RPEP-03961 · 2018Three new antimicrobial peptides based on the RRWQWR motif from bovine lactoferricin B were designed as linear, dimeric, and tetrameric variants. All three outperformed the reference peptide against both ATCC reference strains and clinical isolates of Gram-positive and Gram-negative bacteria. MIC50 values ranged from 1.6-198.0 μM across different bacteria. However, the tetrameric peptide showed strong hemolytic activity (49.1% at 100 μM), limiting its therapeutic potential. SEM imaging confirmed that the branched designs expose the RRWQWR motif to pathogen surfaces.
Vega, Sandra C; Martínez, Diana A; Chalá, María Del S; Vargas, Hernán A; Rosas, Jaiver E ·
RPEP-03966 · 2018BPC 157 administered at doses of 10 μg or 10 ng/kg counteracted virtually all consequences of inferior caval vein ligation in rats. Direct vein injury, thrombosis, thrombocytopenia, and prolonged bleeding were all counteracted. The peptide promoted rapid formation of collateral blood vessels and redistribution of trapped blood volume through alternative venous pathways.
Hemodynamic disturbances including venous hypertension, arterial hypotension, and tachycardia were counteracted. BPC 157-treated rats showed raised plasma nitric oxide values but normal MDA (oxidative stress marker) values. In vein tissue, the peptide reversed low NO values and counteracted elevated MDA levels. Gene expression changes were observed in EGR, NOS, SRF, VEGFR, and KRAS across multiple veins.
Vukojević, Jakša; Siroglavić, Marko; Kašnik, Katarina; Kralj, Tamara; Stanćić, Duje; Kokot, Antonio; Kolarić, Darko; Drmić, Domagoj; Sever, Anita Zenko; Barišić, Ivan; Šuran, Jelena; Bojić, Davor; Patrlj, Masa Hrelec; Sjekavica, Ivica; Pavlov, Katarina Horvat; Vidović, Tinka; Vlainić, Josipa; Stupnišek, Mirjana; Seiwerth, Sven; Sikirić, Predrag ·
RPEP-03967 · 2018Lunasin, a peptide naturally found in soybeans, has demonstrated both cancer-preventive (chemopreventive) and cancer-fighting (therapeutic) properties against multiple cancer types in preclinical studies. What makes lunasin unique is that it contains multiple functional domains that work through two distinct mechanisms: modifying gene expression by affecting histone acetylation (epigenetic regulation) and disrupting integrin signaling in cancer cells.
Recent studies highlighted in this review show that lunasin's effects on integrin signaling in cancer stem cells are particularly noteworthy — it reduces the expression of stemness factors, which are the genes that allow cancer stem cells to maintain their aggressive, self-renewing properties. This leads to a reduction in metastatic potential, meaning the cancer becomes less likely to spread. The peptide's dual mechanism of action through both epigenetic and cell signaling pathways sets it apart from most single-target anticancer agents.
Vuyyuri, Saleha B; Shidal, Chris; Davis, Keith R · Review
RPEP-03968 · 2018Selank acts as a positive allosteric modulator of GABA receptors, enhancing GABA binding in a concentration-dependent and subtype-selective manner. When combined with benzodiazepines like diazepam or the antipsychotic olanzapine, Selank's effects were not additive — instead, it blocked the modulatory activity of these drugs.
This indicates that Selank's binding site on the GABA receptor is distinct from the benzodiazepine binding site, though the sites may partially overlap. The non-cumulative interaction pattern suggests Selank modulates GABA signaling through a fundamentally different mechanism than conventional anxiolytics.
Vyunova, Tatiana V; Andreeva, Lioudmila; Shevchenko, Konstantin; Myasoedov, Nikolay ·
RPEP-03969 · 2018The review examined both genetic and environmental animal models of ASD in which the oxytocin system was investigated. Key findings include evidence that the oxytocin system is perturbed in specific animal models of ASD, and that oxytocin administration can improve ASD-associated social behavior deficits in some of these models.
Critically, the authors highlight that not all ASD subtypes involve oxytocin system disruption, and that the enormous heterogeneity of ASD may explain why clinical trials of oxytocin in humans have produced mixed results. They argue that perturbations in the oxytocin system should be investigated as potential stratifying biomarkers to identify which individuals are most likely to benefit from oxytocin treatment.
Wagner, Shlomo; Harony-Nicolas, Hala ·
RPEP-03972 · 2018A modified version of thymosin alpha-1 (Tα1) fused with the tumor-homing peptide iRGD showed stronger antitumor activity than standard Tα1 against both melanoma and lung cancer in mice. The fusion peptide Tα1-iRGD promoted T-cell activation and increased CD86 expression on immune cells, accumulated more effectively in tumors, reduced tumor blood vessel density, and attached more readily to B16F10 melanoma and H460 lung cancer cells.
The modified peptide also demonstrated significantly better immunomodulatory activity in hydrocortisone-induced immunosuppression models, suggesting enhanced ability to boost immune function even under immunosuppressive conditions.
