RPEP-03025 · 2016BPC 157 completely ameliorated symptoms in short-bowel rats across all experimental conditions: surgery alone, surgery plus diclofenac, and surgery plus diclofenac plus the NOS blocker L-NAME. This included protection of anastomosis healing, restoration of intestinal adaptation, and reduction of gastrointestinal, liver, and brain lesions.
The damage cascade was dose-dependent: surgery alone caused mild stomach/duodenum lesions with severe brain lesions; adding diclofenac (12 mg/kg) caused widespread severe lesions across all organs; adding L-NAME on top made everything worse with macro/microscopic necrosis. BPC 157 at both 10 μg/kg and 10 ng/kg reversed all of these. L-arginine only helped reverse L-NAME-specific aggravation.
Lojo, Nermin; Rasic, Zarko; Zenko Sever, Anita; Kolenc, Danijela; Vukusic, Darko; Drmic, Domagoj; Zoricic, Ivan; Sever, Marko; Seiwerth, Sven; Sikiric, Predrag ·
RPEP-03028 · 2016The mitochondria-targeting antioxidant peptide SS-31 (2 mg/day IP for 60 days) significantly reduced right ventricular systolic blood pressure and lung injury in mice with TAC-induced pulmonary arterial hypertension. SS-31 simultaneously improved multiple disease pathways: it decreased oxidative stress (NOX-1/NOX-2), inflammation (MMP-9/TNF-α/iNOS), calcium overload (TRPC channels), apoptosis (BAX/caspase 3/PARP), fibrosis (Smad3/TGF-β), hypoxia signaling (HIF-1α), and DNA damage (γ-H2AX).
Conversely, SS-31 increased antioxidant proteins (HO-1/NQO-1/GR/GPx), anti-fibrotic markers (Smad1/5, BMP-2), small vessel number, and alveolar sacs — demonstrating comprehensive protection of lung tissue architecture and function.
Lu, Hung-I; Huang, Tien-Hung; Sung, Pei-Hsun; Chen, Yung-Lung; Chua, Sarah; Chai, Han-Yan; Chung, Sheng-Ying; Liu, Chu-Feng; Sun, Cheuk-Kwan; Chang, Hsueh-Wen; Zhen, Yen-Yi; Lee, Fan-Yen; Yip, Hon-Kan ·
RPEP-03029 · 2016The hybrid nanoscaffold system composed of (RADA)4 peptide matrix and chitosan/carboxymethyl-β-cyclodextrin nanoparticles successfully encapsulated hydrophobic dexamethasone and exhibited pH-sensitive release. At physiological pH (~7), dexamethasone was released over more than 8 days with distinct kinetic phases, driven by chitosan deprotonation leading to nanoparticle dissociation.
Lu, Lei; Unsworth, Larry D ·
RPEP-03032 · 2016Both substance P (SP) and its receptor NK-1R were expressed at significantly higher levels in endometrial adenocarcinoma tissues and Ishikawa cancer cells compared to normal endometrium.
Substance P treatment significantly enhanced Ishikawa cell proliferation (measured by MTT assay) and invasion through matrigel barriers (transwell assay). Mechanistically, SP induced upregulation of MMP-9 (matrix metalloproteinase 9, which degrades extracellular matrix to enable invasion) and VEGF-C (vascular endothelial growth factor C, which promotes lymphangiogenesis and metastasis). All of these effects were blocked when an NK-1R antagonist was applied.
Ma, Jing; Yuan, Shifa; Cheng, Jianxin; Kang, Shan; Zhao, Wenhong; Zhang, Jie ·
RPEP-03034 · 2016By introducing a second chiral center to a previously described 1,2,4-triazole scaffold, the researchers expanded the chemical diversity of their ghrelin receptor ligand library and extended the molecule's 'C-terminal part' to mimic substance P analog inverse agonists.
Several compounds achieved nanomolar binding affinities at the ghrelin receptor (GHS-R1a) with potent biological activities. One compound demonstrated partial inverse agonist behavior — meaning it not only blocked ghrelin from activating the receptor but actively reduced the receptor's constitutive (basal) signaling. This is pharmacologically significant because the ghrelin receptor has high constitutive activity, which contributes to baseline appetite drive.
