RPEP-09062 · 2024A 58-year-old woman with rapidly progressive, therapy-refractory neuroendocrine pancreatic tumor (grade G3) with extensive liver, bone, and lymph node metastases received three cycles of TANDEM peptide receptor radionuclide therapy (PRRT) using concurrently administered [177Lu]Lu-DOTA-LM3 and [225Ac]Ac-DOTA-LM3, a somatostatin receptor antagonist. The treatment produced complete regression of bone and lymph node metastases, significant reduction in liver metastases and hepatomegaly, and improvement in the primary pancreatic tumor. Partial remission was confirmed across multiple imaging modalities (PET/CT, contrast-enhanced CT, and abdominal MRI), with marked clinical improvement in pain, energy levels, and quality of life, enabling the patient to fully resume physical activity.
Perrone, Elisabetta; Ghai, Kriti; Eismant, Aleksandr; Andreassen, Mikkel; Langer, Seppo W; Knigge, Ulrich; Kjaer, Andreas; Baum, Richard P ·
RPEP-09067 · 2024Oxytocin (a peptide) and dopamine (a monoamine) are structurally completely different but share remarkably similar behavioral effects. Both are released during social interaction, sex, feeding, and massage, and both influence reward, motivation, and bonding. Critically, they affect each other's release and receptors, creating a bidirectional interaction network.
Deviations in both systems are associated with the same psychiatric conditions: anxiety, autism spectrum disorders, depression, ADHD, and schizophrenia. The review maps how these two chemically distinct signaling molecules converge on overlapping behavioral circuits, suggesting that many of oxytocin's effects on social behavior may be partially mediated through dopamine pathways and vice versa.
Petersson, Maria; Uvnäs-Moberg, Kerstin · Review
RPEP-09069 · 2024When semaglutide supply shortages hit Australia in 2022, prescriptions dropped 17% while dulaglutide prescriptions surged 53% as doctors switched patients to the available alternative. The shortages resulted in approximately 119,069 fewer semaglutide prescriptions than predicted over a 4-month period. When dulaglutide also experienced shortages shortly after, its prescriptions dropped 17% as well, leaving type 2 diabetes patients with limited GLP-1 agonist options.
Phakey, Sachin; Shen, Angeline · Retrospective Analysis
RPEP-09071 · 2024T7-conjugated cholesterol nanoparticle micelles loaded with temozolomide (TMZ) were efficiently taken up by neutrophils. T7 served a dual purpose: as a cell-penetrating peptide to enhance delivery into neutrophils, and as a transferrin-targeting peptide to direct delivery to tumor cells.
When T7/TMZ-conveyed neutrophils were injected intravenously into glioblastoma mouse models, they penetrated the blood-brain barrier and delivered the drug directly to tumor sites. The system demonstrated both efficient drug delivery and therapeutic effects against glioblastoma.
Piao, Chunxian; Lee, Jaeho; Kim, Gi Eun; Choe, Young Ho; Lee, Haerang; Hyun, Young-Min ·
RPEP-09074 · 2024Analysis of bovine milk using advanced proteomics revealed:
- Approximately 220 bovine proteins were quantified across breeds
- Cathelicidins (antimicrobial peptides) and annexins showed higher abundance in intensive-farming breeds compared to Podolica (traditional pasture breeds)
- Machine learning (LAP-MALDI MS with LDA) could distinguish Podolica milk from other breeds with 98.4% accuracy in the test set
- Antibiotic resistance proteins (beta-lactamases and tetracycline resistance proteins) were detected in milk from all breeds, with no significant breed-specific differences
- Metaproteomics revealed diverse microbial ecosystems in milk that varied with environmental factors
Piras, Cristian; De Fazio, Rosario; Di Francesco, Antonella; Oppedisano, Francesca; Spina, Anna Antonella; Cunsolo, Vincenzo; Roncada, Paola; Cramer, Rainer; Britti, Domenico ·
RPEP-09078 · 2024Using a standardized comparative analysis across cationic, anionic, and amphiphilic cell-penetrating peptides, the researchers demonstrated that intracellular delivery is fundamentally accompanied by irreparable plasma membrane damage as part of the uptake mechanism itself.
This creates an inescapable correlation: intracellular delivery efficiency scales directly with cell toxicity. The study also showed that CPPs are more efficient at delivering smaller peptides than large molecule cargo, further limiting their pharmaceutical utility.
The authors conclude that any delivery system based on conventional CPP designs or their underlying principles must accept low delivery yields, because toxicity inherently limits how much cargo can reach the cytoplasm. Novel peptide designs based on deeper understanding of uptake mechanisms are needed to overcome this barrier.
Polderdijk, Stéphanie G I; Limzerwala, Jazeel F; Spiess, Christoph ·
RPEP-09079 · 2024Anti-CGRP monoclonal antibodies reduced monthly migraine days, disability scores (MIDAS and HIT-6), and acute medication intake over a 24-month period in 120 resistant migraine patients. At 6 and 12 months, 61% and 57% of patients respectively achieved at least 50% reduction in monthly migraine days. Medication overuse at baseline was identified as a significant negative predictor of treatment response (OR 0.23, 95% CI 0.07–0.74, p = 0.014).
