RPEP-03760 · 2018Researchers analyzing black market growth-promoting products discovered several previously unknown compounds. They found a modified form of human growth hormone with 192 amino acids instead of the normal 191 — it had an extra alanine added to one end, giving it a slightly different molecular mass (22,195 Da versus the normal 22,124 Da).
They also identified three novel GHRP analogs: Gly-GHRP-6, Gly-GHRP-2, and Gly-Ipamorelin. Each is a known growth hormone-releasing peptide with an extra glycine residue attached to the N-terminus. The identities of Gly-Ipamorelin and Gly-GHRP-2 were confirmed by synthesizing the peptides from scratch and comparing them. Preliminary in-vitro metabolism experiments were also conducted on these new analogs.
Krug, Oliver; Thomas, Andreas; Malerød-Fjeld, Helle; Dehnes, Yvette; Laussmann, Tim; Feldmann, Ingo; Sickmann, Albert; Thevis, Mario · Analytical / Forensic Study
RPEP-03762 · 2018Dulaglutide demonstrated robust A1c reduction ranging from -0.78% to -1.64% over 52-104 weeks in head-to-head comparisons, consistently outperforming metformin, insulin glargine, and sitagliptin. As add-on therapy, it provided additional A1c lowering of -1.4% to -1.44% beyond monotherapy with glimepiride or glargine.
Dulaglutide also outperformed exenatide when added to metformin plus pioglitazone, and beat glargine when added to metformin plus glimepiride. It was non-inferior to liraglutide when added to metformin. In nearly all AWARD trials, full-dose dulaglutide enabled significantly more patients to reach their A1c goals. Pooled safety data showed no increased risk of pancreatitis or neoplasm.
Kugler, Anne J; Thiman, Michael L ·
RPEP-03765 · 2018After 12 months, the collagen peptide group showed significant increases in bone mineral density compared to placebo at both measurement sites. Spine T-score changed by +0.1 in the collagen group vs. -0.03 in placebo (p=0.030). Femoral neck T-score changed by +0.09 vs. -0.01 (p=0.003). Bone formation marker P1NP increased significantly in the collagen group (p=0.007), while bone degradation marker CTX-1 increased significantly in the placebo group (p=0.011), indicating a favorable shift in the balance between bone formation and resorption.
König, Daniel; Oesser, Steffen; Scharla, Stephan; Zdzieblik, Denise; Gollhofer, Albert ·
RPEP-03769 · 2018Intranasal Semax (1%) produced a measurable increase in the volume of the default mode network's rostral subcomponent (medial frontal cortex) compared to placebo, as detected by resting state fMRI. This effect was visible within 5 to 20 minutes of nasal administration. The finding confirms that Semax reaches the brain and alters neural network activity in a specific, topographically defined manner.
Lebedeva, I S; Panikratova, Ya R; Sokolov, O Yu; Kupriyanov, D A; Rumshiskaya, A D; Kost, N V; Myasoedov, N F ·
RPEP-03775 · 2018In two mouse models of acute pancreatitis (caerulein/LPS and L-arginine), LTB4 and its receptor BLT1 were markedly upregulated. Blocking BLT1 with the antagonist LY293111 achieved three effects: attenuated pancreatitis severity, decreased neutrophil reverse transendothelial migration (rTEM) into the circulation, and alleviated acute lung injury severity.
In vitro, substance P treatment of pancreatic acinar cells increased LTB4 production through activation of protein kinase Cα (PKCα) and MAP kinases (ERK, p38, JNK). Blocking substance P's neurokinin-1 receptor with CP96345 significantly reduced pancreatitis severity and LTB4 levels. The complete pathway: substance P → NK-1 receptor → PKCα/MAPK → LTB4 production → BLT1 activation → neutrophil reverse migration → lung injury.
Li, Bin; Han, Xiao; Ye, Xin; Ni, Jianbo; Wu, Jianghong; Dai, Juanjuan; Wu, Zengkai; Chen, Congying; Wan, Rong; Wang, Xingpeng; Hu, Guoyong ·
RPEP-03778 · 2018In the rabbit model, erythema, papules, and telangiectasia were significantly diminished after 4 weeks of timolol treatment. The antimicrobial peptide LL-37 and the enzyme KLK5 were elevated in steroid-damaged skin but decreased after timolol treatment.
In human patients with facial telangiectasia, cheeks treated with timolol plus tacrolimus showed markedly reduced telangiectasia compared to tacrolimus alone by week 4. Both groups showed reduced erythema by week 1, but the timolol combination was significantly superior for visible blood vessels. Color measurements confirmed significant differences in L (lightness) and a (redness) values between treatment and control cheeks (p<0.05).
Li, Yan-Fei; Chen, Xiao-Yan; Lei, Tie-Chi ·
RPEP-03791 · 2018Lysine-to-arginine substitution in hydrocarbon-stapled antimicrobial heptapeptides produced variable effects on antimicrobial potency and selectivity. The outcomes depended on the number of substitutions and the positions substituted within the helical scaffold.