Wang, Fanwen; Li, Bin; Fu, Pengcheng; Li, Qingqing; Zheng, Heng; Lao, Xingzhen ·
RPEP-03973 · 2018The Tα1-Fc fusion protein achieved a serum half-life of 25 hours in mice — approximately 13 times longer than native Tα1. Production yielded approximately 160.4 mg/L at greater than 90.3% purity. In tumor models, Tα1-Fc showed stronger antitumor activity than Tα1 in both 4T1 (breast cancer) and B16F10 (melanoma) xenograft models. The mechanism involved upregulation of CD86 expression (dendritic cell activation), increased secretion of IFN-γ and IL-2 (immune cytokines), and greater tumor infiltration by CD4+ and CD8+ T cells. The fusion protein also showed stronger activity in repairing immune injury by increasing lymphocyte counts.
Wang, Fanwen; Yu, Tingting; Zheng, Heng; Lao, Xingzhen ·
RPEP-03976 · 2018The lipid-modified cell-penetrating peptide micelles achieved multiple functional goals: they self-assembled to co-load both narciclasine (an AMPK activator) and siULK1 (an autophagy-blocking siRNA), showed pH-sensitive drug release favoring the acidic tumor microenvironment, and facilitated cellular uptake and endosome escape in HepG2 liver cancer cells.
In vitro, the combination treatment significantly increased apoptosis (programmed cell death) while declining autophagy through targeted regulation of the AMPK-ULK1 signaling axis. In vivo, the micelles efficiently reduced tumor growth in HCC xenograft models in mice with good safety profiles, confirming that simultaneously blocking autophagy while promoting cell death creates a synergistic anti-cancer effect.
Wang, Xiaoyun; Wu, Fengbo; Li, Guoyou; Zhang, Nan; Song, Xiangrong; Zheng, Yu; Gong, Changyang; Han, Bo; He, Gu ·
RPEP-03979 · 2018The researchers discovered that a cyclobutane-1,1-dicarboxamide-containing linker is hydrolyzed predominantly by cathepsin B, unlike the standard valine-citrulline dipeptide linker which is cleaved by multiple proteases. Key results:
• The novel peptidomimetic linker showed enhanced protease specificity — preferentially cleaved by cathepsin B rather than multiple lysosomal enzymes
• ADCs with the new linker were equally efficacious in vivo as those with the standard valine-citrulline dipeptide linker
• Serum stability was maintained — the new linker did not break down prematurely in blood
• Structure-guided design using crystallography informed the linker optimization
• The approach opens a new chemical space beyond peptide-based linkers for controlling drug release selectivity
Wei, BinQing; Gunzner-Toste, Janet; Yao, Hui; Wang, Tao; Wang, Jing; Xu, Zijin; Chen, Jinhua; Wai, John; Nonomiya, Jim; Tsai, Siao Ping; Chuh, Josefa; Kozak, Katherine R; Liu, Yichin; Yu, Shang-Fan; Lau, Jeff; Li, Guangmin; Phillips, Gail D; Leipold, Doug; Kamath, Amrita; Su, Dian; Xu, Keyang; Eigenbrot, Charles; Steinbacher, Stefan; Ohri, Rachana; Raab, Helga; Staben, Leanna R; Zhao, Guiling; Flygare, John A; Pillow, Thomas H; Verma, Vishal; Masterson, Luke A; Howard, Philip W; Safina, Brian ·
RPEP-03983 · 2018Researchers identified a gene (vanZ1/CD1240) in C. difficile that contributes to low-level resistance against the antibiotic teicoplanin. When this gene was deleted, the bacteria became moderately more susceptible to teicoplanin. Restoring the gene restored resistance.
An unexpected finding: the antimicrobial peptide LL-37 (a human cathelicidin) triggered increased expression of the vanZ1 gene, even though VanZ1 itself didn't protect against LL-37. This suggests the bacterium may be using LL-37 as an environmental signal — detecting the human immune response and upregulating resistance factors in anticipation of antibiotic exposure.
The vanZ1 gene sits within a genetic element (the skin element) that is cut out during sporulation, meaning it is only active in vegetatively growing cells, not spores.
Woods, Emily C; Wetzel, Daniela; Mukerjee, Monjori; McBride, Shonna M · Laboratory Study
RPEP-03984 · 2018The review presents three key lines of evidence that gut peptide satiation is learned rather than innate. First, the ability of some GI peptides to modify food intake depends on past experience and can be changed with new experience (malleable). Second, CCK and other 'satiation' signals that reduce food intake acutely may not continue to do so over repeated trials. Third, individuals only respond to a particular signal so long as it provides reliable information about caloric content.
When a gut peptide becomes an unreliable predictor of calories (as happens with repeated exogenous administration), the individual shifts to relying on other signals to end meals. This learned association model explains why genetic knockouts and chronic peptide administration fail to produce sustained weight loss — the system compensates by using alternative satiety cues.
Woods, Stephen C; May-Zhang, Aaron A; Begg, Denovan P ·
RPEP-03996 · 2018Macroporous silica nanoparticles with thiol surface modification achieved over 40% Bcl-2-converting peptide loading efficiency. The peptide penetrated into drug-resistant MCF7/DOX breast cancer cell mitochondria and bound Bcl-2, exposing its BH3 domain to convert it from pro-survival to pro-apoptotic. Different surface functionalities affected efficacy: amine-modified MSN surfaces caused the greatest cell apoptosis-inducing effect. This is the first demonstration of pore size and surface functionality-modulated silica nanoparticles for delivery of bio-macromolecules to treat multidrug resistant cancer.
Xu, Weixia; Ge, Pengjin; Niu, Boning; Zhang, Xiaokun; Liu, Jie; Xie, Jingjing ·
RPEP-04001 · 2018This is a study protocol, not a results paper. The planned trial will randomize 90 prediabetic and/or overweight smokers 1:1 to exenatide extended-release or placebo, both combined with transdermal nicotine replacement therapy (NRT) and behavioral counseling.
