap between therapeutic and dangerous doses — which appears to be substantial.
Branch, Matthew R; Amador, Isabella E; Tardif, Irina; Patel, Kruti K; Lewis, Daniel A ·
RPEP-07897 · 2024Researchers developed a targeted LC-MS/MS method to analyze peptide markers in dried blood spot (DBS) samples that can estimate when a blood sample was collected. They tracked peptide changes across 10 volunteers over 3 months at three storage temperatures (room temperature, 4 degrees C, and -20 degrees C).
Two peptide area ratios — calculated from peptides originating from the same parent protein — significantly increased after 28 days of room temperature storage. These ratios serve as potential time-since-collection markers, which could verify that athletes actually collected their DBS samples when they claimed to during remote self-sampling for anti-doping purposes.
Brockbals, Lana; Thomas, Andreas; Schneider, Tom D; Kraemer, Thomas; Steuer, Andrea E; Thevis, Mario · Original Research
RPEP-07902 · 2024Of 472 patients treated with anti-CGRP/R monoclonal antibodies, 136 (28.8%) discontinued after an average of 9.0 months. Ineffectiveness was the primary reason (70.6%), followed by loss to follow-up (13.1%) and adverse events (7.3%). Most (77.9%) discontinued within the first year. Response rates (≥50% reduction in monthly headache days) were 30.5% at 3 months, 34.6% at 6 months, and 40.0% at 12 months — but only 16.9% were responding in their last month before discontinuation. After stopping, 48.5% started new treatment, with 67.6% of those switching to a different anti-CGRP antibody.
Burgalassi, Andrea; Romozzi, Marina; Vigani, Giulia; De Icco, Roberto; Raffaelli, Bianca; Boccalini, Alberto; De Cesaris, Francesco; Calabresi, Paolo; Geppetti, Pierangelo; Chiarugi, Alberto; Iannone, Luigi Francesco ·
RPEP-07903 · 2024Among 3,193 eligible patients, fremanezumab initiation was associated with significant reductions in: acute medication claims (0.97 to 0.86 PPPM, p<0.001), preventive medication claims excluding fremanezumab (0.94 to 0.81 PPPM, p<0.001), outpatient visits, neurologist visits, ER visits, and other outpatient services (all p<0.001). Total migraine-related healthcare costs decreased from $541 to $490 PPPM (p=0.003). Adherence was good with mean proportion of days covered of 0.71 and persistence duration of 160.3 days at 6 months.
Buse, Dawn C; Krasenbaum, Lynda J; Seminerio, Michael J; Packnett, Elizabeth R; Carr, Karen; Ortega, Mario; Driessen, Maurice T ·
RPEP-07910 · 2024Three months of liraglutide treatment in obese patients shifted their macrophages from the inflammatory M1 type toward the anti-inflammatory M2 type. This phenotype switch was accompanied by reduced TNFα release (a key inflammatory cytokine) and decreased oxidative stress markers (reactive oxygen species and malondialdehyde).
This is one of the first in vivo human studies to show that GLP-1 analogs directly alter immune cell behavior — not just in a lab dish but in actual patients. The shift toward M2 macrophages could help explain why GLP-1 drugs reduce cardiovascular events: M1 macrophages drive atherosclerotic plaque formation and instability, while M2 macrophages promote tissue repair.
Bułdak, Łukasz; Bołdys, Aleksandra; Skudrzyk, Estera; Machnik, Grzegorz; Okopień, Bogusław · Pilot Clinical Study
RPEP-07914 · 2024This review catalogues the antioxidant properties of collagen peptides derived from marine sources including fish (skin, bones, scales, fins, cartilage), jellyfish, mollusks, crustaceans, and sponges. The authors found that specific amino acid sequences in marine collagen hydrolysates demonstrate significant antioxidant activity, and that the extraction method used to break down collagen into peptides affects which antioxidant properties are preserved. Marine collagen peptides from both vertebrate and invertebrate sources showed potential as natural antioxidant nutraceuticals.