The results challenge the common assumption that arginine universally enhances AMP activity. In this stapled peptide scaffold, antimicrobial potency and selectivity were influenced by a complex interplay of structural and chemical changes accompanying the substitution, rather than simply the type of cationic residue. The study demonstrates that design rules from natural AMPs don't always transfer to engineered scaffolds.
Luong, Huy X; Kim, Do-Hee; Lee, Bong-Jin; Kim, Young-Woo ·
RPEP-03793 · 2018The neuropeptide fragment TLQP-62, derived from the VGF protein, produced rapid antidepressant-like effects when administered directly into the prefrontal cortex of mice. It also reversed depression-like behaviors caused by chronic social defeat stress — a validated mouse model of depression.
The mechanism was traced to a specific signaling cascade: TLQP-62 activates the TrkB receptor (the BDNF receptor), which triggers mTOR signaling, decreases the gene BICC1, and increases synaptic proteins including the AMPA receptor GluA1 subunit. When researchers blocked TrkB with the antagonist ANA-12, all of TLQP-62's antidepressant effects were abolished — confirming TrkB as the essential starting point of the cascade.
Lv, Dan; Chen, Yaping; Shen, Mengxin; Liu, Xu; Zhang, Yanhua; Xu, Jiangping; Wang, Chuang · Animal Study
RPEP-03794 · 2018From a library of 584 natural products screened using a luciferase reporter system driven by the avian β-defensin 9 (AvBD9) promoter, 21 compounds with a minimum Z-score of 2.0 were identified as defensin inducers.
Secondary screening in chicken macrophages and jejunal (gut) tissue explants confirmed most compounds induced defensin expression dose-dependently. The lead compound wortmannin, when given orally to chickens, enhanced AvBD9 gene expression in the duodenum and also induced most other chicken host defense peptide genes. Wortmannin synergized with butyrate to further amplify defensin production, and this combination significantly augmented the antibacterial activity of chicken monocytes.
Lyu, Wentao; Deng, Zhuo; Sunkara, Lakshmi T; Becker, Sage; Robinson, Kelsy; Matts, Robert; Zhang, Guolong ·
RPEP-03796 · 2018Adding the substance P antagonist aprepitant (80 mg/day for 7 days) to standard topical treatment provided no additional benefit over topical treatment alone in adults with moderate-to-severe atopic dermatitis. Both the aprepitant group (n=19) and the control group (n=20) showed improvements in disease severity (SCORAD), itch (pruritus), and scratching movements, but aprepitant did not enhance these improvements. This negative result suggests that blocking substance P via the NK-1 receptor does not meaningfully reduce eczema symptoms beyond what standard topical therapy achieves.
Lönndahl, Louise; Holst, Mikael; Bradley, Maria; Killasli, Hassan; Heilborn, Johan; Hall, Martin A; Theodorsson, Elvar; Holmberg, Jadwiga; Nordlind, Klas · Randomized Controlled Trial
RPEP-03802 · 2018ToAP2, a peptide from the scorpion Tityus obscurus, inhibited growth of four M. massiliense strains at a minimum bactericidal concentration of 200 µM. At this concentration, it inhibited 50% of bacterial growth in infected macrophages. In mice, ToAP2 reduced bacterial loads in liver, lung, and spleen by approximately 90%, matching clarithromycin effectiveness. Uniquely, ToAP2 also demonstrated chemotactic activity — recruiting monocytes (F4/80low Gr1), neutrophils (F4/80- Gr1), and eosinophils (F4/80+ Gr1+) — and modulated macrophage populations in infected mice, suggesting its in vivo efficacy is enhanced by immune cell recruitment beyond its direct antimicrobial action.
Marques-Neto, Lázaro M; Trentini, Monalisa M; das Neves, Rogério C; Resende, Danilo P; Procopio, Victor O; da Costa, Adeliane C; Kipnis, André; Mortari, Márcia R; Schwartz, Elisabeth F; Junqueira-Kipnis, Ana Paula ·
RPEP-03803 · 2018Cationic amphipathic antimicrobial peptides align parallel to the bacterial membrane surface, with their polar and non-polar sides mirroring the membrane interface. At low concentrations this causes transient membrane openings; at higher concentrations it leads to complete membrane disintegration. The SMART model captures this range of behaviors.
New biophysical data (isothermal titration calorimetry, circular dichroism, and dynamic light scattering) revealed that magainin 2 and PGLa together mediate liposome agglutination — causing membrane vesicles to clump together — suggesting a previously unrecognized mechanism behind their well-known synergistic antimicrobial action.
Marquette, Arnaud; Bechinger, Burkhard ·
RPEP-03807 · 2018Beta-defensins are multifunctional cationic peptides that manage host-microbe cross-talk across all mucosal systems (oral, respiratory, reproductive, enteric). They act as 'farmers' rather than simply 'killers' — curating microbial diversity to maintain homeostasis rather than eliminating microbes indiscriminately.
Some species show expansions in beta-defensin gene numbers, the functional significance of which is only recently appreciated. Beta-defensin expression is documented before birth, and disruptions in their regulation may contribute to maladaptive neonatal immune programming and subsequent disease susceptibility. The review also presents evidence that beta-defensins serve as sensors of homeostasis and immune vanguards at immunologically privileged sites.
