RPEP-07622 · 2023Two novel peptides were identified from rice bran protein hydrolysate: FDGSPVGY (840.4 Da) with an ACE-inhibitory IC50 of 0.079 mg/mL (94.05 μM), and VFDGVLRPGQ (1086.6 Da) with an IC50 of 0.093 mg/mL (85.59 μM).
Molecular docking analysis revealed that both peptides interact with the ACE receptor protein through hydrogen bonding and hydrophobic interactions, providing a structural explanation for their inhibitory activity.
In EA.hy926 endothelial cells, both peptides promoted nitric oxide (NO) release and reduced endothelin-1 (ET-1) levels — two complementary mechanisms that would lower blood pressure by relaxing blood vessels and reducing vasoconstriction.
Zhang, Lingyu; Miao, Jianyin; Guo, Junbin; Liu, Jie; Xia, Zhen; Chen, Bingbing; Ma, Feng; Cao, Yong ·
RPEP-07634 · 2023Cryo-EM analysis of SSTR2-Gi protein complexes revealed the detailed binding modes and activation mechanisms for both octreotide (a peptide analog) and paltusotine (a small molecule). The two drugs show distinct signal bias profiles — meaning they activate different downstream signaling pathways to different degrees despite binding the same receptor.
The structural data explains the molecular basis of subtype selectivity (why these drugs prefer SSTR2 over other somatostatin receptor subtypes) and signal bias (why they trigger some cellular responses more than others). This mechanistic understanding is directly relevant to why a subset of acromegaly patients have poor responses to current somatostatin analogs.
Zhao, Jie; Fu, Hong; Yu, Jingjing; Hong, Weiqi; Tian, Xiaowen; Qi, Jieyu; Sun, Suyue; Zhao, Chang; Wu, Chao; Xu, Zheng; Cheng, Lin; Chai, Renjie; Yan, Wei; Wei, Xiawei; Shao, Zhenhua · Structural Biology
RPEP-07641 · 2023MOTS-c is encoded by the 12S rRNA region of the mitochondrial genome and is expressed across multiple tissues and found in blood plasma. Key properties: translocates from mitochondria to the nucleus during metabolic stress to regulate gene expression, improves glucose metabolism in skeletal muscle, plasma levels decrease with age, and demonstrates benefits in preclinical models of diabetes, obesity, insulin resistance, cardiovascular disease, inflammation, and aging. The review also discusses synthetic biology approaches for MOTS-c production and delivery.
Zheng, Yuejun; Wei, Zilin; Wang, Tianhui ·
RPEP-07645 · 2023After enzymatic hydrolysis and two rounds of chromatographic purification, researchers identified two key peptides from kuruma shrimp head protein. The antibacterial peptide VTVP showed minimum inhibitory concentration (MIC) values ranging from 1.62 to 8.03 mM against all tested pathogens. The ACE inhibitory peptide ARL/I demonstrated an IC50 value of 125.58 µM and was confirmed as a competitive inhibitor through Lineweaver-Burk analysis.
Molecular docking revealed that ARL/I binds to ACE primarily through hydrogen bonds and forms a coordinate bond with the zinc ion at the enzyme's active site. Importantly, neither peptide showed hemolytic activity against rabbit red blood cells, indicating a favorable safety profile.
Zhou, Jie; Han, Qiuyu; Koyama, Tomoyuki; Ishizaki, Shoichiro ·
RPEP-07648 · 2023The neuropeptide substance P (SP) and its receptor NK-1R were found to be elevated in both patients with chronic kidney disease and in mice with induced kidney obstruction. Higher SP/NK-1R levels correlated with worse kidney fibrosis and declining kidney function.
Adding substance P to mice with kidney obstruction worsened inflammation and fibrosis, while genetically knocking out NK-1R or blocking it with a drug significantly reduced these effects. The researchers uncovered the mechanism: a transcription factor called TFAP4 drives NK-1R production, and once substance P activates NK-1R, it triggers the JNK/p38 signaling pathways. This causes kidney tubular cells to stop growing, undergo programmed cell death, and switch on scar-producing genes.
Zhu, Enyi; Liu, Yang; Zhong, Ming; Liu, Yu; Jiang, Xi; Shu, Xiaorong; Li, Na; Guan, Hui; Xia, Yin; Li, Jinhong; Lan, Hui-Yao; Zheng, Zhihua · Human And Animal
RPEP-07650 · 2023Across 6 RCTs involving 195 women, oxytocin's effects on postpartum depression were mixed. For emotion: one trial showed oxytocin alleviated depressive mood, two showed no effect (though one found reduced negative thoughts in healthy mothers), and one actually showed oxytocin worsened depression. For cognition: four trials generally found oxytocin enhanced postpartum women's perception of their relationship with their infants. The review concluded that oxytocin may improve mother-infant cognitive bonding but its effects on depressive mood remain uncertain and contradictory.
Zhu, Jialei; Jin, Jing; Tang, Jing ·
RPEP-07652 · 2023Pancreatic polypeptide (PP) — a hormone released from the pancreas — suppresses appetite by activating Y4 receptors in the brain, producing satiety in both animals and humans. Beyond appetite control, PP also affects the insulin-producing beta cells of the pancreas, with an acute insulin-suppressing effect.