Maingot, Mathieu; Blayo, Anne-Laure; Denoyelle, Séverine; M'Kadmi, Céline; Damian, Marjorie; Mary, Sophie; Gagne, Didier; Sanchez, Pierre; Aicher, Babette; Schmidt, Peter; Müller, Gilbert; Teifel, Michael; Günther, Eckhard; Marie, Jacky; Banères, Jean-Louis; Martinez, Jean; Fehrentz, Jean-Alain ·
RPEP-03035 · 2016Retinoic acid (ATRA) upregulated gene expression of both GHRH receptor and ghrelin receptor (GHS-R) in rat pituitary cells, but did not change somatostatin receptor expression. This selectively enhanced the pituitary's responsiveness to the stimulatory peptides GHRH and ghrelin while leaving the inhibitory somatostatin pathway unchanged. ATRA amplified GHRH- and ghrelin-stimulated growth hormone release without affecting basal secretion. Effects were mediated through the RAR-RXR nuclear receptor complex.
Maliza, Rita; Fujiwara, Ken; Tsukada, Takehiro; Azuma, Morio; Kikuchi, Motoshi; Yashiro, Takashi ·
RPEP-03041 · 2016In the landmark SUSTAIN-6 trial, weekly semaglutide reduced the rate of major cardiovascular events (cardiovascular death, nonfatal heart attack, or nonfatal stroke) by 26% compared to placebo in patients with type 2 diabetes at high cardiovascular risk (hazard ratio 0.74; 95% CI 0.58–0.95; P<0.001 for noninferiority). The composite primary endpoint occurred in 6.6% of semaglutide patients versus 8.9% of placebo patients over 104 weeks.
Nonfatal stroke was reduced by 39% (HR 0.61; P=0.04) and nonfatal heart attack by 26% (HR 0.74; P=0.12, not statistically significant). Rates of new or worsening kidney disease were also lower with semaglutide. However, the trial flagged an unexpected safety signal: retinopathy complications were significantly higher with semaglutide (HR 1.76; P=0.02), a finding that required further investigation.
Marso, Steven P; Bain, Stephen C; Consoli, Agostino; Eliaschewitz, Freddy G; Jódar, Esteban; Leiter, Lawrence A; Lingvay, Ildiko; Rosenstock, Julio; Seufert, Jochen; Warren, Mark L; Woo, Vincent; Hansen, Oluf; Holst, Anders G; Pettersson, Jonas; Vilsbøll, Tina · Rct
RPEP-03044 · 2016Adding liraglutide to insulin therapy in type 1 diabetes modestly improved blood sugar control (HbA1c reduced 0.20% more than placebo at the 1.8 mg dose), reduced total insulin requirements by 8%, and produced significant weight loss (up to 4.9 kg at 1.8 mg vs placebo). However, these benefits came with increased rates of symptomatic hypoglycemia across all doses and a significantly higher rate of hyperglycemia with ketosis at the 1.8 mg dose (2.22× higher than placebo).
The safety trade-offs — more low blood sugar episodes and more ketosis events — were judged to limit the clinical usefulness of liraglutide in type 1 diabetes.
Mathieu, Chantal; Zinman, Bernard; Hemmingsson, Joanna Uddén; Woo, Vincent; Colman, Peter; Christiansen, Erik; Linder, Martin; Bode, Bruce · Rct
RPEP-03048 · 2016Nociceptive fibers positive for CGRP, substance P, and TRPV1 were found in all three layers of the rat thoracolumbar fascia (TLF). When inflammation was induced with complete Freund's adjuvant, CGRP- and SP-positive fiber density significantly increased in the inner layer (covering the multifidus muscle) and outer layer, but not the thick middle layer. Electrical stimulation of dorsal roots caused plasma extravasation in the TLF — direct functional evidence that fascia nociceptors can drive neurogenic inflammation.