Meade, Kieran G; O'Farrelly, Cliona ·
RPEP-03809 · 2018Gut microbiota stimulate innate lymphoid cells (ILCs) that travel to the pancreas and trigger pancreatic endocrine cells to produce a defensin peptide called mouse β-defensin 14 (mBD14). This defensin then activates a protective immune cascade: it signals through Toll-like receptor 2 to stimulate IL-4-secreting B cells, which activate regulatory macrophages, which in turn generate regulatory T cells that prevent autoimmune attack on insulin-producing cells.
The gut microbiota drives this process by producing aryl hydrocarbon receptor (AHR) ligands and butyrate, which promote IL-22 secretion by pancreatic ILCs. In non-obese diabetic (NOD) mice — a model for type 1 diabetes — both a dysbiotic microbiome and a low-affinity AHR gene variant explain why this protective defensin pathway fails, leading to diabetes development.
Miani, Michela; Le Naour, Julie; Waeckel-Enée, Emmanuelle; Verma, Subash Chand; Straube, Marjolène; Emond, Patrick; Ryffel, Bernhard; van Endert, Peter; Sokol, Harry; Diana, Julien · Animal Study
RPEP-03810 · 2018The review identifies a key paradox in amylin research for Alzheimer's disease. Multiple studies demonstrate that amylin and the amylin analog pramlintide (already FDA-approved for diabetes) can reduce amyloid burden in the brain and improve cognitive symptoms in Alzheimer's models.
However, contradictory evidence shows that amylin has a propensity to misfold and aggregate under certain conditions — similar to the amyloid-beta protein central to Alzheimer's pathology. This raises the possibility that amylin could contribute to, rather than treat, Alzheimer's disease. The author identifies several critical gaps including limited understanding of amylin system changes during aging, complexities of amylin receptor signaling, and how changing pathophysiology during AD progression might explain these conflicting results.
Mietlicki-Baase, Elizabeth G ·
RPEP-03818 · 2018A short-course peptide immunotherapy using ryegrass pollen peptides (LPP) significantly reduced allergic eye reactions in grass pollen-allergic adults. The 170 μg dose was the sweet spot: 51.2% of patients improved by at least one concentration step on the conjunctival provocation test (vs. 25.6% on placebo, p=0.023), and 39% became completely non-reactive to the allergen challenge compared to only 18% on placebo.
The treatment also triggered dose-dependent increases in protective IgG4 antibodies — 1.6-fold at 70 μg, 3.1-fold at 170 μg, and 3.9-fold at 370 μg — confirming that the immune system was being reprogrammed to tolerate the allergen. All of this was achieved with just 3-4 weeks of weekly injections, far shorter than conventional allergy immunotherapy.
Mösges, R; Kasche, E M; Raskopf, E; Singh, J; Sohlich, L; Astvatsatourov, A; Shah-Hosseini, K; Pirotton, S; Haazen, L; Durham, S R; Legon, T; Zadoyan, G; Shamji, M H · Rct
RPEP-03821 · 2018Combining thymosin α1 (Tα1), an immune-boosting peptide, with nucleos(t)ide analog antivirals (NUCs) may be more effective at clearing chronic hepatitis B than either approach alone. While NUCs suppress viral replication and Tα1 can help eliminate viral surface markers (HBsAg and HBeAg) in select patients, the combination leverages both viral suppression and immune activation. Small studies using Tα1 with NUCs showed encouraging results, and clinical trials combining entecavir with Tα1 were underway at the time of publication.
Naylor, P H; Mutchnick, M G · Review
RPEP-03827 · 2018By analyzing survival data from 265 urological cancer patients treated with personalized peptide vaccination (PPV), researchers identified specific peptides associated with significantly longer survival. In castration-resistant prostate cancer (CRPC), five peptides (SART3-109, PTHrP-102, HNPRL-140, SART3-302, and Lck-90) were linked to improved survival. In advanced urothelial cancer (UC), five different peptides (EGF-R-800, Lck-486, PSMA-624, CypB-129, and SART3-734) showed survival benefit.
All tumor-associated antigens coding for these candidate peptides were confirmed to be expressed in actual tumor tissues by immunohistochemistry, validating that the vaccines target proteins present on the cancers.
Noguchi, Masanori; Koga, Noriko; Moriya, Fukuko; Suekane, Shigetaka; Yutani, Shigeru; Yamada, Akira; Shichijo, Shigeki; Kakuma, Tatuyuki; Itoh, Kyogo · Retrospective Cohort
RPEP-03828 · 2018The antimicrobial peptide cathelicidin-2 (Cath-2) released from Atlantic salmon skin serves a completely unexpected second function: it's the chemical signal that sea lice (Lepeophtheirus salmonis) use to find their hosts. When exposed to Cath-2 at concentrations of 7, 70, and 700 ppb, sea lice copepodids showed triggered chemosensory neural activity, altered swimming behavior, and upregulated chemosensory-related genes.
This reveals a remarkable evolutionary twist — a peptide that evolved to defend against microbial infection is being exploited by a parasite as a homing beacon to locate its host.