Intriguingly, sustained activation of related Y-family receptors (Y1) improves beta-cell survival, preserves beta-cell identity, and enhances insulin secretion — raising the possibility that long-acting Y4 agonists could provide similar anti-diabetic benefits. However, PP's extremely short half-life in the blood has prevented its therapeutic development. Engineering enzyme-resistant, long-acting versions will be necessary to test its clinical potential.
Zhu, Wuyun; Tanday, Neil; Flatt, Peter R; Irwin, Nigel · Review
RPEP-07658 · 2024The guidelines establish a comprehensive framework for MASLD management with several key recommendations:
- Case-finding using non-invasive tests (FIB-4 score, then transient elastography) in patients with cardiometabolic risk factors
- Lifestyle modification as the foundation: weight loss, dietary changes, exercise, no alcohol
- Incretin-based therapies (semaglutide, tirzepatide) recommended for optimal management of comorbidities in MASLD patients with type 2 diabetes or obesity
- Resmetirom recommended as MASH-targeted treatment for non-cirrhotic patients with significant fibrosis (stage ≥2)
- Bariatric surgery as an option for MASLD patients with obesity
- No MASH-targeted pharmacotherapy recommended for cirrhotic stage
·
RPEP-07672 · 2024The disulfide bond in the designed thanatin analog peptide VF16QK is essential for its antibacterial activity. Only the disulfide-bonded form showed bacterial growth inhibition, while the Cys-to-Ser variant (VF16QKSer) lacking the disulfide bond was inactive. The two forms showed vastly different 3D structures, bacterial membrane permeabilization abilities, LPS-outer membrane interactions, and binding to the target periplasmic protein LptAm. This contrasts with other β-hairpin antimicrobial peptides (protegrin, tachyplesin) where disulfide bonds are dispensable.
Abdullah, Swaleeha Jaan; Guan, Jia Sheng; Mu, Yuguang; Bhattacharjya, Surajit ·
RPEP-07676 · 2024Researchers built an inexpensive, flexible biosensor from a common overhead projector (OHP) sheet that can detect Neuropeptide Y (NPY) in sweat with remarkable sensitivity. The sensor detected NPY across a wide concentration range (1 pg/mL to 1 μg/mL) with a detection limit of just 0.68 pg/mL and good linearity (R² = 0.9841).
The sensor showed excellent selectivity for NPY even in the presence of other molecules commonly found in sweat (TNF-α, cortisol, IL-6). It maintained stability for 13 days and successfully detected NPY spiked into artificial sweat at 100 pg/mL, demonstrating potential for real-world wearable health monitoring applications.
Aerathupalathu Janardhanan, Jayakrishnan; She, Jia-Wei; Yu, Hsiao-Hua · Basic Research
RPEP-07679 · 2024Vasoactive intestinal peptide (VIP) protects the gut from radiation damage by promoting intestinal stem cell differentiation and regeneration. VIP drove intestinal epithelial cells toward a secretory phenotype primarily through the p38 MAPK signaling pathway and modulated the proliferation of Lgr5+ progenitor cells (intestinal stem cells). After radiation injury, these stem cells became more responsive to VIP's effects, and VIP strongly promoted epithelial regeneration. Critically, these findings held in live mice — VIP injections significantly reduced radiation-induced intestinal damage after abdominal irradiation with 12 Gy.
Agibalova, Tatiana; Hempel, Anneke; Maurer, H Carlo; Ragab, Mohab; Ermolova, Anastasia; Wieland, Jessica; Waldherr Ávila de Melo, Caroline; Heindl, Fabian; Giller, Maximilian; Fischer, Julius Clemens; Tschurtschenthaler, Markus; Kohnke-Ertel, Birgit; Öllinger, Rupert; Steiger, Katja; Demir, Ihsan Ekin; Saur, Dieter; Quante, Michael; Schmid, Roland M; Middelhoff, Moritz · Animal Study
RPEP-07680 · 2024Using GHSR-eGFP reporter mice, fluorescent ghrelin, and anti-GLP-1R antibodies, the team mapped receptor co-expression across the mouse brain. GHSR+ and GLP-1R+ neurons were largely segregated, with the highest overlap in the arcuate nucleus of the hypothalamus, where 15-20% of GHSR+ cells also expressed GLP-1R. RNA-sequencing data from both mouse and human brains confirmed that double-positive cells represent less than 10% of all GHSR+ or GLP-1R+ neurons.
In patch-clamp experiments, the researchers made the first demonstration that liraglutide-activated GLP-1R inhibits presynaptic calcium channels. Critically, when both receptors were present on the same cell, activating one attenuated the inhibitory effect of the other — showing direct molecular crosstalk between the ghrelin and GLP-1 signaling pathways.
Aguggia, Julieta; Fernandez, Gimena; Cassano, Daniela; Mustafá, Emilio R; Rodríguez, Silvia S; Cantel, Sonia; Fehrentz, Jean-Alain; Raingo, Jesica; Schiöth, Helgi B; Habib, Abdella M; De Francesco, Pablo N; Perello, Mario ·
RPEP-07695 · 2024After 12 months of GLP-1RA therapy in 54 T2DM patients (30 on dulaglutide, 24 on semaglutide), bone turnover markers and adiponectin significantly increased while myostatin showed a modest but significant reduction. Lumbar spine BMD by DXA decreased significantly, though the decrease by REMS was not significant. Trabecular bone score showed marginal improvement. Femoral BMD showed modest but significant reduction by both DXA and REMS. The authors interpret the combined findings as preservation of bone quality with reactivation of bone turnover.