Outcomes include smoking abstinence (verified by expired CO ≤5 ppm), craving (Questionnaire of Smoking Urges), and withdrawal symptoms (Wisconsin Scale), assessed weekly during 6 weeks of treatment and at 1 and 4 weeks post-treatment. Cue-induced craving will be measured using virtual reality exposure at baseline and 3 weeks. The hypothesis is that exenatide will increase complete abstinence rates and reduce craving and withdrawal above standard NRT alone.
Yammine, Luba; Kosten, Thomas R; Cinciripini, Paul M; Green, Charles E; Meininger, Janet C; Minnix, Jennifer A; Newton, Thomas F ·
RPEP-04003 · 2018Current infection prevention strategies for severe acute pancreatitis achieve limited success, likely because they fail to address the underlying immunosuppression that triggers infection. Thymosin α1, which has immune-cell-regulating properties, showed a prophylactic effect against SAP-related infection in clinical studies.
The review highlights that the immune suppression occurring in SAP's late phase is a key driver of infection risk, and that immunomodulatory therapies like thymosin α1 target this root cause rather than just treating infections after they occur. However, the evidence base remains at an early stage with limited sample sizes.
Yang, Na; Ke, Lu; Tong, Zhihui; Li, Weiqin ·
RPEP-04005 · 2018Patients with Fabry disease showed significantly elevated levels of multiple inflammatory and cardiac remodeling biomarkers compared to healthy controls, including the natriuretic peptides BNP and MR-pro ANP, matrix metalloproteases (MMP-2, MMP-9), TNF, TNFR1, TNFR2, IL-6, galectin-1, and globotriaosylsphingosine.
Key biomarker correlations included: TNFR2, TNF, IL-6, MMP-2, and globotriaosylsphingosine were elevated in patients with left ventricular hypertrophy; BNP, MR-pro ANP, and MMP-2 correlated with diastolic dysfunction; and patients with cardiac scarring (late gadolinium enhancement on MRI) had higher BNP, MR-pro ANP, TNFR1, TNFR2, and MMP-2. These findings support a phenotype dominated by heart failure with preserved ejection fraction driven by systemic inflammation.
Yogasundaram, Haran; Nikhanj, Anish; Putko, Brendan N; Boutin, Michel; Jain-Ghai, Shailly; Khan, Aneal; Auray-Blais, Christiane; West, Michael L; Oudit, Gavin Y · Observational
RPEP-04006 · 2018Collagen hydrolysate (CH) — the collagen peptides found in supplements — increased procollagen I and collagen I content in human skin fibroblasts through a two-pronged mechanism: stimulating new collagen production while simultaneously inhibiting the enzymes (MMP-1 and MMP-2) that break collagen down. This worked in both standard cell cultures and a more realistic 3D human dermal equivalent model.
Importantly, the effects were consistent regardless of whether fibroblasts came from sun-protected (chronologically aged) or sun-exposed (photoaged) skin. However, sun-exposed fibroblasts appeared more responsive — lower concentrations of collagen peptides were sufficient to stimulate them, suggesting photoaged skin cells may be more sensitive to the treatment.
Zague, Vivian; do Amaral, Jonatas Bussador; Rezende Teixeira, Paula; de Oliveira Niero, Evandro Luis; Lauand, Camila; Machado-Santelli, Glaucia Maria · In Vitro
RPEP-04009 · 2018Peptidomimetics — particularly stapled peptides and macrocyclic peptides — have been successfully applied to target numerous 'undruggable' protein-protein interactions, combining the targeting capability of peptides with improved pharmacokinetic properties through conformational constraint.
Zhang, Gan; Andersen, Jessica; Gerona-Navarro, Guillermo ·
RPEP-04011 · 2018In capsaicin-induced cough guinea pig model (N=10 per group, 4 groups):
- Both inhaled and oral SB705498 significantly reduced cough numbers (p<0.001) and prolonged cough incubation periods (p<0.001) compared to saline control
- Codeine (positive control) also significantly reduced coughing
- SB705498 reduced expression of three neuropeptides in lung and brain tissue (all p<0.05): substance P (SP), calcitonin gene-related peptide (CGRP), and neurokinin A (NKA)
- No lung or brain parenchymal inflammation was observed in any group (safety signal)
- Both routes of SB705498 administration (inhaled and oral) were effective
Zhang, Li; Sun, Tieying; Liu, Longteng; Wang, Lifang ·
RPEP-04012 · 2018Dispersion-stable LDH nanoparticles were significantly more effective than aggregated ones, demonstrating that colloidal stability is a critical factor for vaccine efficacy. The well-dispersed formulation induced stronger cytotoxic T-lymphocyte (CTL) responses and significantly better tumor growth inhibition.
A multi-target vaccine co-loading three peptide epitopes (Trp2, M27, and M30 mutated epitopes) with CpG adjuvant onto dispersion-stable LDH nanoparticles showed remarkable melanoma growth inhibition — superior to single-antigen approaches. This demonstrates that LDH nanoparticles can serve as an effective multi-antigen delivery platform for personalized cancer immunotherapy.