Núñez-Acuña, Gustavo; Gallardo-Escárate, Cristian; Fields, David M; Shema, Steven; Skiftesvik, Anne Berit; Ormazábal, Ignacio; Browman, Howard I · Animal Study
RPEP-03831 · 2018Biomarker findings confirmed substance P/NK1R involvement:
- Substance P serum levels were increased in chronic prurigo patients compared to controls
- NK1R expression was higher in lesional versus non-lesional skin
Clinical trial results (randomized, placebo-controlled, split-sided, double-blind):
- Topical aprepitant reduced itch intensity by >50% from baseline by day 28 (VAS change: -35.2)
- Placebo vehicle also reduced itch by >50% (VAS change: -38.1)
- No significant difference between groups (p=0.76)
- Overall clinical scores improved in both groups with no significant between-group difference (p=0.32)
The strong placebo response in the split-sided design likely obscured any treatment effect.
Ohanyan, Tatevik; Schoepke, Nicole; Eirefelt, Stefan; Hoey, Gert; Koopmann, Witte; Hawro, Tomasz; Maurer, Marcus; Metz, Martin ·
RPEP-03834 · 2018GLP-2 stimulates intestinal growth through secondary mediators and Akt phosphorylation signaling, making it therapeutic for conditions like short bowel syndrome. However, rodent studies have shown that exogenous GLP-2 increases the growth and incidence of colon adenomas, raising concern that GLP-2 treatment could promote intestinal tumor development or progression.
Clinical studies show that exogenous GLP-2 treatment (as teduglutide) is well tolerated for up to 30 months, but the safety of longer treatment periods regarding intestinal cancer risk has not been established. The association between GLP-2 treatment and intestinal neoplasia in humans remains unclear.
Orhan, Adile; Gögenur, Ismail; Kissow, Hannelouise · Review
RPEP-03835 · 2018Phase 2 and Phase 3 trial data for all four CGRP pathway antibodies confirmed consistent efficacy for both episodic and chronic migraine prevention. The efficacy was described as modest over placebo and broadly comparable to available oral preventive treatments.
The key differentiator was tolerability: safety reviews found no significant difference in total adverse events between the antibodies and placebo injections, except possibly for dizziness. Common side effects (upper respiratory tract infection, nasopharyngitis, nausea, injection-site pain, back pain) occurred at similar rates in treatment and placebo groups. The mechanism of action appears to be primarily peripheral, though central nervous system contributions could not be ruled out.
Paemeleire, Koen; MaassenVanDenBrink, Antoinette ·
RPEP-03836 · 2018This review traces the evolution of natriuretic peptides from basic biology to clinical application. ANP and BNP are released by the heart during overload and act as natural counterweights to the renin-angiotensin-aldosterone system — lowering blood pressure, reducing fluid retention, and inhibiting harmful cardiac remodeling.
BNP and its precursor fragment NT-proBNP have become established diagnostic and prognostic biomarkers for heart failure. However, the body's natriuretic peptide response during heart failure is insufficient to prevent disease progression. Of various therapeutic strategies attempted — including synthetic peptide analogs and inhibition of the enzyme that degrades natriuretic peptides (NEP) — only the combined NEP inhibitor/angiotensin receptor blocker sacubitril/valsartan demonstrated clinical success in reducing cardiovascular mortality and morbidity.
Pagel-Langenickel, Ines ·
RPEP-03839 · 2018Molecular dynamics simulations of 12 oligopeptides bound to HLA molecules revealed a previously unknown mechanism: some peptides cause the HLA binding groove to contract upon binding, making the peptide-HLA complex incompatible with T cell receptor recognition. This means that just because a peptide can bind to an HLA molecule does not mean it will trigger an immune response.
Based on this insight, the authors developed SEFF12MC, an atom-based computational method that predicts immunogenicity by assessing whether a peptide-HLA complex can further bind to a T cell receptor. SEFF12MC achieved a 100% success rate in predicting immunogenicity of the 12 test peptides, compared to only 25-50% success rates for 11 existing residue-based methods including NetMHC-4.0.
Pang, Yuan-Ping; Elsbernd, Laura R; Block, Matthew S; Markovic, Svetomir N ·
RPEP-03840 · 2018Across the reviewed clinical studies, thymosin alpha-1 treatment — both alone and in combination with anti-inflammatory therapies — reduced mortality rates in sepsis patients, improved HLA-DR expression on monocytes (a key marker of immune competence), and diminished the incidence of secondary infections. The authors identify Tα1 as a promising adjuvant therapy but note that the heterogeneity of sepsis makes it difficult to generalize results. They recommend that future trials specifically enroll immunosuppressed sepsis patients to better demonstrate efficacy.
Pei, Fei; Guan, Xiangdong; Wu, Jianfeng ·
RPEP-03843 · 2018Researchers discovered a new class of noncharged cell-penetrating oligoTEAs (CPOTs) that entered cells extensively and rapidly across multiple cell lines with low toxicity. These synthetic oligomers outperformed R9 — a widely used nine-arginine cell-penetrating peptide — in cellular uptake efficiency.