Al Refaie, Antonella; Baldassini, Leonardo; Mondillo, Caterina; Ceccarelli, Elena; Tarquini, Roberto; Gennari, Luigi; Gonnelli, Stefano; Caffarelli, Carla ·
RPEP-07711 · 2024In this cohort of 205 patients, dulaglutide 1.5 mg weekly produced significant improvements in multiple outcomes at both 6 and 12 months compared to baseline. Weight, BMI, HbA1c, and fasting blood sugar all improved significantly.
The patient population was notable for the severity and duration of their disease: approximately 33% had diabetes for more than 20 years and 41.4% had class III (severe) obesity. Despite this challenging patient profile, dulaglutide delivered meaningful glycemic and weight benefits. Side effects were predominantly gastrointestinal, with nausea (52%) and fatigue (28%) being the most commonly reported.
Albargawi, Mashael Saad; Alharbi, Rawan Naser; Alajlani, Mohammad Abbas; Abdulaal, Ibtihal Abdulwarith; Aldakhil, Lina Othman ·
RPEP-07713 · 2024Substance P and NK-1R were overexpressed in all 43 human adamantinomatous craniopharyngioma (ACP) samples compared to healthy pituitary gland tissue. This is reported for the first time in this tumor type.
Substance P expression was widespread throughout the tumor and preferentially localized in the nucleus rather than the cytoplasm of tumor cells. Areas of glial reaction and endothelial cells also expressed SP, primarily in cell nuclei.
NK-1R was expressed mainly in the glial reaction zone, particularly in the nuclei and membranes of inflammatory cells, and in endothelial cells and fibroblasts of tumor blood vessels. Notably, tumor cells themselves did not show significant NK-1R expression, suggesting the peptide-receptor signaling operates primarily through the tumor microenvironment rather than directly on tumor cells.
Alcaide, Carlos; Perez, Francisco; Esteban, Francisco; Muñoz, Miguel ·
RPEP-07715 · 2024GLP-1 receptor agonists reduced the risk of hypocalcemia by 51% (2.7% vs 5.5%, RR 0.49) but doubled the risk of hypercalcemia (2.3% vs 1.1%, RR 2.02) compared to matched controls. Tirzepatide showed the strongest effects, reducing hypocalcemia by 63% while increasing hypercalcemia by 85%. GLP-1 RA use was also associated with significantly reduced emergency visits (RR 0.57), hospitalizations (RR 0.40), cardiovascular events, and all-cause mortality (HR 0.27). The hypocalcemia-protective effect was most pronounced in the first 6 months.
Alenezi, Bandar T; Elfezzani, Nadra; Uddin, Rukhsana; Patel, Hinali; Chester, Sydney; Abdelmaksoud, Ahmed; Hussein, Mohammad H; Zaitone, Sawsan A; Fawzy, Manal S; Aiash, Hani; Toraih, Eman A ·
RPEP-07719 · 2024GLP-1 receptor agonists have evolved from single-target drugs into dual and triple receptor agonists that represent the cutting edge of metabolic therapy. Single GLP-1RAs (semaglutide, liraglutide) effectively lower HbA1c, reduce weight, protect against cardiovascular events, and improve kidney health. Dual agonists like tirzepatide (GLP-1/GIP) produce even greater weight loss and glucose control by activating two incretin pathways simultaneously.
The next frontier is triple agonists — like retatrutide (GLP-1/GIP/glucagon) — which add glucagon receptor activation to increase energy expenditure and fat burning on top of appetite suppression and glucose control. These multi-agonist peptides represent the future direction of incretin-based therapy for both type 2 diabetes and obesity.
Alfaris, Nasreen; Waldrop, Stephanie; Johnson, Veronica; Boaventura, Brunna; Kendrick, Karla; Stanford, Fatima Cody · Review
RPEP-07720 · 2024The review establishes that NAFLD progresses through steatosis (fat accumulation) to non-alcoholic steatohepatitis (NASH, with inflammation/fibrosis) to cirrhosis and hepatocellular carcinoma. NAFLD is both a consequence and contributor to metabolic syndrome. No pharmacological agents are currently approved for NAFLD or NASH. Semaglutide's glycemic control and weight loss properties position it as a promising candidate, with evidence suggesting benefits for individuals with NAFLD through multiple metabolic pathways.
Alfawaz, Sultan; Burzangi, Abdulhadi; Esmat, Ahmed ·
RPEP-07723 · 2024Current incretin hormone agonists — liraglutide (SCALE trials), semaglutide (STEP trials), and tirzepatide (SURMOUNT-1) — have demonstrated remarkable efficacy in promoting weight loss and improving metabolic outcomes for obesity. The next generation of obesity drugs in development includes oral GLP-1 receptor agonists, triple agonists targeting GLP-1/GIP/glucagon receptors simultaneously, GLP-1/glucagon receptor co-agonists, oral GIP/GLP-1 co-agonists, and combinations of long-acting amylin receptor agonists with GLP-1 receptor agonists.