Cadar, Emin; Pesterau, Ana-Maria; Prasacu, Irina; Ionescu, Ana-Maria; Pascale, Carolina; Dragan, Ana-Maria Laura; Sirbu, Rodica; Tomescu, Cezar Laurentiu ·
RPEP-07915 · 2024Across 12 randomized controlled trials with 11,758 patients, tirzepatide significantly reduced BMI (mean difference -1.71, 95% CI -2.46 to -0.95), waist circumference, and body weight compared to GLP-1 receptor agonists, placebo, and insulin. Tirzepatide outperformed existing GLP-1 drugs for weight loss. Gastrointestinal side effects were the primary safety concern but overall safety was considered high.
Cai, Wenting; Zhang, Ruobin; Yao, Yao; Wu, Qiuhui; Zhang, Jinping ·
RPEP-07917 · 2024The negatively charged peptide hydrogel 3E-OX demonstrated physicochemical properties closely resembling native vitreous humor, including optimal light transmittance, refractive index, molecular permeability, and viscoelasticity. In contrast, the positively charged variant (3K-OX) was less suitable.
Animal studies in rabbits confirmed the safety and biocompatibility of 3E-OX as a vitreous substitute. The researchers also introduced optical coherence tomography (OCT) for retinal microvascular detection in non-pigmented rabbits as a novel method to evaluate intraocular tamponade materials, providing more detailed assessment of retinal health after vitreous replacement.
Cai, Yuting; Xiang, Yatong; Dong, Huilei; Huang, Wenjing; Liu, Yan; Zhao, Chenguang; Yuan, Dan; Li, Yun; Shi, Junfeng ·
RPEP-07918 · 2024Desmopressin, a synthetic peptide analog of vasopressin, self-assembles with the polymer sodium polystyrene sulfonate (NaPSS) to form hybrid fibrillar nanostructures enriched in β-turn and β-sheet domains. When tested against breast cancer cell lines, these peptide-polymer complexes were well-tolerated by non-metastatic MCF-7 cells but showed inhibitory effects against the highly metastatic MDA-MB-231 cells, suggesting selective anticancer activity.
Caliari, Ana B; Bicev, Renata N; da Silva, Caroline C; de Souza, Sinval E G; da Silva, Marta G; Souza, Louise E A; de Mello, Lucas R; Hamley, Ian W; Motta, Guacyara; Degrouard, Jéril; Tresset, Guillaume; Quaresma, Alexandre J C; Nakaie, Clovis R; da Silva, Emerson R ·
RPEP-07924 · 2024Using transgenic mice carrying the human DEFA1A3 gene, researchers demonstrated that alpha-defensin 1-3 expression and antimicrobial activity against uropathogenic E. coli (UPEC) are directly dependent on gene copy number — more copies mean stronger defense.
Alpha-defensin 1-3 was expressed by both kidney neutrophils and collecting duct intercalated cells, establishing two sources of this antimicrobial peptide in the urinary tract. The defensins showed cooperative effects with other antimicrobial peptides, potentiating their bacteria-killing activity. Higher gene dosage also modulated pro-inflammatory innate immune responses, demonstrating that DEFA1A3 has both direct antimicrobial and immunomodulatory roles during UTI.
Canas, Jorge J; Arregui, Samuel W; Zhang, Shaobo; Knox, Taylor; Calvert, Christi; Saxena, Vijay; Schwaderer, Andrew L; Hains, David S ·
RPEP-07933 · 2024Across 2,249 consecutive clinical copper-64 DOTATATE PET/CT scans in 1,290 neuroendocrine tumor patients:
- **Most common indication**: Monitoring without clinical progression (31.3% of scans)
- **Image results**: No disease in 29.7%, stable disease in 25.9%, progression in 20.5%
- **PET-only progression**: In 99 of 461 cases with progression (21.5%), disease worsening was detected by PET but not by CT
- **Initial staging** accounted for 9.8% and **PRRT selection** for 4.2% of scans
- **16.5% of scans** were for indications not even defined in current appropriate use criteria
The high detection rate of progression in the monitoring group — particularly PET-only progression — supports upgrading this indication from "may be appropriate" to "appropriate" in guidelines.