Unlike traditional cationic cell-penetrating peptides that rely on positive charges (which cause unwanted biological interactions and rapid degradation), CPOTs achieve cell entry through a charge-independent mechanism. This makes them more stable in serum and better candidates for delivering water-soluble drugs inside cells.
Phan, Ngoc N; Li, Connie; Alabi, Christopher A ·
RPEP-03851 · 2018Self-assembling peptide nanotubes made from diphenylalanine (FF) completely eradicated mature Staphylococcus aureus biofilms — the first time peptide nanotubes have been shown to destroy bacterial biofilms. The NH2-FF-COOH variant was most effective, achieving greater than 99.9% biofilm reduction at 5 mg/mL and complete biofilm kill at 10 mg/mL after 24 hours, with minimal toxicity to mammalian cells.
Scanning electron microscopy revealed the nanotubes work by degrading the biofilm's protective polysaccharide matrix and disrupting bacterial cell membranes through ion channel formation and surfactant-like action. Switching to D-amino acid isomers (NH2-ff-COOH) maintained antibiofilm activity, while amidated forms (NH2-FF-NH2) were more toxic and less effective.
Porter, Simon L; Coulter, Sophie M; Pentlavalli, Sreekanth; Thompson, Thomas P; Laverty, Garry · In Vitro
RPEP-03854 · 2018Genipin cross-linking significantly increased the stiffness and resiliency of FAQ(LDLK)3 self-assembling peptide hydrogels in a dose- and time-dependent manner. The cross-linking also extended bioabsorption time and altered molecular arrangements.
Using the optimized protocol, researchers achieved a breakthrough: electrospinning cross-linked SAPs into nanofibers to create self-standing, water-stable, and flexible fibrous mats and micro-channels entirely made of peptides — the first time this was accomplished. This was possible because the genipin cross-links provided sufficient mechanical integrity for the peptide scaffolds to maintain their structure independently.
Pugliese, Raffaele; Maleki, Mahboubeh; Zuckermann, Ronald N; Gelain, Fabrizio ·
RPEP-03858 · 2018All four anti-CGRP monoclonal antibodies (eptinezumab, fremanezumab, galcanezumab, and erenumab) proved effective, tolerable, and safe for migraine prevention in phase II clinical trials. Mean monthly migraine day reductions ranged from 3.4 to 6.3 days after 8-12 weeks of treatment, with placebo-subtracted benefit of 1 to 2.18 days. Up to 32% of patients achieved total migraine freedom. No substance class-specific adverse events or treatment-related serious adverse events occurred. The antibodies likely act peripherally since their large size prevents blood-brain barrier penetration, revealing that peripheral CGRP signaling plays a pivotal role in migraine.
Raffaelli, Bianca; Reuter, Uwe ·
RPEP-03860 · 2018Vitamin D supplementation (calcitriol) in asthma patients led to significantly increased serum levels of the anti-inflammatory cytokine IL-10 and the antiviral cytokine IFNγ, while pro-inflammatory cytokines IL-5, IL-9, and IL-13 decreased significantly. IgE and eosinophil levels also dropped, though allergen sensitivity remained unchanged.
Respiratory infections were drastically reduced in the vitamin D group, and this reduction was directly related to the number of patients who had high IL-10 and IFNγ levels and expressed the antimicrobial peptide cathelicidin LL-37 in their sputum. This links vitamin D's infection-fighting benefit to its ability to stimulate natural antimicrobial peptide production.
Ramos-Martínez, E; López-Vancell, M R; Fernández de Córdova-Aguirre, J C; Rojas-Serrano, J; Chavarría, A; Velasco-Medina, A; Velázquez-Sámano, G ·
RPEP-03866 · 2018Across two large prospective cohorts (N=892 and N=2,427), three distinct plasma NPY (pNPY) trajectories were identified from measurements taken before and shortly after military deployment. However, in both cohorts:
- pNPY trajectories were not related to the level of PTSD symptoms over time
- Pre-deployment pNPY levels alone did not predict PTSD development
This challenges previous smaller studies that suggested high NPY levels might serve as a resilience biomarker. The current findings suggest limited usefulness of peripherally measured NPY (blood levels) for predicting PTSD risk, though central nervous system NPY levels might still be relevant.
Reijnen, Alieke; Geuze, Elbert; Eekhout, Iris; Maihofer, Adam X; Nievergelt, Caroline M; Baker, Dewleen G; Vermetten, Eric ·
RPEP-03873 · 2018HM01, an orally bioavailable ghrelin receptor (GHS-R1A) agonist that penetrates the brain, reduced emesis induced by cisplatin (30 mg/kg) and motion (1 Hz horizontal displacement) in Suncus murinus at doses of 1–30 mg/kg given orally.
Importantly, HM01 at just 3 mg/kg enhanced the anti-emetic effects of palonosetron alone and the palonosetron plus netupitant combination. However, HM01 was ineffective against emesis caused by nicotine or copper sulfate, indicating its anti-emetic action is selective to certain pathways. HM01 also improved food and water intake in animals treated with cisplatin or nicotine.