Pons-Fuster, E; Lozano-Caballero, O; Martín-Balbuena, S; Lucas-Ródenas, C; Mancebo-González, A; De Gorostiza-Frías, I; González-Ponce, C M · Retrospective Cohort
RPEP-09080 · 2024Tirzepatide did not just improve blood sugar control. It pushed many patients with type 2 diabetes all the way to normoglycemia, meaning their HbA1c dropped below 5.7%, the threshold where diabetes is no longer diagnosed.
The odds of achieving this were more than 16 times higher with tirzepatide versus control. This raises the question of whether tirzepatide could enable drug-induced diabetes remission, where blood sugar stays normal even after stopping medication.
Popovic, Djordje S; Patoulias, Dimitrios; Koufakis, Theocharis; Stavropoulos, Konstantinos; Karakasis, Paschalis; Ruža, Ieva; Papanas, Nikolaos; Rizzo, Manfredi; Doumas, Michael · Meta Analysis
RPEP-09081 · 2024Among people with type 2 diabetes, semaglutide was linked to a lower risk of medical encounters related to tobacco use disorder compared to other diabetes drug classes. The effect was strongest when comparing semaglutide to insulin. It was weakest compared to other GLP-1 receptor agonists, suggesting the effect may be partly a GLP-1 class effect rather than unique to semaglutide.
Semaglutide users also had fewer prescriptions for smoking cessation medications and less counseling for smoking. These patterns held regardless of whether patients were also obese.
Popovic, Djordje S; Patoulias, Dimitrios; Koufakis, Theocharis; Karakasis, Paschalis; Ruža, Ieva; Papanas, Nikolaos · Review/Commentary
RPEP-09082 · 2024Across all 9 trials, tirzepatide did not increase the risk of cancer overall or any specific cancer type. This held true regardless of what the comparison drug was.
However, the authors stress this is preliminary. The trials were short (36 to 72 weeks), which is not long enough to detect most drug-related cancer signals. Cancer takes years to develop, and these studies were designed to measure diabetes outcomes, not cancer risk.
Popovic, Djordje S; Patoulias, Dimitrios; Popovic, Lazar S; Karakasis, Paschalis; Papanas, Nikolaos; Mantzoros, Christos S · Meta Analysis
RPEP-09083 · 2024For acute migraine treatment, the three approved gepant drugs produced strong, statistically significant effects in women. The average drug effect for 2-hour pain freedom was 9.5% above placebo in women, with a number needed to treat of 11. In men, the average drug effect was only 2.8% above placebo and did not reach statistical significance. The number needed to treat in men was 36.
For migraine prevention, the picture was different. CGRP antibodies (erenumab, fremanezumab, galcanezumab, eptinezumab) and the oral preventive atogepant worked in both women and men for episodic migraine. In chronic migraine, the antibodies were similarly effective in both sexes.
Porreca, Frank; Navratilova, Edita; Hirman, Joe; van den Brink, Antoinette Maassen; Lipton, Richard B; Dodick, David W · Subgroup Analysis
RPEP-09084 · 2024Both exendin-4 and semaglutide improved outcomes when given right after brain injury in newborn mice. The drugs reduced the size of the damaged brain area, increased survival rates, and improved locomotor function in both short-term and long-term assessments.
The mechanism involved upregulation of the PI3K/AKT signaling pathway (a cell survival pathway) and increased cAMP levels (a molecule that helps cells communicate). The drugs also reduced inflammation after oxygen-glucose deprivation in brain cells.
Poupon-Bejuit, Laura; Geard, Amy; Millicheap, Nathan; Rocha-Ferreira, Eridan; Hagberg, Henrik; Thornton, Claire; Rahim, Ahad A · Animal Study
RPEP-09085 · 2024Semaglutide outperformed dulaglutide in both HbA1c reduction and weight loss, making it the most sought-after GLP-1 drug. Clinicians began prescribing Ozempic (semaglutide for diabetes) off-label for weight loss, even though Wegovy (semaglutide for weight) existed. This drove shortages.
Insurance companies responded by requiring prior authorizations proving a type 2 diabetes diagnosis before covering these drugs. The commentary notes that most insurance plans still do not cover GLP-1 drugs solely for weight management, pushing weight-loss demand onto the diabetes supply chain.
Powell, Jason; Taylor, James · Review/Commentary
RPEP-09086 · 2024Across 29 real-world Spanish studies, galcanezumab showed consistent reductions in monthly migraine days and monthly headache days. Disability scores (MIDAS) and headache impact scores (HIT-6) also improved.
12-month persistence ranged from 59.8% to 76.8%, meaning about 6 to 8 out of 10 patients stuck with treatment for a full year. Serious adverse events were rare. One study reported high patient satisfaction. No study included health-related quality of life data.
Pozo-Rosich, Patricia; García-Azorín, David; Díaz-Cerezo, Silvia; Fernández-Montoya, Julia; de Paz, Héctor David; Núñez, Mercedes · Systematic Review
RPEP-09087 · 2024PPAR agonists work by making cells more sensitive to insulin. Pioglitazone (a PPARγ agonist) and saroglitazar (a PPARα/γ agonist) are recommended by several medical groups for treating fatty liver in diabetes. Newer PPAR drugs like elafibranor and lanifibranor are also showing promise.