Alhomoud, Ibrahim S; Talasaz, Azita H; Chandrasekaran, Preethi; Brown, Roy; Mehta, Anurag; Dixon, Dave L ·
RPEP-07726 · 2024Semaglutide treatment produced significant real-world improvements across all key diabesity outcomes. Mean body weight decreased from 110.4 kg at baseline to 99.9 kg at 12 months and 96.8 kg at latest follow-up (approximately 13.6 kg total loss). HbA1c improved from 82 mmol/mol at baseline to 67 mmol/mol at 12 months and 71 mmol/mol at latest follow-up.
Insulin requirements also decreased, with mean daily doses dropping from 95 units at baseline to 76.5 units at latest follow-up — a roughly 20% reduction. Side effects were mild and primarily gastrointestinal, improving with continued use.
Alkhalifah, Mohammed; Afsar, Hafsa; Shams, Anindya; Blaibel, Dania; Chandrabalan, Vishnu; Pappachan, Joseph M ·
RPEP-07728 · 2024Across large-scale RCTs involving 17,327 participants with an average follow-up of ~2.9 years, sacubitril/valsartan compared to ACE inhibitors and ARBs showed:
- Notable reduction in NT-proBNP levels (a peptide biomarker of heart failure severity)
- Prevention of further deterioration in renal function
- Decreased hospitalizations for heart failure
- No increased risk of cardiovascular mortality
- Benefits observed across different types of heart failure and regardless of renal status
Almansouri, Naiela E; Bakkannavar, Saloni; Faheem, Youmna; Jaiswal, Amisha; Shergill, Kainaat; Boppana, Kusalik; Nath, Tuheen Sankar ·
RPEP-07729 · 2024After three months of erenumab treatment, the 26 migraine patients showed a median decrease of 13 points on the MIDAS disability scale. No statistically significant differences were found between genders or between erenumab dosage groups, but trends toward improvement were observed in all subgroups. The lack of statistical significance is attributed to the small sample size and absence of a control group.
Almarzooqi, Ali; Zidan, Marwan ·
RPEP-07738 · 2024NY-ESO-1 serves a dual role as both a tumor-associated antigen and its own adjuvant, potentially functioning as a damage-associated molecular pattern. It elicits strong humoral immune responses with antibody frequencies correlating with disease progression. Multiple therapeutic approaches have shown promise: peptide/protein vaccines, DNA/mRNA vaccines, bacterial and viral vector delivery, dendritic cell vaccines, artificial adjuvant vector cells, and TCR-engineered T cells. Next-generation NY-ESO-1 T-cell products and integration with lymph node-targeted vaccines are addressing current efficacy challenges.
Alsalloum, Alaa; Shevchenko, Julia A; Sennikov, Sergey ·
RPEP-07743 · 2024At non-cytotoxic concentrations, most of the 21 tested venoms activated inflammatory mediator release: IL-6, IL-8, and TNF-α from chondrocytes, synoviocytes, and macrophages, and substance P from neuron-like cells. Viperidae snake venoms were more inflammatory than Elapidae venoms, and arthropod venoms were generally less inflammatory than snake venoms.
Notably, some venoms induced IL-10 (anti-inflammatory) release from macrophages. The scorpion Buthus occitanus venom was unique — it induced IL-10 release without increasing inflammatory cytokine production from macrophages, making it the most promising candidate for anti-inflammatory drug discovery. The platform also measured neuropeptide release (substance P and β-endorphin) from differentiated sensory neuron-like cells, connecting venom effects to pain modulation pathways.
Alvarez-Flores, Miryam Paola; Correia Batista, Isabel de Fatima; Villas Boas, Isadora Maria; Bufalo, Michelle Cristiane; de Souza, Jean Gabriel; Oliveira, Douglas Souza; Bonfá, Giuliano; Fernandes, Cristina Maria; Marques Porto, Rafael; Lichtenstein, Flavio; Picolo, Gisele; Tambourgi, Denise V; Chudzinski-Tavassi, Ana Marisa; Ibañez, Olga Célia Martinez; Teixeira, Catarina ·
RPEP-07746 · 2024After 12 weeks of combined diet (1,000–1,500 kcal/day) and exercise (at least 5,000 steps/day), obese individuals showed significant changes in appetite-regulating peptide hormones: ghrelin (the hunger hormone) decreased significantly, while PYY (a satiety hormone) increased significantly. These shifts support better appetite control and weight maintenance.
However, even after the intervention, the obese group's GLP-1 and PYY levels still did not reach the levels seen in healthy-weight controls. This suggests that while diet and exercise improve appetite hormone signaling, they may not fully normalize the peptide imbalances associated with obesity.
Alyar, Gülşah; Umudum, Fatma Zuhal; Akbaş, Nergis · Clinical Trial
RPEP-07748 · 2024Humanin-G produced several protective effects after hemorrhagic shock:
• Ameliorated histological lung damage in all groups — male and female, regardless of AMPKα1 status
• Reduced lung neutrophil infiltration in male and female AMPKα1 wild-type mice only — not in knockouts, indicating this effect requires AMPKα1
• Improved mean arterial blood pressure in male AMPKα1 knockout mice
• Activated AMPKα in lung tissue (cytosolic and nuclear) in wild-type mice
• Did not modify STAT3 activation
Key sex differences emerged: male wild-type mice had more pronounced neutrophil infiltration than females, and male AMPKα1 knockout mice experienced significant blood pressure declines after resuscitation compared to male wild-types. Hemorrhagic shock downregulated AMPKα1/α2 catalytic subunits in wild-type mice.