Rudd, John A; Chan, Sze W; Ngan, Man P; Tu, Longlong; Lu, Zengbing; Giuliano, Claudio; Lovati, Emanuela; Pietra, Claudio ·
RPEP-03881 · 2018Alpha-defensin (HNP 1-3) levels were significantly elevated in both plasma and bronchoalveolar lavage fluid (BALF) of myositis-associated ILD patients compared to healthy controls. Plasma HNP levels correlated with total cell counts in BALF. BALF HNP levels positively correlated with serum surfactant protein-A and the percentage of neutrophils in lung fluid.
In patients positive for anti-aminoacyl-tRNA synthetase (anti-ARS) antibodies, BALF HNP levels also correlated with the percentage of reticular opacities on high-resolution CT scans. However, survival did not differ between patients with higher and lower HNP levels.
Sakamoto, Noriho; Ishimoto, Hiroshi; Kakugawa, Tomoyuki; Satoh, Minoru; Hasegawa, Tomoko; Tanaka, Shin; Hara, Atsuko; Nakashima, Shota; Yura, Hirokazu; Miyamura, Takuto; Koyama, Hanako; Morita, Towako; Nakamichi, Seiko; Obase, Yasushi; Ishimatsu, Yuji; Mukae, Hiroshi ·
RPEP-03889 · 2018Using a sustained-release oxyntomodulin analogue (OX-SR) in rats, researchers definitively showed that the energy expenditure (calorie-burning) effect of oxyntomodulin occurs through the glucagon receptor, not the GLP-1 receptor. When the GLP-1 receptor was blocked with Exendin 9-39, OX-SR still increased oxygen consumption (energy burning). But when glucagon receptor activity was eliminated, the energy expenditure boost completely disappeared.
This resolves a key controversy about how oxyntomodulin works: its appetite-suppressing effects come mainly through GLP-1 receptor activation, while its calorie-burning effects require glucagon receptor activation. Both receptor activities are needed for optimal weight loss.
Scott, R; Minnion, J; Tan, T; Bloom, S R · Animal
RPEP-03891 · 2018The review identifies multiple mechanisms by which GLP-1-based therapies could treat NAFLD:
- GLP-1 receptor agonists reduce liver inflammation and fibrosis through direct and indirect mechanisms
- GLP-1 RAs reduce body weight, improving NAFLD independently of direct liver effects
- Glucagon receptor agonism increases lipid oxidation and thermogenesis
- Glucagon receptor signaling is disrupted in NAFLD, suggesting a therapeutic target
- Supra-physiological glucagon receptor agonism could represent a novel NAFLD treatment approach
- Dual GLP-1/glucagon co-agonists combine appetite reduction with increased fat burning
- No pharmacotherapy was approved for NAFLD at the time of writing
Seghieri, Marta; Christensen, Alexander S; Andersen, Andreas; Solini, Anna; Knop, Filip K; Vilsbøll, Tina ·
RPEP-03892 · 2018Different commercial immunoassays for BNP and NT-proBNP produce markedly different results that are not comparable to each other. There is currently no certified reference material or standardized calibration approach for either biomarker, meaning that diagnostic cut-off values are method-dependent rather than universal.
The lack of equivalence stems partly from the complex nature of circulating BNP-related peptides — BNP exists in multiple forms in blood (precursors, fragments, glycosylated variants), and different assays detect different combinations of these forms.
Semenov, Alexander G; Feygina, Evgeniya E · Review
RPEP-03901 · 2018A novel cyclic form of the collagen peptide Pro-Hyp was detected in human blood for the first time after ingestion of collagen hydrolysate. Cyclic Pro-Hyp peaked in plasma at 2 hours post-ingestion, reaching levels of 0.14–0.34 nmol/mL — approximately 5% of the linear Pro-Hyp concentration.
In cell culture experiments, cyclic Pro-Hyp at 7 nmol/mL significantly enhanced the growth rate of mouse skin fibroblasts on collagen gel more than the linear form, suggesting it may be more biologically active despite its lower concentration.
Shigemura, Yasutaka; Iwasaki, Yu; Tateno, Mana; Suzuki, Asahi; Kurokawa, Mihoko; Sato, Yoshio; Sato, Kenji · Pilot Study
RPEP-03902 · 2018Glypican-3 peptide vaccines successfully induced cancer-specific cytotoxic T lymphocytes (CTLs) in most patients across multiple clinical trials (five registered trials). The peptide showed extreme cancer specificity when restricted to HLA-A24 and HLA-A2 molecules. The review also found that neoantigen-based personalized immunotherapy shows potential for eliciting cancer regression, and both approaches may complement immune checkpoint inhibitors for patients who don't respond to checkpoint therapy alone.
Shimizu, Yasuhiro; Suzuki, Toshihiro; Yoshikawa, Toshiaki; Tsuchiya, Nobuhiro; Sawada, Yu; Endo, Itaru; Nakatsura, Tetsuya ·
RPEP-03908 · 2018LFchimera, a heterodimeric peptide construct combining the lactoferrampin and lactoferricin domains of bovine lactoferrin, inhibited host-cell invasion by both Yersinia enterocolitica and Yersinia pseudotuberculosis (Y. pestis simulants) in vitro.