Carlsen, Esben Andreas; Loft, Mathias; Johnbeck, Camilla Bardram; Knigge, Ulrich; Langer, Seppo W; Mortensen, Jann; Enevoldsen, Lotte; Oturai, Peter; Kjaer, Andreas ·
RPEP-07937 · 2024Three months of CGRP monoclonal antibody therapy in migraine patients preserved cerebral autoregulation (CA) and cerebrovascular reactivity (CVR) in both the middle and posterior cerebral arteries (all p>0.38). Blood flow velocity and blood pressure were also unaffected overall. However, patients who responded clinically (>50% migraine reduction) showed a small but significant reduction in cerebral blood flow velocity in MCA (6.0 cm/s, p=0.007) and PCA (8.9 cm/s, p=0.04).
Carter, Sarah C; Cucchiara, Brett; Reehal, Navpreet; Hamilton, Katherine; Kaiser, Eric A; Favilla, Christopher G ·
RPEP-07941 · 2024GFAP-IL6 transgenic mice (with astrocyte-targeted IL-6 production) showed significantly increased transcripts and protein levels of both PACAP and VIP, plus their receptors PAC1, VPAC1, and VPAC2, in both cerebrum and cerebellum compared to wild-type littermates. This was accompanied by robust activation of JAK/STAT3, NF-κB, and ERK1/2MAPK signaling pathways. Blocking IL-6 trans-signaling (using sgp130Fc co-expression) reduced VIP expression and attenuated STAT3 and NF-κB activation, but failed to rescue PACAP levels, receptor expression, or ERK1/2MAPK phosphorylation — indicating PACAP induction involves trans-signaling-independent mechanisms.
Castorina, Alessandro; Scheller, Jurgen; Keay, Kevin A; Marzagalli, Rubina; Rose-John, Stefan; Campbell, Iain L ·
RPEP-07942 · 2024A new adjuvant combination — the TLR9 agonist K3 CpG plus the STING agonist c-di-AMP — produced T cell responses against tumor neopeptides that were 10 times stronger than poly-IC (the leading adjuvant currently in clinical neoantigen vaccine trials). When combined with synthetic long peptides (20-mers) from melanoma and lung mesothelioma neoantigens, this formulation induced potent antigen-specific T cell immunity in mice.
In a melanoma mouse model, the vaccine controlled tumor growth and improved survival, and it synergized with anti-PD-1 checkpoint immunotherapy — meaning the combination worked better than either approach alone.
Castro Eiro, Melisa D; Hioki, Kou; Li, Ling; Wilmsen, Merel E P; Kiernan, Caoimhe H; Brouwers-Haspels, Inge; van Meurs, Marjan; Zhao, Manzhi; de Wit, Harm; Grashof, Dwin G B; van de Werken, Harmen J G; Mueller, Yvonne M; Schliehe, Christopher; Temizoz, Burcu; Kobiyama, Kouji; Ishii, Ken J; Katsikis, Peter D · Animal Study
RPEP-07943 · 2024Fasting increased and refeeding decreased AMPK phosphorylation (AMPKThr172) in the central nucleus of the amygdala (CeA), confirming AMPK responds to nutritional status in this brain region.
Intra-CeA ghrelin injection increased both food intake and AMPKThr172 phosphorylation, establishing ghrelin-AMPK signaling as a feeding-promoting pathway in the amygdala. Glucose injection into the CeA decreased feeding, while 2-deoxy-D-glucose (a glucoprivation inducer) increased food intake and blood glucose.