Mense, Siegfried; Hoheisel, Ulrich ·
RPEP-03052 · 2016In 39 individuals with extreme obesity, 6 months after Roux-en-Y gastric bypass:
- BMI decreased from 44.3 ± 6.4 to 31.7 ± 5.7 kg/m² (P < 0.001)
- Percentage of excess weight lost: 63.2 ± 25.0%
- Leptin and glucose levels decreased significantly (P < 0.001)
- Significant positive correlation between PYY and α-MSH after surgery (r = 0.35, P = 0.004)
- PYY correlated negatively with BMI (r = -0.34, P = 0.002)
- Supports the PYY-to-POMC signal as a mechanism for appetite regulation post-RYGB
Molin Netto, Bárbara Dal; Earthman, Carrie P; Cravo Bettini, Solange; Grotti Clemente, Ana Paula; Landi Masquio, Deborah Cristina; Farias, Gisele; Boritza, Katia; da Silva, Larissa Gabrielle; von der Heyde, Maria Emilia; Dâmaso, Ana Raimunda ·
RPEP-03054 · 2016This review maps out the landscape of peptide receptors on pancreatic beta cells that can be targeted for diabetes treatment. Beyond the well-known GLP-1 receptor, it covers GIP, glucagon, somatostatin, pancreatic polypeptide, CCK, PYY, oxyntomodulin, and ghrelin receptors — all G-protein coupled receptors (GPCRs) that regulate insulin secretion and metabolism.
Critically, the review highlights the emerging strategy of dual and triple agonist peptides that activate two or more of these receptors simultaneously. It also covers fatty acid GPCRs (GPR40, GPR41, GPR43, GPR84, GPR119, GPR120) that regulate peptide hormone secretion and represent additional drug targets.
Moran, Brian M; McKillop, Aine M; O'Harte, Finbarr Pm · Review
RPEP-03057 · 2016The review synthesizes evidence that natriuretic peptide (NP) system deficiency is both associated with and potentially causal of obesity and type 2 diabetes:
- Epidemiological studies show low NP levels predict future T2D risk
- NPs signal through NPRA/cGMP and have direct metabolic effects in fat tissue, muscle, liver, and pancreas
- NPs promote fat oxidation (fat burning), browning of white fat, and insulin secretion
- Obese individuals typically have paradoxically low NP levels, which may perpetuate metabolic dysfunction
- Two degradation pathways — the clearance receptor NPRC and neutral endopeptidases (NEP) — could be targeted to raise circulating NP levels
- Recombinant ANP and BNP already exist as treatments for heart failure and could potentially be repurposed
Moro, Cedric ·
RPEP-03059 · 2016Peptides with strong ACE-inhibitory activity (IC50 = 0.096 g/L) from squid tunics were successfully encapsulated in phosphatidylcholine nanoliposomes with 53% efficiency at an optimal concentration of 1.75 g/L. The liposomes remained stable and maintained their negative zeta potential (~-59 mV) and size (~70 nm) over one week at 4 °C and pH 3-7. Incorporation into fish gelatin did not affect gel properties, and the ACE-inhibitory activity was preserved.
Mosquera, Mauricio; Giménez, Begoña; Montero, Pilar; Gómez-Guillén, Maria Carmen ·
RPEP-03061 · 2016In this randomized, double-blind, placebo-controlled crossover pilot study, 29 males aged 15–40 with ASD and intellectual disabilities received intranasal oxytocin (16 IU/day) or placebo for 8 weeks each. No serious adverse events occurred except one seizure in one participant — an important safety finding given that this population has elevated seizure risk.
Primary outcome (Childhood Autism Rating Scale) and secondary standard scale measures showed no significant difference between oxytocin and placebo. However, exploratory analysis revealed significantly more frequent social interactions during play sessions and daily life in the initial half of the oxytocin-first arm. Plasma oxytocin concentrations significantly correlated with irritability subscale scores on the Aberrant Behavior Checklist, suggesting a biological relationship between oxytocin levels and behavioral symptoms.
Munesue, Toshio; Nakamura, Hiroyuki; Kikuchi, Mitsuru; Miura, Yui; Takeuchi, Noriyuki; Anme, Tokie; Nanba, Eiji; Adachi, Kaori; Tsubouchi, Kiyotaka; Sai, Yoshimichi; Miyamoto, Ken-Ichi; Horike, Shin-Ichi; Yokoyama, Shigeru; Nakatani, Hideo; Niida, Yo; Kosaka, Hirotaka; Minabe, Yoshio; Higashida, Haruhiro ·
RPEP-03065 · 2016CGRP at very low concentrations (-12 M) significantly stimulates Staphylococcus epidermidis virulence by increasing its adherence to keratinocytes and inducing interleukin 8 release, without altering secretion of classical virulence factors. The bacterial DnaK protein acts as the CGRP sensor, and the effects are mediated via MscL mechanosensitive channels, as shown by inhibition with gadolinium chloride.