The anti-invasion effect was host-cell mediated rather than bacteria-mediated — meaning the peptide altered the human cells' susceptibility to invasion rather than directly killing or disabling the bacteria. Additionally, co-exposure of HeLa epithelial cells to LFchimera and the bacterial strains triggered pro-inflammatory cytokine release, suggesting the peptide also stimulates the host immune response.
Sijbrandij, Tjitske; Ligtenberg, Antoon J; Nazmi, Kamran; van den Keijbus, Petra A M; Veerman, Enno C I; Bolscher, Jan G M; Bikker, Floris J ·
RPEP-03909 · 2018BPC 157, a pentadecapeptide (15 amino acids) native to human gastric juice, demonstrated a three-part cytoprotective mechanism: (1) stomach cell protection, (2) endothelium (blood vessel lining) protection, and (3) active blood vessel function control. After perforating injuries, BPC 157 activated blood vessels to grow toward the defect. After vessel obstruction, it activated collateral vessels to bypass the blockage.
The peptide prevented and reversed thrombosis in both arterial and venous models, attenuated bleeding and low platelet counts after amputation, and counteracted the effects of both L-NAME and L-arginine on the nitric oxide system. It has already entered clinical trials for ulcerative colitis and multiple sclerosis.
Sikiric, Predrag; Rucman, Rudolf; Turkovic, Branko; Sever, Marko; Klicek, Robert; Radic, Bozo; Drmic, Domagoj; Stupnisek, Mirjana; Misic, Marija; Vuletic, Lovorka Batelja; Pavlov, Katarina Horvat; Barisic, Ivan; Kokot, Antonio; Peklic, Marina; Strbe, Sanja; Blagaic, Alenka Boban; Tvrdeic, Ante; Rokotov, Dinko Stancic; Vrcic, Hrvoje; Staresinic, Mario; Seiwerth, Sven ·
RPEP-03911 · 2018Inulin dose-dependently decreased caloric intake and respiratory quotient; improved glucose tolerance; increased Bacteroidetes and Bifidobacterium while decreasing Clostridium clusters I and IV; increased butyryl-CoA:acetate CoA-transferase (butyrate production); upregulated PYY, CCK, and proglucagon gene transcripts in cecum and colon; and increased plasma PYY and GLP-1 concentrations. Critically, 25% inulin attenuated the reduction in energy expenditure seen with equivalent calorie restriction (pair-fed controls) and decreased adiposity — showing metabolic benefits independent of calorie restriction alone.
Singh, Arashdeep; Zapata, Rizaldy C; Pezeshki, Adel; Reidelberger, Roger D; Chelikani, Prasanth K ·
RPEP-03917 · 2018This historical review traces more than a century of research on how sensory nerves drive inflammation — a process called neurogenic inflammation. Sensory nerves don't just detect pain; they actively release peptides that dilate blood vessels and recruit immune cells.
The key neuropeptides identified as drivers of neurogenic inflammation include substance P (which causes vasodilation and plasma leakage) and CGRP (calcitonin gene-related peptide, a potent vasodilator). Sensory nerves also release anti-inflammatory peptides like endogenous opioids and somatostatin, showing the system has built-in brakes. The discovery of TRP channels (particularly TRPV1) revealed how these nerves sense environmental stimuli like heat, chemicals, and injury — providing the molecular mechanism linking tissue damage to neuropeptide release and inflammation.
Sousa-Valente, João; Brain, Susan D · Review
RPEP-03920 · 2018The review identifies several categories of peptide-based anti-obesity drugs in development:
- **GLP-1 analogs**: Semaglutide (injectable and oral forms) leading the field
- **Amylin mimetics**: Davalintide and dual amylin/calcitonin receptor agonists (DACRAs)
- **Dual agonists**: GLP-1/glucagon receptor agonists (oxyntomodulin analogs)
- **Triple agonists**: Tri-agonist 1706 targeting GLP-1, GIP, and glucagon receptors simultaneously
- **Other peptide targets**: Peptide YY, setmelanotide (melanocortin receptor), neuropeptide Y antagonists (velneperit), leptin analogs (pramlintide-metreleptin combination)
- **Anti-obesity vaccines**: Targeting ghrelin and somatostatin
The pipeline reflects growing understanding that obesity involves multiple neurohormonal pathways, and that targeting several simultaneously may produce superior weight loss.
Srivastava, Gitanjali; Apovian, Caroline ·
RPEP-03921 · 2018Thymosin alpha 1 (Tα1) demonstrated a dual mechanism against cystic fibrosis (CF) in preclinical models: it both corrected the underlying CFTR protein defect and reduced the chronic hyperinflammation that drives progressive lung damage. Tα1 achieves this through activation of the indoleamine 2,3-dioxygenase (IDO) pathway, which promotes immune tolerance and breaks the cycle of chronic inflammation. This represents a single peptide that addresses two of CF's core problems simultaneously.