GLP-1 receptor agonists take a different approach. They produce significant weight loss and may directly reduce liver inflammation and fibrosis (scarring). The review notes that dual-agonists (like tirzepatide targeting GIP/GLP-1) and triple-agonists have produced even more impressive weight loss, which could further benefit the liver. However, direct evidence of liver benefit from these newer multi-agonists is still limited.
Pramanik, Subhodip; Pal, Partha; Ray, Sayantan · Review
RPEP-09088 · 2024Meta-analyses of long-term randomized controlled trials show DPP-4 inhibitors carry a small increased risk of acute pancreatitis, but GLP-1 receptor agonists and GLP-1/GIP co-agonists do not. GLP-1 receptor agonists and co-agonists are associated with higher rates of cholecystitis and cholelithiasis (gallbladder inflammation and gallstones). No incretin-based drug class is associated with increased pancreatic cancer risk.
Pratley, Richard; Saeed, Zeb I; Casu, Anna · Review
RPEP-09089 · 2024Semaglutide reduced the composite outcome of heart failure events or cardiovascular death (HR 0.73, meaning a 27% reduction, p = 0.0005). When broken down, it reduced heart failure events alone by 27% (HR 0.73, p = 0.0068) and cardiovascular death alone by 29% (HR 0.71, p = 0.0036).
About 19% of participants had heart failure at baseline. The benefit was consistent in both groups: those with pre-existing heart failure (HR 0.73, p = 0.034) and those without (HR 0.72, p = 0.003). Patients with more severe heart failure (NYHA class III) and reduced ejection fraction had higher overall event rates regardless of treatment.
Pratley, Richard E; Tuttle, Katherine R; Rossing, Peter; Rasmussen, Søren; Perkovic, Vlado; Nielsen, Olav Wendelboe; Mann, Johannes F E; MacIsaac, Richard J; Kosiborod, Mikhail N; Kamenov, Zdravko; Idorn, Thomas; Hansen, Marco Bo; Hadjadj, Samy; Bakris, George; Baeres, Florian M M; Mahaffey, Kenneth W · Randomized Controlled Trial
RPEP-09090 · 2024Among diabetes medications studied for stroke prevention, GLP-1 receptor agonists (specifically semaglutide and dulaglutide) reduced the risk of ischemic stroke in people with type 2 diabetes. Pioglitazone significantly reduced recurrent stroke risk. DPP-4 inhibitors, SGLT2 inhibitors, and insulin did not affect stroke incidence. Metformin monotherapy showed possible stroke reduction but evidence was less definitive.
Prentza, Vasiliki; Pavlidis, George; Ikonomidis, Ignatios; Pililis, Sotirios; Lampsas, Stamatios; Kountouri, Aikaterini; Pliouta, Loukia; Korakas, Emmanouil; Thymis, John; Palaiodimou, Lina; Tsegka, Aikaterini; Markakis, Konstantinos; Halvatsiotis, Panagiotis; Tsivgoulis, Georgios; Lambadiari, Vaia · Systematic Review
RPEP-09091 · 2024SGLT2 inhibitors with metformin reduced gout incidence by 25% compared to metformin alone (HR 0.75, p < 0.0001). SGLT2 inhibitors with insulin reduced gout by 17% versus insulin alone (HR 0.83, p < 0.0001).
GLP-1 receptor agonists showed no significant difference in gout incidence versus either metformin or insulin controls.
When SGLT2 inhibitors were compared directly to GLP-1 drugs, they had lower gout rates in both the metformin group (HR 0.77, p < 0.0001) and the insulin group (HR 0.82, p < 0.0001).
Preston, Frank G; Anson, Matthew; Riley, David R; Ibarburu, Gema H; Henney, Alexander; Lip, Gregory Y H; Cuthbertson, Daniel J; Alam, Uazman; Zhao, Sizheng S · Cohort Study
RPEP-09092 · 2024The POSEIDON database contains over 2,300 experimental entries with quantitative uptake values (how much peptide actually entered cells) and physicochemical properties for 1,315 peptides. Using this data plus genomic features of different cell lines, the team trained a regression model.
The model achieved a Pearson correlation of 0.87, Spearman correlation of 0.88, and r-squared of 0.76 on an independent test set. This means the model explains about 76% of the variation in peptide uptake across different cell types.
Preto, António J; Caniceiro, Ana B; Duarte, Francisco; Fernandes, Hugo; Ferreira, Lino; Mourão, Joana; Moreira, Irina S · Computational/Database
RPEP-09093 · 2024NPY13-36 was injected directly into the brain during either the ischemic phase (while blood flow was blocked) or the reperfusion phase (when blood flow returned). The drug was effective when given during reperfusion, not during ischemia.
During reperfusion, NPY13-36 reduced infarct size (the dead brain area), improved gait, mobility, and sensorimotor function, and restored normal microcirculatory response to nitric oxide synthase blockade. The vasoprotective effect was a new discovery, meaning the drug protected the tiny blood vessels in the brain, not just the neurons.
Przykaza, Łukasz; Domin, Helena; Śmiałowska, Maria; Stanaszek, Luiza; Boguszewski, Paweł M; Kozniewska, Ewa · Animal Study
RPEP-09094 · 2024During the 16-week intervention, participants achieved significantly lower HbA1c (40 vs 51 mmol/mol, p < 0.0001) and lost more weight (3.3% vs 1.9%, p = 0.02) compared to controls.