Chronic intra-CeA injection of Melanotan II (MTII) over 7 days reduced body mass and food intake with a slight decrease in AMPKThr172, demonstrating that melanocortin peptide signaling opposes the ghrelin-AMPK feeding axis in this brain region.
Castro, Gisele; Mendes, Natália Ferreira; Weissmann, Laís; Quaresma, Paula Gabriele Fernandes; Saad, Mario Jose Abdalla; Prada, Patricia Oliveira ·
RPEP-07944 · 2024In a study of 308 adults, three of four urinary antimicrobial peptides (HNP 1-3, HD-5, and LL-37) showed no significant differences between adults aged 65+ and those under 65. However, human beta-defensin-2 (hBD-2) was significantly lower in older adults of both sexes (p < .001 for males, p = .004 for females). Additionally, urine leukocyte esterase was associated with increased HNP 1-3 and HD-5 levels, hematuria with increased hBD-2, and contaminated urine cultures with increased HNP 1-3 and hBD-2.
Caterino, Jeffrey M; Stephens, Julie A; Wexler, Randell; Camargo, Carlos A; Hunold, Katherine M; Wei, Lai; Hains, David; Southerland, Lauren T; Bischof, Jason J; Schwaderer, Andrew ·
RPEP-07958 · 2024While GLP-1 receptor agonists do increase residual gastric contents (19-56% of users vs. 5-20% of non-users in 7 of 8 comparative studies), the available evidence does not show a significant increase in actual aspiration or regurgitation events. In three retrospective studies that specifically tracked aspiration events, one found nearly identical rates (4.8 vs. 4.6 per 10,000) and the other two found only one aspiration event in GLP-1 users versus none in controls.
Critically, the review found that nearly all studies had significant confounding factors — patients on GLP-1 drugs typically had diabetes, obesity, and other conditions that independently delay gastric emptying. The authors conclude that current societal guidelines recommending withholding GLP-1 drugs before surgery may not be well-supported by the available data.
Chang, Marvin G; Ripoll, Juan G; Lopez, Ernesto; Krishnan, Kumar; Bittner, Edward A · Scoping Review
RPEP-07964 · 2024Migraine showed strong genetic correlation with non-immune GI disorders: IBS (rg = 0.37, p = 10⁻²¹), GERD, PUD, FD, and DD. No correlation was found with IBD. However, local genetic sharing at the CALCA/CALCB genes (encoding CGRP) was concordant and significant for diverticular disease, IBD, and ulcerative colitis, suggesting anti-CGRP therapies could benefit these conditions.
Mendelian randomization supported causal effects of some GI conditions on migraine — particularly diverticular disease (OR 1.90, p = 2.2 × 10⁻⁴) — but not of migraine on GI conditions. CNS-related genes were enriched in the genetic overlap of GERD, IBS, and PUD with migraine, supporting neurologic mechanisms.
Chasman, Daniel I; Guo, Yanjun; Chan, Andrew T; Rist, Pamela M; Staller, Kyle ·
RPEP-07965 · 2024This review summarizes the current understanding of diabetes insipidus — now proposed to be renamed 'vasopressin deficiency' (central form) and 'vasopressin resistance' (nephrogenic form) to avoid confusion with diabetes mellitus. The standard treatment for central diabetes insipidus is desmopressin, a synthetic analog of the peptide hormone vasopressin.
Importantly, the review highlights that desmopressin treatment doesn't always restore optimal quality of life. The authors suggest this may be because patients with neurohypophyseal dysfunction are also deficient in oxytocin, another peptide hormone secreted from the same brain region. A new diagnostic test using oxytocin stimulation could help identify these patients.
Chasseloup, Fanny; Tabarin, Antoine; Chanson, Philippe · Review
RPEP-07970 · 2024Micro-CT analysis showed that both low-dose (10 mg/kg/day) and high-dose (40 mg/kg/day) hydrolyzed egg yolk peptide (YPEP) improved bone mineral density and bone microstructure in ovariectomized rats. Three-point bending tests confirmed enhanced biomechanical strength.