Zhang, Ling-Xiao; Xie, Xi-Xiu; Liu, Dong-Qun; Xu, Zhi Ping; Liu, Rui-Tian ·
RPEP-04014 · 2018Exendin-4 reduced TNF-α secretion from sham (healthy) monocytes but unexpectedly increased it from burn monocytes. This reversal was caused by a switch in GLP-1 receptor signaling: burn monocytes showed reduced Gαs expression and increased Gαi expression compared to sham cells. Blocking Gαi signaling with pertussis toxin reversed the pro-inflammatory effect. In burn monocytes, Exendin-4 failed to stimulate cAMP production (the normal anti-inflammatory pathway) and instead activated ERK1/2 and NF-κB pro-inflammatory pathways.
Zhang, Qing-Hong; Hao, Ji-Wei; Li, Guang-Lei; Ji, Xiao-Jing; Yao, Xu-Dong; Dong, Ning; Yao, Yong-Ming ·
RPEP-04018 · 2018The mitochondria-targeted peptide SS-31 (elamipretide) provided significant neuroprotection after traumatic brain injury in mice when administered 30 minutes post-injury. SS-31 reversed mitochondrial dysfunction by reducing reactive oxygen species, restoring superoxide dismutase activity, decreasing oxidative damage markers (MDA), and preventing cytochrome c release.
This translated to reduced neurological deficits, brain swelling, DNA damage, and neural cell death. Mechanistically, SS-31 restored SIRT1 expression and promoted PGC-1α nuclear translocation, suggesting it enhanced mitochondrial biogenesis — the creation of new, healthy mitochondria to replace damaged ones.
Zhu, Yihao; Wang, Handong; Fang, Jiang; Dai, Wei; Zhou, Jiang; Wang, Xiaoliang; Zhou, Mengliang · Animal
RPEP-04021 · 2018Across 22 studies reviewed, MR-proADM demonstrated strong utility as a biomarker for both diagnosing sepsis and predicting outcomes in septic shock patients. Its prognostic accuracy improved during patient follow-up, with area under the curve (AUC) values exceeding 0.8 for mortality prediction in several studies.
The biomarker's performance was enhanced when combined with other biomarkers or clinical severity scores, and it showed particularly strong correlation with the degree of organ failure. MR-proADM also showed potential value in specific subpopulations, including sepsis patients with burns or malignant tumors.
Önal, Uğur; Valenzuela-Sánchez, Francisco; Vandana, Kalwaje Eshwara; Rello, Jordi ·
RPEP-04032 · 2019LyeTxI-b, a cationic alpha-helical antimicrobial peptide, showed potent cytotoxicity against U87-MG glioblastoma cells through a membranolytic mechanism. Membrane disruption occurred within 15 minutes, confirmed by trypan blue uptake, reduced calcein-AM conversion, and LDH release. Scanning electron microscopy revealed physical holes and pores in the cancer cell membranes.
Imaging flow cytometry confirmed that 59% of cells underwent necroptosis after 3 hours of treatment. Necrostatin-1 (a necroptosis inhibitor) partially protected cells in a dose-dependent manner, confirming the necroptosis pathway. Transmission electron microscopy showed swollen nuclei, vacuolized organelles, and electron-lucent cytoplasm. Importantly, the peptide showed only mild cytotoxicity against normal human and monkey fibroblasts and low hemolytic activity.
Abdel-Salam, Mostafa A L; Carvalho-Tavares, Juliana; Gomes, Kamila Sousa; Teixeira-Carvalho, Andrea; Kitten, Gregory T; Nyffeler, Johanna; Dias, Felipe F; Dos Reis, Pablo V Mendes; Pimenta, Adriano M C; Leist, Marcel; de Lima, Maria Elena; de Souza-Fagundes, Elaine Maria ·
RPEP-04034 · 2019Researchers used a 'mirror image phage display' technique to discover short peptide antibiotics made entirely of D-amino acids (the mirror image of natural L-amino acids). These peptides — in linear, cyclic, and bicyclic forms — killed Staphylococcus aureus, MRSA, and vancomycin-resistant Enterococci (VRE) with moderately high antibacterial activity. Crucially, they showed no toxicity to human red blood cells or mammalian cells at active concentrations.
Because D-amino acid peptides are not recognized by the body's protein-degrading enzymes, they are metabolically stable and could potentially be delivered orally — a major advantage over natural peptide antibiotics that are quickly destroyed in the gut.
Adaligil, Emel; Patil, Kalyani; Rodenstein, Marissa; Kumar, Krishna · Basic Research
RPEP-04037 · 2019Chloroquine-TP10 conjugates showed higher antiplasmodial activity than the parent TP10 peptide alone. However, both chloroquine-TP10 and primaquine-TP10 conjugates exhibited strong hemolytic activity — they bound to and destroyed red blood cell membranes, as demonstrated by fluorescence microscopy and flow cytometry.
This is a critical negative finding: despite cell-penetrating peptides being widely reported as safe and effective carriers for diverse cargoes (from small drugs to large biomolecules), coupling them to aminoquinoline antimalarials specifically produces unacceptable hemolysis. The authors conclude that cell-penetrating peptides are unsuitable for safe intracellular delivery of this drug class and urge researchers to systematically assess hemolytic effects in all peptide-drug conjugate development.