After stopping all glucose-lowering drugs, there was a 37% lower hazard of diabetes relapse in the intervention group (HR 0.63, 95% CI 0.45-0.88, p = 0.007). However, this benefit did not last. At 12 weeks post-intervention, remission rates were 17.7% vs 12.5% (not significant). At 52 weeks, they were 6.3% vs 3.8% (not significant).
The key takeaway: intensive metabolic intervention delayed relapse but could not sustain remission once drugs were stopped.
Punthakee, Zubin; Hall, Stephanie; McInnes, Natalia; Sherifali, Diana; Tsiplova, Kate; Kirabo, Faith R; Ransom, Thomas P P; Harris, Stewart B; Lochnan, Heather A; Sigal, Ronald J; Ghosh, Mahua; Spaic, Tamara; Gerstein, Hertzel C · Randomized Controlled Trial
RPEP-09095 · 2024Among the novel agents studied in animal models, liraglutide showed neuroprotective and anti-inflammatory effects against vincristine-induced nerve damage. Oxytocin demonstrated analgesic properties. Other promising candidates included ulinastatin (enzyme inhibitor), aripiprazole (antipsychotic), anakinra (IL-1 receptor antagonist), and thioctic acid (antioxidant). All work through different mechanisms including reducing inflammation, protecting nerve integrity, and modulating pain pathways.
Pușcașu, Ciprian; Negreș, Simona; Zbârcea, Cristina Elena; Chiriță, Cornel · Review
RPEP-09097 · 2024The primary endpoint (death or heart failure rehospitalization at 1 year) occurred in 31 of 104 patients. Optimal GDF-15 cut-offs were 5115.5 pg/mL (admission), 4145 pg/mL (discharge), and 4218.5 pg/mL (30 days). NT-proBNP cut-offs were 6011 ng/L, 1250 ng/L, and 1456.5 ng/L at the same timepoints. Patients with both markers above cut-off had the highest risk at all three timepoints. The combined 30-day model achieved the best prediction (AUC 0.75) for the composite endpoint, outperforming single biomarker measurements.
Płonka, Joanna; Klus, Anna; Wężyk, Natalia; Dąbrowska, Klaudia; Rzepiela, Lidia; Gawrylak-Dryja, Ewa; Nalewajko, Krzysztof; Feusette, Piotr; Gierlotka, Marek ·
RPEP-09099 · 2024The researchers created a microphysiological system (MPS), a tiny interconnected network of human fat cells, liver cells, and inflammatory immune cells (macrophages). When macrophages inflamed the fat cells, the liver cells accumulated fat and stopped responding to insulin properly. This recreated the early stages of metabolic dysfunction-associated steatotic liver disease (MASLD, previously called NAFLD).
Semaglutide improved liver cell function in this system. The key discovery: semaglutide acted on the fat cells, not the liver cells. By calming the inflamed fat cells, semaglutide indirectly reduced liver fat accumulation and restored insulin sensitivity throughout the system.
Qi, Lin; Groeger, Marko; Sharma, Aditi; Goswami, Ishan; Chen, Erzhen; Zhong, Fenmiao; Ram, Apsara; Healy, Kevin; Hsiao, Edward C; Willenbring, Holger; Stahl, Andreas · In Vitro
RPEP-09100 · 2024Using ado-trastuzumab emtansine (T-DM1, a breast cancer ADC) as the test drug, researchers identified conjugated peptides (the spots where the toxic drug attaches to the antibody) using a proteomics approach. They then built a semi-quantitative measurement method using liquid chromatography-mass spectrometry.
After optimizing sample preparation to reduce blood serum interference, they validated the method and applied it to measure stability at different conjugation sites on T-DM1. The results showed clear differences in stability between sites. Some attachment points lost their drug payload faster than others in serum.
Qi, Meiling; Zhu, Chenyue; Chen, Yi; Wang, Chenxi; Ye, Xinyuan; Li, Sen; Cheng, Zhongzhe; Jiang, Hongliang; Du, Zhifeng · Method Development
RPEP-09101 · 2024Both L. salivarius 23-006 and L. paracasei 23-008 reduced skin lesions, skin inflammatory infiltrates, and inflammatory factor expression in the LL-37 rosacea mouse model. The combination of both strains produced the strongest effects.
The probiotics worked by inhibiting the TLR2/MyD88/NF-kB signaling pathway, which is the same pathway LL-37 uses to trigger rosacea inflammation. They also reduced cathelicidin LL-37 expression itself, breaking the cycle. Gut microbiome analysis showed the probiotics increased Lactobacillus levels while reducing Coprococcus and Oscillospira, and strengthened the intestinal barrier.
Postbiotics (the metabolic byproducts of the bacteria, used without live bacteria) also helped but were less effective than live probiotic treatment.
Qi, Xinyue; Xiao, Yiran; Zhang, Xinfeng; Zhu, Zhenlin; Zhang, Hongyan; Wei, Jing; Zhao, Zhixiang; Li, Ji; Chen, Tingtao · Animal Study
RPEP-09102 · 2024HNSS showed a 2-fold improvement in brain distribution compared to HNG alone. Its structure mimics cell-penetrating peptides, which explains the enhanced brain entry.