Stincardini, Claudia; Renga, Giorgia; Villella, Valeria; Pariano, Marilena; Oikonomou, Vasilis; Borghi, Monica; Bellet, Marina M; Sforna, Luigi; Costantini, Claudio; Goldstein, Allan L; Garaci, Enrico; Romani, Luigina ·
RPEP-03926 · 2018Four symmetrical peptide variants of lactoferricin B(18-28) (KCRRWQWRMKK) were engineered:
- **KW-WK** (KWRRWQWRRWK): enhanced antibacterial activity, safe
- **FP-PF** (FPRRWQWRRPF): enhanced antibacterial activity, safe
- **KK-KK** (KKRRWQWRRKK): enhanced antibacterial activity, safe
- **FW-WF** (FWRRWQWRRWF): enhanced antibacterial activity, but hemolytic (toxic to red blood cells)
All four peptides showed significantly greater antibacterial activity than the original LFcinB(18-28), demonstrating that symmetrical amino acid sequences enhance antimicrobial potency. The peptides killed bacteria by disrupting membrane integrity through cationic and amphipathic interactions with anionic bacterial membranes.
Sun, Changbao; Li, Yingying; Cao, Songsong; Wang, Haimei; Jiang, Chenggang; Pang, Shiyue; Hussain, Muhammad Altaf; Hou, Juncai ·
RPEP-03935 · 2018Cath-A inhibited growth of A. baumannii clinical isolates from medical instruments at MIC values of 8-16 μg/mL. Against P. aeruginosa, MICs ranged from 16 to ≥256 μg/mL. The peptide significantly removed established biofilms of both species. Cath-A showed minimal hemolytic and cytotoxic activity against eukaryotic cells. Recombinant production in E. coli BL21 using pET-32a(+) vector with thioredoxin fusion yielded 17.6 mg/L of partially purified peptide with confirmed antimicrobial activity after enterokinase cleavage.
Tajbakhsh, Mercedeh; Akhavan, Maziar Mohammad; Fallah, Fatemeh; Karimi, Abdollah ·
RPEP-03943 · 2018This comprehensive review traces the development of anti-CGRP therapies from the first proof-of-concept with olcegepant in 2004 to the FDA approval of erenumab in May 2018 — the first monoclonal antibody approved for migraine prevention. It summarizes randomized controlled trial data for four anti-CGRP monoclonal antibodies (erenumab, galcanezumab, fremanezumab, eptinezumab) and two small-molecule gepants (ubrogepant, rimegepant) for acute migraine treatment.
Galcanezumab also showed effectiveness in preventing episodic cluster headache, expanding the potential uses of this drug class beyond migraine.
Tepper, Stewart J · Review
RPEP-03949 · 2018Traditional diabetes drugs (insulin, metformin, sulfonylureas, meglitinides) all require dose adjustments or carry heightened risks in kidney impairment. Among newer agents, GLP-1 receptor agonists liraglutide and semaglutide demonstrated reductions in adverse renal and cardiovascular events. DPP-4 inhibitors require dose adjustments except linagliptin. All SGLT2 inhibitors were contraindicated at very low kidney function (eGFR <30). Some DPP-4 inhibitors reduce albuminuria. The review emphasizes individualized therapy selection based on kidney function stage.
Tong, Lili; Adler, Sharon ·
RPEP-03952 · 2018Cirrhotic patients (n=67) showed diminished HD5 and HD6 expression compared to healthy controls (n=27; p=0.000287 and p=0.000314 respectively). Decompensated cirrhosis patients (n=40) had even lower defensin expression than compensated patients (n=27; p=0.025 and p=0.041). Cirrhotic patients had significantly higher serum endotoxin levels (p<0.0001).
HD5 and HD6 expression showed strong inverse correlations with endotoxin levels (r=-0.790 and r=-0.777, both p<0.0001). Intraepithelial T-lymphocytes were decreased in decompensated cirrhosis versus controls (p=0.002), but B-lymphocyte infiltrates did not differ between groups.
Tsiaoussis, Georgios I; Papaioannou, Eleni C; Kourea, Eleni P; Assimakopoulos, Stelios F; Theocharis, Georgios I; Petropoulos, Michalis; Theopistos, Vasileios I; Diamantopoulou, Georgia G; Lygerou, Zoi; Spiliopoulou, Iris; Thomopoulos, Konstantinos C ·
RPEP-03954 · 2018Proteomic analysis of 246 patients (REVE-2 study) identified increased plasma clusterin in patients with high left ventricular remodeling after first anterior MI. In rat MI models, cardiac clusterin expression increased and correlated with remodeling parameters.
Silencing clusterin in hypertrophied cardiomyocytes decreased cell size, ANP and BNP expression, and ERK1/2 activity — establishing a prohypertrophic role. Both precursor (p-CLU) and mature (m-CLU) forms were increased in failing human hearts. Circulating clusterin was significantly higher in heart failure patients who died from cardiovascular causes during 3-year follow-up (n=99) compared to survivors (n=99).
Turkieh, Annie; Fertin, Marie; Bouvet, Marion; Mulder, Paul; Drobecq, Hervé; Lemesle, Gilles; Lamblin, Nicolas; de Groote, Pascal; Porouchani, Sina; Chwastyniak, Maggy; Beseme, Olivia; Amouyel, Philippe; Mouquet, Frédéric; Balligand, Jean-Luc; Richard, Vincent; Bauters, Christophe; Pinet, Florence ·