Serum markers of bone formation (BALP, BGP, calcium, phosphorus) were significantly elevated in YPEP groups, while bone resorption markers (ALP, TRAP, CTX-I) were reduced in the low-dose group. At the molecular level, YPEP upregulated key proteins in the Wnt/β-catenin pathway (Wnt3a, β-catenin, LRP5, RUNX2, OPG) and increased the OPG/RANKL ratio — shifting the balance from bone breakdown toward bone formation. Gut microbiota changes (increased Lachnospiraceae_NK4A136_group, decreased Escherichia_Shigella) were observed but did not correlate with bone outcomes.
Chen, Chuanjing; Huang, Ludi; Chen, Yuanyuan; Jin, Jin; Xu, Ze; Liu, Fei; Li, Kelei; Sun, Yongye ·
RPEP-07974 · 2024The poly(2-oxazoline)-based nanovaccine platform self-assembled into uniform ~50 nm nanoparticles and could conjugate neoantigen peptides regardless of their physicochemical properties. This improved antigen accumulation and infiltration in lymph nodes, enhancing antigen presentation to immune cells.
When conjugated with three predicted neoantigen peptides from the MC38 colon tumor cell line, the nanovaccine induced robust CD8+ T cell responses in 100% of vaccinated mice and achieved superior tumor clearance compared to free (unconjugated) peptides.
Chen, Hongyu; Zhu, Zhenyi; Lv, Kuncheng; Qi, Yibo; Si, Xinghui; Ma, Sheng; Song, Wantong; Chen, Xuesi ·
RPEP-07977 · 2024A new somatostatin receptor-targeting radioactive peptide, [177Lu]Lu-LNC1010, showed higher tumor uptake, longer retention, and greater tumor growth inhibition than the standard [177Lu]Lu-DOTATATE in nasopharyngeal carcinoma (NPC) cell and mouse models. The enhanced performance comes from an Evans blue-binding moiety and PEG linker added to the DOTATATE backbone, which extends circulation time. In a proof-of-concept human case, PRRT with LNC1010 achieved favorable therapeutic results with negligible side effects in a metastatic NPC patient.
Chen, Jianhao; Pang, Yizhen; Liao, Xiyi; Zhou, Yangfan; Luo, Qicong; Wu, Hua; Zuo, Changjing; Zhang, Jingjing; Lin, Qin; Chen, Xiaoyuan; Zhao, Liang; Chen, Haojun ·
RPEP-07980 · 2024Three months of liraglutide treatment significantly reduced albuminuria in type 2 diabetes patients with both microalbuminuria and macroalbuminuria, with greater reductions in patients who had worse kidney function at baseline. Liraglutide also decreased inflammatory markers (TNF-α, IL-6, MCP-1) and oxidative stress markers (MDA) while increasing antioxidant enzymes (SOD, glutathione peroxidase) across all patient groups. The degree of albuminuria reduction correlated with improvements in oxidative stress and inflammation, suggesting these mechanisms underlie liraglutide's kidney-protective effects. Blood sugar, HbA1c, and BMI also improved in all groups.
Chen, Shumei; He, Meiqing; Qin, Yufan; Tian, Jing; Liang, Zerong; Li, Ying; Wang, Peihua; Zhang, Youzhi; Zhou, Cui; Xiao, Juan ·
RPEP-07986 · 2024GLP-1 receptor-positive neurons in the lateral septum (LSGLP-1R) were robustly activated by liraglutide. Chemogenetic activation of these neurons dramatically suppressed feeding. Critically, targeted knockdown of GLP-1 receptors in the lateral septum — but not in the hypothalamus — substantially attenuated liraglutide's ability to inhibit feeding and lower body weight. The activity of LSGLP-1R neurons rapidly decreased during naturalistic feeding episodes, and synaptic inactivation of these neurons diminished liraglutide's anorexic effects.