Amman, Allison M; Wolfe, Vivian; Piraino, Giovanna; Ziady, Assem; Zingarelli, Basilia ·
RPEP-07755 · 2024Researchers discovered that the gamma-core motif — an ancient structural element found in many cysteine-rich antimicrobial peptides across different species — kills microbes by inhibiting their cell membrane H+-ATPase pumps. Peptides containing this motif from six phylogenetically diverse sources (human lactoferrin, plus peptides from insects, plants, and fungi) all shared the same killing mechanism.
The common features included: cell death without breaking the membrane apart, loss of intracellular potassium through specific channels, dependence on cellular respiration, involvement of mitochondrial ATP synthase, and increases in intracellular ATP. These findings suggest the gamma-core motif is an ancient, universal antimicrobial weapon that has been conserved across kingdoms of life for billions of years.
Andrés, María T; Yount, Nannette Y; Acosta-Zaldívar, Maikel; Yeaman, Michael R; Fierro, José F · In Vitro
RPEP-07758 · 2024In 56 Sprague Dawley rats with lithium-pilocarpine-induced status epilepticus: Liraglutide reduced NLRP3 inflammasome pathway activation (↓NLRP3, Caspase-1, IL-1β) in hippocampal tissue. It activated the Nrf2 antioxidant pathway (↑Nrf-2, p-Nrf-2). Mitochondrial dynamics proteins were restored (Pink1, Mfn2, Drp1 normalized). Mitochondrial function in peripheral blood mononuclear cells was altered in both healthy and epileptic rats. Behavioral testing (open field, elevated plus maze, Morris water maze) showed liraglutide reversed the movement-enhancing effect of epilepsy.
Antmen, Fatma Merve; Fedaioglu, Zeynep; Acar, Dilan; Sayar, Ahmed Kerem; Yavuz, Ilayda Esma; Ada, Ece; Karakose, Bengisu; Rzayeva, Lale; Demircan, Sevcan; Kardouh, Farah; Senay, Simge; Kolgazi, Meltem; Suyen, Guldal; Oz-Arslan, Devrim ·
RPEP-07760 · 2024In the first real-world study of CGRP monoclonal antibody therapy from Thailand, 47 migraine patients (mostly using galcanezumab) showed strong responses over 6 months. At the 6-month mark, 89% had at least a 30% reduction in monthly migraine days, 71.6% achieved at least 50% reduction, and 58.5% achieved at least 70% reduction.
Monthly headache days decreased significantly over time (adjusted β = -0.42, p<0.001) and disability scores (MIDAS) also dropped significantly (adjusted β = -1.12, p=0.003). The response patterns were similar between patients with episodic migraine and chronic migraine, though episodic migraine patients had slightly higher response rates overall. Chronic migraine patients showed a steeper improvement trend in reducing abortive medication use.
Anukoolwittaya, Prakit; Hiransuthikul, Akarin; Pongpitakmetha, Thanakit; Thanprasertsuk, Sekh; Rattanawong, Wanakorn · Observational
RPEP-07766 · 2024Intranasal delivery of amino acid and peptide-based compounds can effectively reach the brain's monoamine systems (dopamine, serotonin, norepinephrine) by bypassing the blood-brain barrier through the nose-to-brain pathway. This review synthesizes experimental evidence showing that nasally administered peptides can modulate neurotransmitter systems relevant to psychiatric and neurodegenerative diseases.
The nose-to-brain route exploits direct neural connections (primarily the olfactory and trigeminal nerves) to transport peptide drugs from the nasal cavity to the central nervous system, avoiding both the blood-brain barrier and first-pass liver metabolism. The approach shows promise for conditions including schizophrenia, depression, anxiety, ADHD, Alzheimer's disease, and Parkinson's disease.
Apryatin, S; Moiseenko, V; Gainetdinov, R; Apryatina, V · Review
RPEP-07768 · 2024Adding salmon calcitonin (sCT, amylin receptor agonist) to ongoing dulaglutide (GLP-1R agonist) treatment reduced alcohol intake in both male and female rats without tolerance development. When sCT and dulaglutide were started simultaneously, an initial reduction in alcohol intake was observed in both sexes, but tolerance developed over time. Both treatment combinations consistently decreased food consumption and body weight in males and females. The treatment combination did not affect inflammatory mediators or receptor gene expression but did change fat tissue morphology.
Aranäs, Cajsa; Edvardsson, Christian E; Zentveld, Lindsay; Vallöf, Daniel; Witley, Sarah; Tufvesson-Alm, Maximilian; Shevchouk, Olesya T; Vestlund, Jesper; Jerlhag, Elisabet ·
RPEP-07769 · 2024Researchers deconstructed the peptide drug nerinetide — a neuroprotective agent for stroke and Alzheimer's disease — to understand the relationship between its plasma stability, ability to enter neurons, and therapeutic efficacy. Nerinetide combines a cell-penetrating peptide (CPP) sequence for neuronal delivery with a protein-protein interaction (PPI) inhibitory sequence that blocks harmful protein complex formation. The study provides design guidelines for creating next-generation peptide PPI inhibitors for neurodegenerative diseases.