Inside the brain, HNSS worked on multiple fronts. It targeted mitochondria and scavenged reactive oxygen species (damaging molecules). It activated the STAT3 pathway, which helps cell survival. It also blocked amyloid beta from clumping into the toxic oligomers and fibrils that characterize Alzheimer's. HNSS reduced amyloid deposits in neurons and helped immune cells in the brain (microglia) clear amyloid.
In 3xTg-AD transgenic mice (a standard Alzheimer's model), HNSS treatment prevented brain neuron loss and improved cognitive performance on memory tests.
Qian, Kang; Yang, Peng; Li, Yixian; Meng, Ran; Cheng, Yunlong; Zhou, Lingling; Wu, Jing; Xu, Shuting; Bao, Xiaoyan; Guo, Qian; Wang, Pengzhen; Xu, Minjun; Sheng, Dongyu; Zhang, Qizhi · Animal Study
RPEP-09103 · 2024Osteocytes (the most common bone cells) secreted excess neuropeptide Y during osteoarthritis. This NPY promoted inflammation, osteoclast formation (cells that break down bone), and neurite outgrowth (nerve growth that contributes to pain).
Intermittent fasting reversed these effects. Culture medium from osteocytes of fasting mice did not trigger the same inflammatory and bone-destroying responses. When researchers genetically deleted NPY from osteocytes, intermittent fasting lost its beneficial effects on osteoarthritis. This proved that osteocyte NPY is the specific target through which fasting works.
The findings held in both surgically induced osteoarthritis (meniscus destabilization) and natural aging-induced osteoarthritis.
Qian, Yu-Xuan; Rao, Shan-Shan; Tan, Yi-Juan; Wang, Zun; Yin, Hao; Wan, Teng-Fei; He, Ze-Hui; Wang, Xin; Hong, Chun-Gu; Zeng, Hai-Jin; Luo, Yi; Duan, Yan-Xin; Zhu, Hao; Hu, Xin-Yue; Zou, Ling; Zhang, Yan; Liu, Bing-Bing; Wang, Zhen-Xing; Du, Wei; Chen, Chun-Yuan; Xie, Hui · Animal Study
RPEP-09104 · 2024Weight loss was dose-dependent and significant at all three dose levels compared to placebo:
- 5 mg: -8.07% body weight (about 7.5 kg lost)
- 10 mg: -10.79% body weight (about 11 kg lost)
- 15 mg: -11.83% body weight (about 11.5 kg lost)
All three doses also reduced BMI and waist circumference. The proportion of patients achieving meaningful weight loss thresholds (5%, 10%, 15%, 20%, and 25%) was significantly higher with tirzepatide at all dose levels. Beyond weight, tirzepatide reduced blood pressure, blood sugar, and lipid levels.
Qin, Wenhui; Yang, Jun; Ni, Ying; Deng, Chao; Ruan, Qinjuan; Ruan, Jun; Zhou, Peng; Duan, Kai · Meta Analysis
RPEP-09105 · 2024Patients receiving sacubitril/valsartan experienced faster resolution of chest tightness, shortness of breath, cough, and lung crackles compared to the control group. BNP (brain natriuretic peptide, a marker of heart stress) decreased more in the treatment group. Inflammatory markers IL-6, TNF-α, and procalcitonin also improved more with sacubitril/valsartan.
Heart function improved significantly in the treatment group but not the control group. Clinical lung infection scores and organ failure scores were better with treatment. Over 2 years, the readmission rate was lower in the sacubitril/valsartan group, though mortality did not differ.
Qin, Xiao; Li, Nannan; Zhang, Cuifen; Li, Shanshan; Bu, Fanli · Retrospective Cohort
RPEP-09106 · 2024Keratin peptides under 3 kDa (KEP1) showed the highest cell-penetrating ability at a concentration of 2 mg/mL. They delivered fluorescein-labeled insulin (FITC-INS) into Caco2 intestinal cells without covalent bonding, meaning the keratin peptides and insulin were simply mixed together.
The most effective keratin fragments were 8-19 amino acids long and included hydrophobic peptides (like RVVIEPSPVVV), PPII amphipathic peptides (like PPPVVVTFP), and cysteine-rich peptides (like LCAPTPCGPTPL). Uptake was energy-dependent and primarily used macropinocytosis. The peptides' rich hydrophobic residues and disulfide bonds contributed to their cell-penetrating ability.
Qin, Xiaojie; Guo, Yujie; Li, Ruilin; Bitter, Johannes H; Scott, Elinor L; Zhang, Chunhui · In Vitro
RPEP-09107 · 2024Cancer patients face elevated cardiovascular risk from both the cancer itself and cardiotoxic treatments. GLP-1 receptor agonists have shown multiple cardiovascular benefits in large diabetes trials: reduced atherosclerosis, heart failure prevention, and kidney protection.
The mechanisms involve activation of cAMP and PI3K/AKT pathways (which promote cell survival) and inhibition of NLRP-3 inflammasome and MyD88 (which drive inflammation). These same pathways are involved in chemotherapy-induced cardiac damage, suggesting GLP-1 drugs could offer cardioprotection during cancer treatment.
The review highlights that no dedicated trial has tested GLP-1 drugs specifically for cardiac protection in cancer patients.