Chen, Zijun; Deng, Xiaofei; Shi, Cuijie; Jing, Haiyang; Tian, Yu; Zhong, Jiafeng; Chen, Gaowei; Xu, Yunlong; Luo, Yixiao; Zhu, Yingjie ·
RPEP-07987 · 2024The GLP-1 receptor agonist exenatide significantly outperformed insulin in promoting bone formation and implant integration in diabetic rats. Exenatide extensively promoted peri-implant osseointegration through the LRP5/6/GSK-3β/β-catenin Wnt signaling pathway, while also inhibiting fat formation (via BMPR1A suppression) and reducing inflammation (via β-TrCP). Both in vivo micro-CT analysis and in vitro bone marrow stromal cell experiments confirmed exenatide's superior osteogenic effects compared to insulin.
Chen, Zijun; Wang, Yuxi; Zhang, Guanhua; Zheng, Jian; Tian, Lei; Song, Yingliang; Liu, Xiangdong ·
RPEP-08014 · 2024Tirzepatide is a novel peptide that selectively binds and activates both the GIP and GLP-1 receptors. The review consolidates evidence from multiple clinical trials showing:
- Tirzepatide produces superior blood sugar (HbA1c) reductions compared to GLP-1-only drugs
- It achieves greater weight loss than existing single-target treatments
- The dual GIP/GLP-1 mechanism provides complementary metabolic benefits
- It is already authorized in several countries for type 2 diabetes and obesity
The GIP component adds benefits beyond what GLP-1 activation alone can achieve, including enhanced insulin secretion and potentially different effects on fat metabolism and energy expenditure.
Ciardullo, Stefano; Morieri, Mario Luca; Daniele, Giuseppe; Fiorentino, Teresa Vanessa; Mezza, Teresa; Tricò, Domenico; Consoli, Agostino; Del Prato, Stefano; Giorgino, Francesco; Piro, Salvatore; Solini, Anna; Avogaro, Angelo ·
RPEP-08019 · 2024Transglutaminase type 2 (TGase) enzymatic cross-linking successfully increased the stiffness and resilience of self-assembling peptide (SAP) hydrogels without reducing their maximum stress-at-failure. The enzyme creates isopeptide bonds between peptide chains, strengthening the material while maintaining its fibrous nanostructure that mimics natural tissue.
Critically, the cross-linking process did not harm human neural stem cells (hNSCs) seeded within the hydrogel — cell viability and differentiation capacity were preserved, indicating that this strengthening technique could safely be performed in situ during biomedical applications.
Ciulla, Maria Gessica; Marchini, Amanda; Gazzola, Jacopo; Forouharshad, Mahdi; Pugliese, Raffaele; Gelain, Fabrizio ·
RPEP-08023 · 2024The HELP-hBD1 fusion biopolymer and its released active forms inhibited E. coli growth in redox environments. The fusion construct successfully produced the structurally complex human β-defensin 1, which is normally difficult to synthesize chemically due to its folding constraints.
Remarkably, 2D and 3D materials derived from the biopolymer showed strong cell adhesion-promoting activity, demonstrating dual functionality: antimicrobial protection and support for tissue growth. Engineered endoproteinase recognition sites allowed release of active hBD1 forms from the fusion carrier.
Colomina-Alfaro, Laura; Sist, Paola; D'Andrea, Paola; Urbani, Ranieri; Marchesan, Silvia; Stamboulis, Artemis; Bandiera, Antonella ·
RPEP-08025 · 2024A 47-year-old woman with type 2 diabetes and proliferative diabetic retinopathy (PDR) showed resolution of new blood vessel growth in her right eye and improved diabetic macular oedema within just 6 weeks of starting semaglutide therapy. Notably, this improvement occurred despite minimal changes in her blood sugar control, suggesting semaglutide may have a direct, independent effect on diabetic eye disease beyond its glucose-lowering properties.