Ariawan, Daryl; Thananthirige, Kanishka P M; El-Omar, Ali; van der Hoven, Julia; Genoud, Sian; Stefen, Holly; Fath, Thomas; van Eersel, Janet; Ittner, Lars M; Tietz, Ole ·
RPEP-07771 · 2024In the SURMOUNT-4 trial, adults with obesity who continued tirzepatide after an initial 36-week treatment period maintained and extended their weight loss, reaching a total reduction of 25.3% from baseline at 88 weeks. Those who switched to placebo regained most of their lost weight, ending with only 9.9% total weight reduction.
During the 36-week open-label lead-in, participants lost an average of 20.9% of their body weight on tirzepatide. After randomization, those who continued treatment lost an additional 5.5%, while those who switched to placebo regained 14.0% from their week-36 weight. A striking 89.5% of participants staying on tirzepatide kept at least 80% of their initial weight loss, compared to just 16.6% in the placebo group.
Aronne, Louis J; Sattar, Naveed; Horn, Deborah B; Bays, Harold E; Wharton, Sean; Lin, Wen-Yuan; Ahmad, Nadia N; Zhang, Shuyu; Liao, Ran; Bunck, Mathijs C; Jouravskaya, Irina; Murphy, Madhumita A · Randomized Controlled Trial
RPEP-07772 · 2024Extracellular vesicles (EVs) from VIP- and PACAP-stimulated macrophages produced three key effects in SARS-CoV-2-infected monocytes: (1) inhibited viral RNA synthesis and replication, (2) protected cells from virus-induced cytopathic effects, and (3) reduced production of pro-inflammatory mediators. The anti-inflammatory mechanism worked through prevention of SARS-CoV-2-induced NF-κB activation.
Two distinct EV subpopulations were identified based on morphology: large EVs (LEV) and small EVs (SEV), both isolated by differential centrifugation from macrophages cultured for 24 hours in serum-reduced conditions. These findings reveal that neuropeptide-stimulated macrophage EVs possess immunoregulatory properties that could contribute to both antiviral and anti-inflammatory responses during COVID-19.
Arteaga-Blanco, Luis A; Temerozo, Jairo R; Tiné, Lucas P S; Dantas-Pereira, Luíza; Sacramento, Carolina Q; Fintelman-Rodrigues, Natalia; Toja, Beatriz M; Gomes Dias, Suelen Silva; de Freitas, Caroline S; Espírito-Santo, Camila Couto; Silva, Ygor P; Frozza, Rudimar L; Bozza, Patrícia T; Menna-Barreto, Rubem F S; Souza, Thiago Moreno L; Bou-Habib, Dumith Chequer ·
RPEP-07782 · 2024The hypertonic saline test combined with plasma copeptin measurement has emerged as the diagnostic test with the highest accuracy for differentiating causes of polyuria-polydipsia syndrome, replacing the traditional water deprivation test as the gold standard.
Desmopressin, a synthetic AVP analogue specific for the AVP receptor 2 (AVPR2), remains the mainstay treatment and leads to rapid improvements in both excessive urination and excessive thirst. The main risk is dilutional hyponatraemia, which can be mitigated using the 'desmopressin escape method' — a dosing strategy that allows brief periods of breakthrough polyuria.
Additionally, recent evidence points to a concurrent oxytocin deficiency in patients with AVP deficiency, opening a new avenue for potential therapeutic intervention with oxytocin substitution.
Atila, Cihan; Refardt, Julie; Christ-Crain, Mirjam ·
RPEP-07784 · 2024Dulaglutide (a GLP-1 receptor agonist) completely restored testicular function in obese mice to normal levels. Obese mice had lower testes-to-body weight ratios, increased sperm DNA damage, chromosomal abnormalities, reduced sperm count and motility, more morphological defects, and disrupted testicular redox balance. Five weeks of dulaglutide treatment reversed all of these parameters back to control levels.
Importantly, dulaglutide showed no harmful effects on testicular cells when given to healthy, non-obese mice, suggesting safety for reproductive function.
Attia, Sabry M; Alshamrani, Ali A; Ahmad, Sheikh F; Albekairi, Norah A; Nadeem, Ahmed; Attia, Mohamed S M; Ansari, Mushtaq A; Alqahtani, Faleh; Bakheet, Saleh A; Harisa, Gamaleldin I · Animal
RPEP-07796 · 2024After propensity score matching (635 patients per group), semaglutide as adjunctive therapy showed significant improvements at 3 months:
- Visual disturbances: RR 0.28 (72% risk reduction, p=0.0001)
- Papilledema: RR 0.366 (63% risk reduction, p=0.0001)
- Headache: RR 0.578 (42% risk reduction, p=0.0001)
- Refractory disease: RR 0.60 (40% risk reduction, p=0.0001)
Benefits persisted through 24 months of follow-up. BMI showed progressive reduction, with a baseline-adjusted difference of -1.38 kg/m² at 24 months (p<0.0001). All comparisons were highly statistically significant.