Aguiar, Luísa; Biosca, Arnau; Lantero, Elena; Gut, Jiri; Vale, Nuno; Rosenthal, Philip J; Nogueira, Fátima; Andreu, David; Fernàndez-Busquets, Xavier; Gomes, Paula ·
RPEP-04040 · 2019An independent expert panel reviewed all suspected pancreatitis cases across the entire HARMONY Phase III clinical program for albiglutide (a GLP-1 receptor agonist). Of 4,895 patients studied, 43 had potential pancreatitis cases, of which 11 were adjudicated as definite or probable acute pancreatitis (8 on albiglutide, 3 on active comparators). The pancreatitis rate with albiglutide was 0.3% (6/2,365) compared to 0% with placebo (0/486) and 0.08% with non-GLP-1RA active comparators (2/2,062 — but both confirmed cases in the comparator group were actually in patients receiving a different GLP-1RA).
While pancreatitis was uncommon overall, the rate was numerically higher with albiglutide than placebo, and the independent committee judged most cases as at least possibly related to the drug.
Al-Kawas, Firas; Anderson, Michelle Ann; Enns, Robert; Wilson, Timothy H; Johnson, Susan; Mallory, Jason M · Post Hoc Analysis
RPEP-04043 · 2019Two probiotic bacteria (L. helveticus LH-2 and L. acidophilus La-5) fermenting whey protein produced unique peptide profiles. Unfermented whey contained 109 milk-derived peptides, 39 of which had known bioactivities (ACE inhibitory, antioxidant, antimicrobial, immunomodulating). Fermentation dramatically reshaped this profile — LH-2 produced 75 peptides and La-5 produced 15.
The fermented peptide mixtures downregulated virulence genes (hilA and ssrB) in Salmonella Typhimurium, reducing its ability to cause disease. Crucially, when Salmonella's peptide transporter (oppA) was knocked out, this anti-virulence effect disappeared — suggesting Salmonella must actively import these peptides for them to suppress virulence.
This means probiotic fermentation of whey creates bioactive peptides that can directly disarm a dangerous pathogen by getting inside it.
Ali, Eman; Nielsen, Søren D; Abd-El Aal, Salah; El-Leboudy, Ahlam; Saleh, Ebeed; LaPointe, Gisèle · Laboratory Study
RPEP-04046 · 2019For the bremelanotide 1.75 mg dose in the overall modified intention-to-treat population:
- All 7 endpoints achieved statistical significance vs. placebo (p ≤ 0.03)
- Endpoints included: FSFI-desire domain, FSDS-DAO total score, FSDS-DAO items 13 and 14, and number of satisfying sexual events
- Minimal clinically important differences (MCIDs) determined by ROC curves matched expert clinical estimates
- The drug was safe and well tolerated
- These responder definitions were used in the subsequent Phase 3 RECONNECT registration trials
Multiple responder analysis methods (historical anchors, self-reported global benefit, ROC curves, cumulative distribution) converged on the same conclusions, strengthening confidence in the clinical meaningfulness of the improvements.
Althof, Stanley; Derogatis, Leonard R; Greenberg, Sally; Clayton, Anita H; Jordan, Robert; Lucas, Johna; Spana, Carl ·
RPEP-04055 · 2019Most Japanese daily dishes contain 0.2-2.5 g of collagen per meat serving, with collagen-rich foods (beef tendon, eel with skin, skinned shark tail) containing 7.6-13.3 g. After ingesting cooked shark meat, nine collagen di- and tripeptides were detected in plasma. The area under the curve for most peptides was approximately 30% of that after ingesting collagen hydrolysate with an equivalent collagen amount (except Hyp-Gly and Pro-Hyp-Gly). In vitro digestion with pepsin and pancreatin liberated only ~30% of total meat collagen into solution, explaining the lower bioavailability from whole food.
Asai, Tomoko; Takahashi, Akira; Ito, Kumie; Uetake, Tatsuo; Matsumura, Yasuki; Ikeda, Kaori; Inagaki, Nobuya; Nakata, Masahiro; Imanishi, Yoshiharu; Sato, Kenji ·
RPEP-04058 · 2019In 60 Parkinson's patients from the Exenatide-PD trial, neuron-derived exosomes revealed:
- Exenatide significantly increased tyrosine phosphorylation of insulin receptor substrate 1 at 48 weeks (p=0.003) and 60 weeks (p=0.01)
- Total Akt expression was elevated in the exenatide group (p<0.001)
- Phosphorylated mTOR was increased (p=0.02)
- Motor function improvements (MDS-UPDRS Part 3 scores) correlated significantly with total mTOR levels (p=0.001) and phosphorylated mTOR levels (p=0.04)
These changes persisted even 12 weeks after stopping the drug (60-week timepoint), suggesting sustained neuroprotective effects rather than just symptomatic relief.
Athauda, Dilan; Gulyani, Seema; Karnati, Hanuma Kumar; Li, Yazhou; Tweedie, David; Mustapic, Maja; Chawla, Sahil; Chowdhury, Kashfia; Skene, Simon S; Greig, Nigel H; Kapogiannis, Dimitrios; Foltynie, Thomas ·
RPEP-04062 · 2019Among 14,752 EXSCEL participants, 2,800 (19%) had PAD at baseline. PAD patients versus non-PAD patients had:
- Higher MACE rates: 13.6% vs 11.4% (adjusted HR 1.13, 95% CI 1.00-1.27, P=0.047)
- Higher all-cause mortality: adjusted HR 1.38 (95% CI 1.20-1.60, P<0.001)
- Higher LEA rates
Exenatide versus placebo showed no differences in MACE or lower-extremity amputation rates, regardless of PAD status. This means exenatide was neither beneficial nor harmful in this high-risk population.