Cool, Daniel; Coventon, James; Sharma, Abhishek · Case Report
RPEP-08027 · 2024Several families of host defense peptides (HDPs) have been identified in crocodilians:
- Cathelicidins — broad-spectrum antimicrobial peptides
- Beta-defensins — cysteine-rich antimicrobial/immune signaling peptides
- Hepcidins — iron-regulatory antimicrobial peptides
- Leucrocins — crocodilian-specific antimicrobial peptides
- Hemocidins — hemoglobin-derived antimicrobial fragments
- Omwaprins — wasp venom-like antimicrobial peptides found in crocodilians
These peptides collectively exhibit antimicrobial, anti-biofilm, antifungal, and anticancer activities. Crocodilian plasma has superior hemolytic capacity compared to other organisms, contributing to their exceptional wound-healing and infection resistance. The slow evolutionary rate of crocodilians means these defense mechanisms are highly conserved and well-optimized.
Cordero Gil, Trinidad de Los Ángeles; Moleón, María Soledad; Marelli, Belkis Ester; Siroski, Pablo Ariel ·
RPEP-08033 · 2024GPC3 is confirmed as an ideal cancer antigen for hepatocellular carcinoma (HCC) immunotherapy due to its high expression on tumor cells and limited expression in normal adult tissues. The GPC3 peptide vaccine developed by the authors has progressed from preclinical studies through first-in-human clinical trials.
In resectable HCC, the combination of immune checkpoint inhibitors and GPC3-targeted cancer vaccines appears promising as prophylactic adjuvant therapy to prevent recurrence. However, in advanced HCC, clinical trials across multiple modalities (peptide vaccines, antibody therapy, CAR-T/TCR-T cell therapy) have not demonstrated sufficient anti-tumor efficacy — a disconnect from the encouraging preclinical data that the field must address through reverse translation research.
Couzinet, Arnaud; Suzuki, Toshihiro; Nakatsura, Tetsuya ·
RPEP-08034 · 2024Anti-CGRP monoclonal antibodies (erenumab, fremanezumab, galcanezumab) significantly reduced headache days, migraine-without-aura days, acute medication use, and disability scores (MIDAS and HIT-6) over one year (p < 0.0001). However, these drugs did not reduce the frequency of migraine-with-aura attacks.
Interestingly, while aura episodes kept occurring at the same rate, the headache that normally follows the aura became less intense and shorter — and some patients experienced aura attacks with no headache at all.
The researchers propose that anti-CGRP antibodies work by blocking pain signaling in the trigeminal nerve pathway (a peripheral mechanism) but cannot stop cortical spreading depression — the wave of brain activity that causes the visual and sensory disturbances of aura.
Cresta, Elena; Bellotti, Alessia; Rinaldi, Giovanni; Corbelli, Ilenia; Sarchielli, Paola · Observational
RPEP-08036 · 2024Two phase 1 randomized studies in healthy adults demonstrated that rimegepant 75 mg orally disintegrating tablet (ODT) is bioequivalent to the 75 mg oral tablet:
- Sublingual ODT vs. oral tablet: AUC0-t ratio 97%, AUC0-inf ratio 97%, Cmax ratio 105% — all 90% CIs within the 80-125% bioequivalence range
- Supralingual ODT vs. oral tablet: AUC0-t ratio 98%, AUC0-inf ratio 98%, Cmax ratio 103% — all within bioequivalence criteria
Both delivery methods achieved equivalent drug exposure, confirming the ODT formulation provides consistent absorption regardless of whether it's placed under or on top of the tongue.
Croop, Robert; Bhardwaj, Rajinder; Anderson, Matt S; Matschke, Kyle T; Hould, Jennifer; Bertz, Richard; Liu, Jing; Lipton, Richard B ·