Azzam, Ahmed Y; Essibayi, Muhammed Amir; Vaishnav, Dhrumil; Azab, Mohammed A; Morsy, Mahmoud M; Elamin, Osman; Zomia, Ahmed Saad Al; Alotaibi, Hammam A; Alamoud, Ahmed; Mohamed, Adham A; Ahmed, Omar S; Elswedy, Adam; Atallah, Oday; Abukhadijah, Hana J; Dmytriw, Adam A; Altschul, David J ·
RPEP-07799 · 2024The patient achieved a 40 kg weight loss (21% of body weight) and a BMI reduction from 49.66 to approximately 39.4 kg/m² over 6 months of dulaglutide treatment. This occurred despite multiple factors working against weight loss:
• Multiple antipsychotic medications for bipolar II disorder (known to cause weight gain)
• Non-compliance with lifestyle modifications
• Resistance to conventional treatment with metformin
• History as a professional sumo wrestler (extreme prior weight conditioning)
No side effects were reported, and glycemic control improved alongside the weight loss.
Bade, Sohail; Bade, Sahil; Sharma, Grishma; Bhurtel, Narayan; Singh, Yadvinder; Paudel, Sudip; Magar, Frena Pulami; Chapagain, Kshitij ·
RPEP-07800 · 2024Across 8 studies with 486 PCOS patients (ages 18-45, follow-up 12-32 weeks), GLP-1 receptor agonists consistently reduced BMI, waist circumference, fat mass, and visceral fat mass. Combined GLP-1 and metformin therapy produced greater reductions in these measurements compared to either treatment alone or other comparators.
GLP-1 agonists also improved some endocrine and metabolic parameters of PCOS, though the abstract notes the effects on these parameters "remain elusive" and vary across studies. The overall conclusion supports GLP-1 drugs as effective for weight reduction and metabolic improvement in PCOS, with combination therapy showing the most promise.
Bader, Salwa; Bhatti, Rahila; Mussa, Bashair; Abusanana, Salah · Systematic Review
RPEP-07802 · 2024A validated size-exclusion chromatography method (SEC-LC-UV/HRMS) was developed to detect and characterize aggregates in the GLP-1 peptide drug liraglutide under various stress conditions. Photolytic, thermal, freeze-thaw, and mechanical shaking stress all induced different levels of aggregation. The study also evaluated how common pharmaceutical excipients and surfactants affect liraglutide aggregation and stability over time, providing guidance for formulation development.
Badgujar, Devendra; Bawake, Sanket; Chawathe, Ashwini; Sharma, Nitish ·
RPEP-07805 · 2024The NPY-Nanoluc chimera accurately colocalized with endogenous dense core vesicle (DCV) markers in neurons, with minimal mislocalization to other cellular compartments. The reporter successfully detected DCV exocytosis in both rodent neurons and human neurons derived from induced pluripotent stem cells.
The assay showed the same calcium, RAB3, and STXBP1/MUNC18 dependence as established low-throughput methods, confirming its biological accuracy. It correctly reported modulation by known pharmacological agents (diacylglycerol analog and calcium channel blocker) and demonstrated higher sensitivity than the widely used single-cell low-throughput assay.
Baginska, Urszula; Balagura, Ganna; Toonen, Ruud F; Verhage, Matthijs ·
RPEP-07806 · 2024Botulinum neurotoxins (BoNTs) relieve neuropathic pain through multiple mechanisms that extend far beyond their well-known ability to block neurotransmitter release at the injection site. After peripheral injection, BoNTs are taken up by nerve terminals and reduce the release of pain signaling molecules — glutamate, CGRP, and substance P — decreasing neurogenic inflammation locally.
Critically, BoNTs are also retrogradely transported along nerve fibers to sensory ganglia and central nerve terminals, where they decrease expression of pain-promoting genes and reduce neurotransmitter release from central terminals. This likely reduces central sensitization in the spinal cord. The analgesic effect requires intact TRPV1-expressing pain fibers and substance P/neurokinin-1 receptor signaling.
Engineered BoNTs targeting specific nociceptive pathways are now being developed to improve safety and efficacy for chronic pain treatment.
Bagues, Ana; Hu, Jiaxin; Alshanqiti, Ishraq; Chung, Man-Kyo · Review
RPEP-07807 · 2024Bolespleenin334-347 demonstrated broad-spectrum antibacterial activity against both Gram-negative (A. baumannii) and Gram-positive (S. aureus) bacteria. Its mechanism involves dual action: disrupting bacterial membrane integrity causing cellular content leakage and inducing endogenous reactive oxygen species (ROS) accumulation within bacteria.
The peptide effectively inhibited biofilm formation by both A. baumannii and S. aureus, and critically, long-term treatment did not induce resistance development. Activity was maintained against clinically multidrug-resistant strains. Most impressively, in a mouse model of MRSA-induced superficial skin infection, Bolespleenin334-347 showed superior efficacy to both LL-37 and vancomycin, significantly reducing bacterial load and promoting better wound healing. The peptide also demonstrated good thermal stability and sodium ion tolerance.
Bai, Yuqi; Zhang, Weibin; Zheng, Wenbin; Meng, Xin-Zhan; Duan, Yingyi; Zhang, Chang; Chen, Fangyi; Wang, Ke-Jian ·
RPEP-07808 · 2024Semaglutide (available as weekly injection or daily pill) and tirzepatide (weekly injection targeting both GLP-1 and GIP receptors) have achieved HbA1c reductions of over 2% and body weight reductions of over 10% in type 2 diabetes patients. In non-diabetic obese individuals treated at higher doses, weight loss exceeded 15%.