Quagliariello, Vincenzo; Canale, Maria Laura; Bisceglia, Irma; Iovine, Martina; Giordano, Vienna; Giacobbe, Ilaria; Scherillo, Marino; Gabrielli, Domenico; Maurea, Carlo; Barbato, Matteo; Inno, Alessandro; Berretta, Massimiliano; Tedeschi, Andrea; Oliva, Stefano; Greco, Alessandra; Maurea, Nicola · Review
RPEP-09108 · 2024NOR-1202 showed route-dependent antiepileptic effects. Direct brain injection (intracerebroventricular) protected against pilocarpine-induced generalized seizures and mortality. In the kainic acid model, it improved survival but did not prevent seizures. Systemic administration (subcutaneous or intraperitoneal) showed no antiepileptic activity, suggesting the peptide cannot cross the blood-brain barrier. In a chronic temporal lobe epilepsy model, NOR-1202 did not significantly reduce spontaneous recurrent seizures.
Quintanilha, Maria Varela Torres; Gobbo, Giovanna de Azevedo Mello; Pinheiro, Gabriela Beserra; Souza, Adolfo Carlos Barros de; Camargo, Luana Cristina; Mortari, Marcia Renata · Animal Study
RPEP-09109 · 2024Tirzepatide's dual mechanism activating both GIP and GLP-1 receptors produces superior efficacy compared to GLP-1-only drugs. The review highlights several key advantages:
Glycemic control: tirzepatide produced larger HbA1c reductions than semaglutide, insulin, and other comparators in the SURPASS trial program. Weight loss: the SURMOUNT trials showed up to 22% body weight reduction in non-diabetic obese patients. Cardiovascular signals: emerging data suggests cardiovascular benefits, potentially setting a new treatment standard.
The review notes that tirzepatide's GIP component may add benefits beyond what GLP-1 alone provides, including potentially better preservation of bone and muscle mass during weight loss.
Rabbani, Syed Arman; El-Tanani, Mohamed; Matalka, Ismail I; Rangraze, Imran Rashid; Aljabali, Alaa A A; Khan, Mohammad Ahmed; Tambuwala, Murtaza M · Review
RPEP-09110 · 2024The nestin/hRAMP1 mice showed heightened sensitivity to CGRP's effects at lower doses compared to normal mice. They exhibited increased motion-induced thermoregulation changes (a surrogate for nausea) and greater postural sway (a measure of balance dysfunction). Male nestin/hRAMP1 mice specifically showed increased sway not seen in male controls.
Migraine blocker experiments were challenging to interpret, but the data suggests olcegepant (a CGRP receptor antagonist) could not reverse CGRP-induced or endogenous changes in these mice. Rizatriptan (a triptan) was ineffective in both the engineered mice and controls.
The authors propose this mouse model represents treatment-resistant migraine with vestibular features.
Rahman, Shafaqat M; Guo, Linda Jia; Minarovich, Carissa; Moon, Laura; Guo, Anna; Luebke, Anne E · Animal Study
RPEP-09111 · 2024Older mice (over 18 months, roughly equivalent to elderly humans) infected with mouse-adapted SARS-CoV-2 showed neurological symptoms including fever, dizziness, and nausea in two wild-type strains (C57BL/6J and 129/SvEv).
Olcegepant treatment protected against the permanent weight loss seen after infection. It also dramatically reduced IL-6 levels in both mouse strains. The most striking finding: CGRP-knockout mice (lacking the alpha-CGRP gene entirely) showed virtually no IL-6 release after infection.
The fever, dizziness, and nausea occurred in all older mice regardless of treatment, suggesting CGRP blockade acts on the inflammatory cascade rather than preventing initial neurological symptoms.
Rahman, Shafaqat M; Buchholz, David W; Imbiakha, Brian; Jager, Mason C; Leach, Justin; Osborn, Raven M; Birmingham, Ann O; Dewhurst, Stephen; Aguilar, Hector C; Luebke, Anne E · Animal Study
RPEP-09112 · 2024Researchers synthesized oleyl-conjugated peptides of increasing length: oleyl-(WRH)1 through oleyl-(WRH)4. The peptide/siRNA complexes were non-cytotoxic at the working concentration (N/P ratio 40, about 20 μM) against breast cancer (MDA-MB-231, MCF-7), ovarian cancer (SK-OV-3), and normal (HEK-293) cells after 72 hours.
Oleyl-(WRH)3 and oleyl-(WRH)4 showed the best siRNA delivery: about 60% and 75% cellular uptake respectively in MDA-MB-231 and SK-OV-3 cells. The complexes formed particles under 200 nm in diameter and remained stable in serum at N/P ratios of 40 or above.
Western blot confirmed oleyl-(WRH)4 silenced the STAT3 gene by approximately 75% in MDA-MB-231 breast cancer cells and 45% in SK-OV-3 ovarian cancer cells.
Rai, Mrigank Shekhar; Sajid, Muhammad Imran; Moreno, Jonathan; Parang, Keykavous; Tiwari, Rakesh Kumar · In Vitro
RPEP-09113 · 2024In the SUSTAIN-6 cardiovascular outcome trial, semaglutide was associated with approximately 75% increased risk of diabetic retinopathy (DR) worsening. This was a secondary endpoint, not the trial's primary focus. Cases were rare in absolute terms.