Badjatiya, Anish; Merrill, Peter; Buse, John B; Goodman, Shaun G; Katona, Brian; Iqbal, Nayyar; Pagidipati, Neha J; Sattar, Naveed; Holman, Rury R; Hernandez, Adrian F; Mentz, Robert J; Patel, Manesh R; Jones, W Schuyler ·
RPEP-04064 · 2019This review of major cardiovascular outcome trials found that GLP-1 receptor agonists (liraglutide in the LEADER trial, semaglutide in the SUSTAIN-6 trial) significantly reduced major adverse cardiac events (MACE) in people with type 2 diabetes. SGLT2 inhibitors (empagliflozin in EMPA-REG OUTCOME, canagliflozin in CANVAS) also significantly reduced MACE and hospitalizations for heart failure. DPP-4 inhibitors showed cardiovascular neutrality — they neither increased nor decreased MACE — though a small increased risk of heart failure with some members of the class could not be ruled out.
Importantly, the review notes that most trial participants had already experienced cardiovascular events, meaning these results primarily reflect secondary prevention. The majority of people with type 2 diabetes who take these medications have not had prior cardiovascular events, so how these benefits translate to primary prevention remains an open question.
Bailey, Clifford J; Marx, Nikolaus · Review
RPEP-04065 · 2019VIP knockout mice (VIP-/-) showed significant changes in gut bacterial composition, reduced biodiversity, and weight loss compared to wild-type (VIP+/+) and heterozygous (VIP+/-) littermates, regardless of sex. The altered microbiome profile in VIP-deficient mice resembled microbial changes reported in inflammatory and autoimmune disorders. Predictive functional analysis using PICRUSt software suggested an energy surplus within the altered microbiota, indicating shifts in bacterial metabolic function. These effects were consistent across 47 mice of both sexes.
Bains, Manpreet; Laney, Caleb; Wolfe, Annie E; Orr, Megan; Waschek, James A; Ericsson, Aaron C; Dorsam, Glenn P ·
RPEP-04071 · 2019The fluorescent LEAP2 analogue (F-LEAP2) displayed binding affinity and inverse agonism to GHSR similar to native LEAP2. Notably, F-LEAP2 labeled GHSR on the cell surface, while fluorescent ghrelin was mainly observed inside cells — revealing different receptor trafficking patterns for agonists versus antagonists.
When centrally injected in mice, F-LEAP2 reduced ghrelin-induced food intake with efficacy similar to native LEAP2 and specifically labeled cells in GHSR-expressing brain areas. This dual functionality — biological activity plus fluorescent visualization — makes F-LEAP2 a uniquely valuable research tool.
Barrile, Franco; M'Kadmi, Céline; De Francesco, Pablo N; Cabral, Agustina; García Romero, Guadalupe; Mustafá, Emilio R; Cantel, Sonia; Damian, Marjorie; Mary, Sophie; Denoyelle, Séverine; Banères, Jean-Louis; Marie, Jacky; Raingo, Jesica; Fehrentz, Jean-Alain; Perelló, Mario ·
RPEP-04075 · 2019Four weeks of subcutaneous GOP infusion produced significantly greater weight loss than placebo (-4.4 kg vs -2.5 kg, p=0.025) and substantially greater improvement in fructosamine levels (-44.1 vs -11.7 µmol/L, p=0.0026), a marker of medium-term blood sugar control.
The most striking finding was the comparison with gastric bypass (RYGB) and very low-calorie diet (VLCD). Despite causing less total weight loss than either comparator, GOP achieved superior glucose tolerance after a mixed meal and reduced glycemic variability on continuous glucose monitoring. This suggests the three-hormone combination has direct glucose-regulating effects independent of weight loss alone.
Behary, Preeshila; Tharakan, George; Alexiadou, Kleopatra; Johnson, Nicholas; Wewer Albrechtsen, Nicolai J; Kenkre, Julia; Cuenco, Joyceline; Hope, David; Anyiam, Oluwaseun; Choudhury, Sirazum; Alessimii, Haya; Poddar, Ankur; Minnion, James; Doyle, Chedie; Frost, Gary; Le Roux, Carel; Purkayastha, Sanjay; Moorthy, Krishna; Dhillo, Waljit; Holst, Jens J; Ahmed, Ahmed R; Prevost, A Toby; Bloom, Stephen R; Tan, Tricia M ·
RPEP-04076 · 2019Researchers developed a systematic bioinformatics workflow for selecting optimal cell-penetrating peptides (CPPs) for covalent conjugation to therapeutic proteins. From 1,155 CPPs, 70 with the highest predicted uptake efficiency were screened. N-terminal conjugation produced significantly higher-quality constructs than C-terminal conjugation (p<0.05). Seventeen CPP conjugates were identified as the most promising based on translational efficacy, thermodynamic stability, aggregation risk, folding rate, flexibility, and protease susceptibility.
Behzadipour, Yasaman; Hemmati, Shiva ·
RPEP-04077 · 2019The chimeric protein vaccine platform generated potent CD4 helper and CD8 cytotoxic T cell responses against model antigens, neoantigens, and self-antigens in mice. It demonstrated high antitumor efficacy across several murine tumor models. A human vaccine candidate designed for colorectal cancer treatment showed safety and immunogenicity in a non-human primate model (cynomolgus macaques). The three-domain design (CPP + multiantigenic domain + TLR agonist) enabled simultaneous antigen-presenting cell activation and antigen cross-presentation.