Emerging evidence shows cardio-protective and potentially reno-protective effects. Next-generation therapies in early clinical development — retatrutide (triple GLP-1/GIP/glucagon agonist) and CagriSema (semaglutide + amylin analogue cagrilintide) — have demonstrated even stronger efficacy. Gastrointestinal side effects are generally mild-to-moderate and transient, though they cause some patients to discontinue treatment.
Bailey, Clifford J; Flatt, Peter R; Conlon, J Michael ·
RPEP-07813 · 2024In 23 adolescents and young adults (ages 12-21) with treatment-resistant migraines:
- 91.3% experienced reduced migraine duration and intensity
- 82.6% reported improvements in other bothersome symptoms
- 73.9% had improved response to rescue medications
- 78.3% reduced rescue medication use by more than 50%
- 56.5% had fewer emergency room visits
- 82.6% had significant headache day reductions at 1 month, 87% at 3 months
- Nearly 40% had >50% reduction in headache days at both timepoints
- 95.7% reported no side effects
- 69.6% chose to continue treatment
Greatest benefits were in patients treated for >6 months. Most patients (78.3%) had chronic migraine.
Bandatmakur, Anjaneya Shankar Madhav; Dave, Pooja; Kerr, Melissa; Brunick, Colin; Wen, Sijin; Hansen, Nicholas ·
RPEP-07814 · 2024Researchers developed a two-part innovation for cancer vaccines: a new computational algorithm (NOAH) that selects neoantigen peptides based on how they interact with both MHC molecules and T cell receptors (not just MHC binding alone), and an engineered virus-like particle (VLP) platform based on HIV-1 Gag that displays high copy numbers of these selected neoantigens. In a mouse melanoma model, VLPs loaded with neoantigens selected for enhanced TCR interaction generated new anti-tumor immune responses and delayed tumor growth. The study demonstrates that incorporating TCR interaction into neoantigen selection improves the immunogenicity of peptide cancer vaccines.
Barajas, Ana; Amengual-Rigo, Pep; Pons-Grífols, Anna; Ortiz, Raquel; Gracia Carmona, Oriol; Urrea, Victor; de la Iglesia, Nuria; Blanco-Heredia, Juan; Anjos-Souza, Carla; Varela, Ismael; Trinité, Benjamin; Tarrés-Freixas, Ferran; Rovirosa, Carla; Lepore, Rosalba; Vázquez, Miguel; de Mattos-Arruda, Leticia; Valencia, Alfonso; Clotet, Bonaventura; Aguilar-Gurrieri, Carmen; Guallar, Victor; Carrillo, Jorge; Blanco, Julià · Animal Study
RPEP-07817 · 2024Atogepant is a second-generation CGRP receptor antagonist (gepant) that represents a significant advance in migraine prevention. It works by competitively blocking CGRP receptors, inhibiting trigeminovascular nociception — the pathway directly implicated in migraine pain.
A key advantage over first-generation gepants is its improved safety profile, specifically a reduced risk of liver injury, which was a major limitation of earlier drugs in the class. Atogepant has been approved for the prevention of both episodic and chronic migraine in adults, supported by phase I, II, and III clinical trial data.
Baraldi, Carlo; Beier, Dagmar; Martelletti, Paolo; Pellesi, Lanfranco · Review
RPEP-07818 · 2024Across 6 RCTs (28,762 patients) and 2 observational studies:
- Semaglutide group: 14,608 subjects
- Control/placebo group: 14,716 subjects
- Heart failure risk: OR 0.74 (95% CI: 0.58-0.94) — a 26% reduction
- Heterogeneity: I² = 45% (moderate)
- No evidence of publication bias
- Sensitivity analysis confirmed robust results
Barbagelata, Leandro; Masson, Walter; Lobo, Martín; Bluro, Ignacio ·
RPEP-07825 · 2024The review resolves conflicting findings about the NPY Y2 receptor by proposing a G protein switch model. In the normal state, blocking Y2 receptors (with BIIE0246) causes pain and hypersensitivity. After nerve injury or inflammation, the same Y2 blocker paradoxically reduces mechanical and thermal hypersensitivity and improves the emotional dimension of pain. In chronic pain models of latent sensitization, Y2 blockade causes a profound return of pain-like behaviors. This suggests Y2 signaling switches from antinociception (normal) to anti-hyperalgesia (injured) and back to antinociception (remission).
Basu, Paramita; Taylor, Bradley K ·
RPEP-07827 · 2024In 637 neuroendocrine tumor patients, extending peptide receptor radionuclide therapy (PRRT) beyond the standard 4 cycles was safe and improved survival. The extended treatment group (>4 cycles, n=356) had significantly longer median overall survival (72.8 months) compared to the standard group (4 cycles, n=281, 52.8 months). Cox regression confirmed a 42% lower risk of death (HR 0.580, p<0.001) and 40% lower disease-specific mortality (HR 0.599, p<0.001) in the extended group. Kidney safety was comparable: mean post-treatment creatinine levels did not differ significantly (93.20 vs 89.30 μmol/L, p=0.364), and adverse renal events occurred in only 1.1% of extended vs 0.4% of standard patients.
Baum, Richard P; Fan, Xin; Jakobsson, Vivianne; Schuchardt, Christiane; Chen, Xiaoyuan; Yu, Fei; Zhang, Jingjing ·