Insulin icodec (a novel once-weekly insulin) also showed increased DR worsening compared to daily insulin. No other recent antihyperglycemic agent (SGLT2 inhibitors, DPP-4 inhibitors, other GLP-1 drugs) was associated with DR worsening.
Importantly, after the SUSTAIN-6 finding, nearly all subsequent trials excluded patients with pre-existing diabetic retinopathy. This means the true risk in the most vulnerable population remains unclear. Dedicated semaglutide eye safety studies were underway at the time of publication.
The most at-risk patients are those with pre-existing high-risk DR, poor baseline blood sugar (where rapid improvement could trigger worsening), and those using insulin.
Rajagopal, Rithwick; McGill, Janet B · Review
RPEP-09114 · 2024Chemical hypoxia (using DNP) increased paracellular permeability in human colon by 52% (p = 0.003). Both somatostatin (2 μM) and octreotide (0.2 μM) prevented this increase whether given before or after the hypoxic insult.
In rat colon, hypoxia increased total epithelial conductance by 18% (p = 0.016) and macromolecule permeability (FITC-dextran movement) by 43% (p = 0.01). Octreotide pretreatment at 0.2 μM completely prevented both changes.
The mechanism involves IK channels (intermediate conductance potassium channels, KCa3.1/KCNN4) on the basolateral side of the epithelium. Hypoxia activates these channels, opening the paracellular pathway. Somatostatin and octreotide inhibit IK channels, keeping the gut barrier intact.
Rajput, Ibrahim; Rajendran, Vazhaikkurichi M; Nickerson, Andrew J; Lodge, J Peter A; Sandle, Geoffrey I · Ex Vivo
RPEP-09115 · 2024Appetite is regulated by two sets of neurons in the hypothalamus. POMC neurons (activated by satiety hormones) suppress appetite. NPY/AgRP neurons (activated by hunger signals) promote eating. Gut hormones modulate this balance.
After bariatric surgery, the key changes include: increased GLP-1 (which suppresses appetite and improves blood sugar), increased PYY (peptide YY, which signals fullness), increased oxyntomodulin (which reduces food intake), and decreased ghrelin (the hunger hormone).
The review highlights that GLP-1 receptor agonists pharmacologically replicate part of this post-surgical response. This explains their effectiveness for weight loss even without surgery. The review also notes that genetic testing can now identify monogenic and polygenic obesity, potentially guiding individualized treatment.
Ramasamy, Indra · Review
RPEP-09116 · 2024The review compared multiple CPP prediction tools using standard performance metrics (accuracy, sensitivity, specificity, Matthews correlation coefficient) on independent test datasets.
Commonly used algorithms include support vector machines (SVM), random forests (RF), gradient-boosted decision trees (GBDT), and various types of artificial neural networks (ANN). The review found that tool performance varies significantly depending on dataset size, feature encoding method, and the specific evaluation metrics used.
Key factors that affect prediction accuracy include: the size and quality of the training dataset, how peptide sequences are encoded as numerical features, and whether the tool uses sequence-based, structure-based, or hybrid features. The review emphasizes the importance of evaluating tools on independent test sets rather than cross-validation alone.
Ramasundaram, Maduravani; Sohn, Honglae; Madhavan, Thirumurthy · Review
RPEP-09117 · 2024Sixteen obese patients with IBD (9 Crohn's disease, 7 ulcerative colitis) received semaglutide 1.0 mg or liraglutide 3.0 mg for obesity. Their median starting BMI was 35.
At 6 months, median weight change was -6.2%. 58.3% (7 of 12 evaluable patients) achieved at least 5% weight loss. IBD activity scores showed no significant changes during follow-up, meaning the drugs did not trigger disease flares.
Side effects were mild. Nausea was the most common at 13.3%. One patient discontinued due to diarrhea. No serious adverse events were reported.
Ramos Belinchón, Clara; Martínez-Lozano, Helena; Serrano Moreno, Clara; Hernández Castillo, Diego; Lois Chicharro, Pablo; Ferreira Ocampo, Pablo; Marín-Jiménez, Ignacio; Bretón Lesmes, Irene; Menchén, Luis · Case Series
RPEP-09118 · 2024Neurokinin B at three doses (1 μg, 1 ng, and 10 pg) administered intraperitoneally for 12 days increased seminal vesicle weight, epithelial height, and seminal fructose levels in a dose-dependent manner. Senktide (an NK3R agonist) produced similar effects. SB222200 (an NK3R antagonist) slightly decreased these parameters.
Light microscopy showed increased epithelial height and folding in all neurokinin B and senktide groups. Immunohistochemistry for NK3 receptor expression showed no change with treatment, suggesting the receptor is constitutively expressed.
Critically, all effects reversed when rats were kept for 12 days without treatment, indicating the changes are stimulatory and reversible rather than permanent.