Belnoue, Elodie; Mayol, Jean-François; Carboni, Susanna; Di Berardino Besson, Wilma; Dupuychaffray, Eloise; Nelde, Annika; Stevanovic, Stefan; Santiago-Raber, Marie-Laure; Walker, Paul R; Derouazi, Madiha ·
RPEP-04081 · 2019Cyclic and linear peptides with an Arg-DHis-Arg template and two lipidic moieties achieved high intracellular siRNA delivery. The histidine residues enabled pH-dependent endosomal release: hydrogen bonding between Arg and His side chains was stable at physiological pH but dissociated at the lower pH inside endosomes, triggering cargo release.
Peptides with two linoleyl moieties demonstrated ERK1/2 gene silencing in TNBC cells comparable to the commercial reagent HiPerFect. The peptides were protease-resistant and provided serum stability to siRNA. Combination therapy using ERK1/2-silencing siRNA delivered via gramicidin plus doxorubicin was more effective than siRNA monotherapy for TNBC treatment.
Biswas, Abhijit; Chakraborty, Kasturee; Dutta, Chiranjit; Mukherjee, Sanchita; Gayen, Paramita; Jan, Somnath; Mallick, Argha Mario; Bhattacharyya, Dhananjay; Sinha Roy, Rituparna ·
RPEP-04094 · 2019Hepcidin, a cysteine-rich cationic peptide with four disulfide bridges belonging to the β-defensin family, has been evolutionarily conserved across vertebrates with dual functions in innate immunity and iron homeostasis. Analysis of hepcidin genes from 17 vertebrate species showed that while some species have multiple hepcidin homologs, generally only one copy per species serves as the iron regulator.
The pigeon (Columba livia) was a notable exception, with hepcidin sequences that deviate from the one-iron-regulator-per-species pattern. This evolutionary analysis highlights the functional diversification of hepcidin genes across the vertebrate lineage.
Boumaiza, Mohamed; Abidi, Sondes ·
RPEP-04095 · 2019This review consolidates evidence that insect cecropins and their synthetic analogs are effective against multi-drug resistant (MDR) bacteria while showing low toxicity to mammalian cells. Natural cecropins are primarily active against Gram-negative bacteria, while engineered analogs can target both Gram-positive and Gram-negative pathogens. The peptides also exhibit anti-inflammatory properties, and nanotechnology-based delivery methods may overcome their stability and bioavailability limitations.
Brady, Daniel; Grapputo, Alessandro; Romoli, Ottavia; Sandrelli, Federica ·
RPEP-04097 · 2019Succinylated gelatin (Gelofusine) reduced kidney accumulation of the radiolabeled GLP-1 receptor peptide 111In-exendin-4 by 18.1% in humans without affecting pancreatic uptake. In 3 of 10 volunteers, the reduction was sufficient to better distinguish the pancreatic tail from kidney signal on SPECT/CT imaging. Dosimetric calculations from 5 insulinoma patients estimated that tumor radiation doses of 30.3-127.8 Gy could be achieved, potentially increasing to 156.1 Gy with Gelofusine — making peptide receptor radionuclide therapy feasible for GLP-1R-positive insulinomas.
Buitinga, Mijke; Jansen, Tom; van der Kroon, Inge; Woliner-van der Weg, Wietske; Boss, Marti; Janssen, Marcel; Aarntzen, Erik; Béhé, Martin; Wild, Damian; Visser, Eric; Brom, Maarten; Gotthardt, Martin · Clinical (Crossover + Dosimetry)
RPEP-04098 · 2019Ghrelin, the hunger hormone released by the stomach during food restriction, promotes the growth of new neurons in the hippocampus — the brain's memory center. This review synthesizes accumulating evidence that ghrelin provides a biological link between nutritional status and brain function, specifically by stimulating adult hippocampal neurogenesis.
The review also highlights that disrupted neurogenesis is connected to cognitive decline in aging and neurodegenerative disease, positioning ghrelin as a potential protective factor for brain health when it's properly regulated.
Buntwal, Luke; Sassi, Martina; Morgan, Alwena H; Andrews, Zane B; Davies, Jeffrey S · Review
RPEP-04099 · 2019Bladder-drained (BD) transplant patients had significantly higher urine pH than enteric-drained (ED) patients (7.2 vs. 6.7; P=0.012). BD patients showed significantly decreased urinary lipocalin-2 compared to pre-transplant diabetics (P significant). In vitro, pancreatic enzymes (pancreatin at >12,500 amylase units) directly degraded β-defensin 2, eliminating its antimicrobial activity. The elevated pH from pancreatic secretions further impaired defense peptide function and promoted E. coli growth.
Byrne, Matthew; Singh, Aminder; Mowbray, Catherine A; Aldridge, Phillip D; Drage, Lauren K L; Ali, Ased S M; Bates, Lucy; Hall, Judith; Wilson, Colin ·
RPEP-04101 · 2019Five unique defensin sequences (holosins 1-5) were identified from the I. holocyclus transcriptome, all sharing conserved molecular features with other tick defensins including the γ-core motif.