Ramzan, Muhammad Haris; Shah, Mohsin; Ramzan, Faiqah · Animal Study
RPEP-09119 · 2024After approximately 26 weeks on IDegLira:
- HbA1c decreased by 1.3% (from 9.1% to 7.8%, p < 0.0001)
- Body weight decreased by 1 kg (from 76.1 to 75.1 kg, p < 0.0001)
- No severe hypoglycemic events observed
- Mean final IDegLira dose: 21.3 units
These results were achieved in patients who had previously been on basal insulin (with or without oral diabetes drugs) and were not reaching their blood sugar targets. The combination provided better control with modest weight loss rather than the weight gain typically seen with intensified insulin therapy.
Ramírez-Rincón, Alex; Henao-Carrillo, Diana; Omeara, Miguel; Oliveros, Julio; Assaf, José; Ordóñez, Jaime E; Prasad, Preethy; Alzate, María Alejandra · Retrospective Cohort
RPEP-09120 · 2024Compared to tirzepatide 5 mg:
- 10 mg: additional 19% HbA1c reduction (MD: -0.19), additional 1.96 kg weight loss
- 15 mg: additional 31% HbA1c reduction (MD: -0.32), additional 3.31 kg weight loss, and improved fasting glucose (MD: -6.71 mg/dL)
The dose-response relationship was clear and consistent across the 10 studies. Higher doses produced incrementally better metabolic outcomes.
For safety, gastrointestinal events were numerically higher with increasing doses but without reaching statistical significance. There were no significant differences across doses for death, nausea, diarrhea, vomiting, dyspepsia, decreased appetite, injection site reactions, hypoglycemia, treatment discontinuation, or serious adverse events.
Rangwala, Hussain Sohail; Fatima, Hareer; Ali, Mirha; Mustafa, Muhammad Saqlain; Shafique, Muhammad Ashir; Rangwala, Burhanuddin Sohail; Abbas, Syed Raza · Network Meta Analysis
RPEP-09121 · 2024The peptide inhibitors specifically target the primary binding interface between TANGO1 and cTAGE5, two proteins required for collagen export from the endoplasmic reticulum. Treatment reduced protein levels of both TANGO1 and cTAGE5, blocking the secretion of multiple extracellular matrix components including collagens, fibrillin, and fibronectin.
In zebrafish, the peptide inhibitors altered tissue architecture and reduced granulation tissue formation during wound healing. In human dermal fibroblasts and cells from scleroderma patients (who have generalized fibrosis), the inhibitors reduced secretion of ECM proteins.
Raote, Ishier; Rosendahl, Ann-Helen; Häkkinen, Hanna-Maria; Vibe, Carina; Küçükaylak, Ismail; Sawant, Mugdha; Keufgens, Lena; Frommelt, Pia; Halwas, Kai; Broadbent, Katrina; Cunquero, Marina; Castro, Gustavo; Villemeur, Marie; Nüchel, Julian; Bornikoel, Anna; Dam, Binita; Zirmire, Ravindra K; Kiran, Ravi; Carolis, Carlo; Andilla, Jordi; Loza-Alvarez, Pablo; Ruprecht, Verena; Jamora, Colin; Campelo, Felix; Krüger, Marcus; Hammerschmidt, Matthias; Eckes, Beate; Neundorf, Ines; Krieg, Thomas; Malhotra, Vivek · In Vitro/Animal
RPEP-09122 · 2024Oxytocin shows dose-dependent effects on alcohol use behavior: low doses do not significantly affect drinking or tolerance, but higher doses given before alcohol exposure produce varying behavioral and physiological results. In preclinical (animal) studies, oxytocin reduced withdrawal symptoms and alcohol self-administration. In clinical (human) studies, oxytocin may decrease neural cue reactivity (how strongly the brain responds to alcohol-related cues) and withdrawal symptoms.
The timing and dose of oxytocin appear critical — the peptide seems to work by strengthening stress-coping mechanisms and reducing anxiety, which are key drivers of alcohol craving and relapse. However, results are inconsistent across studies, and the optimal dosing and treatment protocols remain unclear.
Rastogi, Kriti; Weerts, Elise M; Ellis, Jennifer D · Review
RPEP-09123 · 2024CRAMP18-35 (a fragment of mouse cathelicidin) was conjugated to chitosan and hydroxypropyl chitosan using copper-catalyzed azide-alkyne cycloaddition (CuAAC, a click chemistry reaction). The degree of substitution was 0.20 for chitosan and 0.13 for HPC conjugates.
The conjugates showed selective antibacterial activity against Gram-negative bacteria (E. coli and P. aeruginosa) and lacked activity against Gram-positive bacteria (S. aureus and E. faecalis). This selectivity was a notable finding because the free peptide is typically active against both types.
Rathinam, Sankar; Sørensen, Kasper K; Hjálmarsdóttir, Martha Á; Thygesen, Mikkel B; Másson, Már · In Vitro
RPEP-09125 · 2024Capromorelin acts on the growth hormone secretagogue receptor 1a (GHSR-1a), the same receptor activated by the natural hunger hormone ghrelin. When natural ghrelin production is disrupted, capromorelin substitutes to stimulate growth hormone release and appetite.
In dogs, capromorelin (Entyce) increases food intake and is FDA-approved for appetite stimulation. In cats, capromorelin (Elura) is approved for managing weight loss associated with chronic kidney disease. The drug also stimulates growth hormone and IGF-1, which may help prevent muscle wasting and cachexia.
Rathore, Manisha; Das, Nabanita; Ghosh, Nayan; Guha, Rajdeep · Review