Antimicrobial testing showed:
- Holosins 2 and 3 were very active against Gram-positive bacteria S. aureus and Listeria grayi
- Holosins 2 and 3 also killed the fungus Fusarium graminearum and yeast Candida albicans, with 5 µM sufficient to abrogate growth
- Synthetic γ-cores (HoloTickCores 1-4) generally showed lower activity than mature defensins
- Exception: HoloTickCore 2 had activity comparable to mature holosin 2 against the Gram-negative bacterium E. coli
This reveals a multigene defensin family in I. holocyclus with broad-spectrum antimicrobial activity.
Cabezas-Cruz, Alejandro; Tonk, Miray; Bleackley, Mark R; Valdés, James J; Barrero, Roberto A; Hernández-Jarguín, Angélica; Moutailler, Sara; Vilcinskas, Andreas; Richard-Forget, Florence; Anderson, Marilyn A; Rodriguez-Valle, Manuel ·
RPEP-04102 · 2019Spider venom-derived cysteine knot peptides modulate voltage-gated sodium channels (NaV) by binding to structural domains outside the channel pore, allosterically promoting either opening or closing. This mechanism produces diverse effects including modified pain responses, muscle paralysis, cardiac arrest, and numbness.
Critically, some of these peptides show subtype selectivity — they can distinguish between different NaV subtypes. This is therapeutically important because specific NaV subtypes (like NaV1.7 for pain, NaV1.1 for epilepsy) are implicated in different disorders. Subtype-selective spider venom peptides could theoretically target disease-relevant channels while sparing others, avoiding the broad side effects of current sodium channel drugs.
Cardoso, Fernanda C; Lewis, Richard J ·
RPEP-04109 · 2019Substance P, an 11-amino-acid neuropeptide long assumed to only cause pain, actually plays a paradoxical dual role — it can both promote pain (nociception) and suppress it (anti-nociception). The direction of its effect depends on which ion channels it modulates and which cell types express the NK1 receptor.
The review maps how SP activates different downstream signaling pathways through NK1 receptors in different cell types, engaging calcium channels, potassium channels, and other ion channels to produce opposite pain outcomes. This dual nature suggests that targeting the anti-nociceptive SP-NK1R pathway could lead to a new class of painkillers.
Chang, Chu-Ting; Jiang, Bo-Yang; Chen, Chih-Cheng · Review
RPEP-04110 · 2019Backbone-cyclized, cysteine-rich polypeptides — including cyclotides, θ-defensins, and sunflower trypsin inhibitor peptides — serve as exceptionally stable molecular scaffolds for designing new drugs and bioimaging tools. These cyclic peptides are far more resistant to chemical, thermal, and biological degradation than linear peptides. They tolerate extensive sequence modification while maintaining structure, can cross cell membranes, and can modulate intracellular protein-protein interactions both in vitro and in vivo.
Chaudhuri, Dipankar; Aboye, Teshome; Camarero, Julio A ·
RPEP-04111 · 2019Researchers developed MARIA, a deep learning system that predicts which peptides will be presented by HLA class II molecules to trigger immune responses. Unlike previous tools that relied only on binding data, MARIA integrates four types of information: binding measurements, mass spectrometry-identified peptide-HLA sequences, gene expression levels, and protease cleavage patterns.
MARIA achieved an AUC of 0.89–0.92, significantly outperforming existing prediction methods. When validated against independent cancer studies, peptides scored high by MARIA were more likely to trigger strong CD4+ T cell responses.
The tool can identify immunogenic epitopes for both cancer immunotherapy (neoantigens) and autoimmune disease research.
Chen, Binbin; Khodadoust, Michael S; Olsson, Niclas; Wagar, Lisa E; Fast, Ethan; Liu, Chih Long; Muftuoglu, Yagmur; Sworder, Brian J; Diehn, Maximilian; Levy, Ronald; Davis, Mark M; Elias, Joshua E; Altman, Russ B; Alizadeh, Ash A · Computational Study
RPEP-04113 · 2019Thymosin beta 4 protected endothelial progenitor cells (EPCs) from damage caused by advanced glycation endproducts (AGEs) — toxic compounds that accumulate in diabetes. The mechanism works through a specific molecular pathway: thymosin beta 4 suppresses microRNA-34a, which in turn allows the anti-apoptotic protein Bcl-2 to remain active. When microRNA-34a was artificially increased or Bcl-2 was knocked down, the protective effect of thymosin beta 4 was abolished, confirming this pathway is essential.
The protection manifested as improved cell survival, reduced programmed cell death (apoptosis), lower oxidative stress, and better mitochondrial function.
Chen, Qi; Shen, Zhida; Mao, Yanjun; Li, Qinfeng; Liu, Yu; Mei, Menghan; Qiu, Fuyu; Wang, Meihui · In Vitro
RPEP-04119 · 2019Botulinum toxin A and B directly inhibited mast cell degranulation in both human and mouse mast cells. The mechanism involves cleaving SNAP-25 (toxin A) and VAMP2 (toxin B), which are essential for the vesicle fusion machinery that mast cells use to release inflammatory mediators. Mouse mast cells express the botulinum toxin receptor Sv2, confirming they are direct targets. In a mouse rosacea model using LL-37 (the antimicrobial peptide linked to rosacea), botulinum toxin A pretreatment significantly reduced skin redness, mast cell degranulation, and expression of rosacea biomarkers.
Choi, Jae Eun; Werbel, Tyler; Wang, Zhenping; Wu, Chia Chi; Yaksh, Tony L; Di Nardo, Anna ·