N'Diaye, Awa R; Leclerc, Camille; Kentache, Takfarinas; Hardouin, Julie; Poc, Cecile Duclairoir; Konto-Ghiorghi, Yoan; Chevalier, Sylvie; Lesouhaitier, Olivier; Feuilloley, Marc G J ·
RPEP-03067 · 2016Three chemiluminescent enzyme immunoassays (CLEIAs) were developed using a novel PEGylation technique to reduce background noise, enabling accurate individual measurement of α-ANP, β-ANP, and proANP directly in plasma.
In patients with acute decompensated heart failure, β-ANP levels showed marked decreases during treatment, while proANP levels decreased only moderately. The ratio of β-ANP to total ANP was significantly lower at discharge compared to admission, whereas α-ANP and proANP ratios remained stable. These distinct patterns suggest β-ANP and proANP may offer complementary biomarker information beyond what BNP alone provides.
Nagai-Okatani, Chiaki; Kangawa, Kenji; Takashio, Seiji; Takahama, Hiroyuki; Hayashi, Tomohiro; Anzai, Toshihisa; Minamino, Naoto ·
RPEP-03068 · 2016Musashi 1 (Msi1) binds to the 3' UTR of TAC1 mRNA in breast cancer cells, competing with microRNAs miR130a and miR206 to stabilize TAC1 mRNA and enhance its translation, thereby promoting tumor growth. Knockdown of Msi1 in breast cancer cells significantly reduced tumor growth in nude BALB/c mice.
Nahas, George R; Murthy, Raghav G; Patel, Shyam A; Ganta, Teja; Greco, Steven J; Rameshwar, Pranela ·
RPEP-03071 · 2016Obese children showed attenuated postprandial ghrelin and peptide YY (PYY) responses compared to healthy-weight children. Ghrelin normally drops after eating (signaling fullness), but this drop was blunted in obese children at both 60 and 120 minutes (p<0.05 for both). Similarly, PYY normally rises after eating (promoting satiety), but this rise was reduced in obese children at both time points. These altered peptide hormone responses suggest a physiological basis for impaired appetite regulation in childhood obesity.
Nguo, K; Walker, K Z; Bonham, M P; Huggins, C E ·
RPEP-03075 · 2016T cell epitope peptide therapy — using carefully selected short peptide fragments from major allergens — has shown encouraging results in randomized, double-blind, placebo-controlled clinical trials. The peptides are designed to bind a wide range of immune system MHC class II molecules, allowing them to induce tolerance across genetically diverse patient populations.
Trials in cat allergy, house dust mite allergy, and grass pollen allergy have demonstrated significant efficacy with short treatment courses. The preferred delivery method is intradermal injection into non-inflamed skin, and adverse events have been inconsequential and non-systemic — a major safety advantage over traditional whole-allergen immunotherapy.
O'Hehir, Robyn E; Prickett, Sara R; Rolland, Jennifer M ·
RPEP-03076 · 2016All reviewed clinical trials confirmed that both single-dose and long-term intranasal oxytocin administration was well tolerated in individuals with ASD, with no severe adverse events reported. However, efficacy results were inconsistent:
- Some studies reported significant improvement in core ASD symptoms including social-communicative deficits after long-term administration
- Other studies showed no such improvement
The review identifies several potential factors influencing outcomes: dosage amount, frequency of administration, and participant characteristics (age, sex, intellectual ability). The authors also highlight unresolved questions about the pharmacokinetics — how intranasal oxytocin actually reaches and affects the central nervous system.
Okamoto, Yuko; Ishitobi, Makoto; Wada, Yuji; Kosaka, Hirotaka ·
RPEP-03078 · 2016Replacing sucrose with the low-calorie bulk sweetener erythritol in test meals did not change post-meal GLP-1 or PYY gut hormone levels, and did not affect how much food people ate afterward or their preference for sweet foods. Both lean and obese participants showed similar gut hormone responses regardless of whether the meal contained sucrose or erythritol.
The one notable difference: when lean participants ate a larger-volume isocaloric erythritol meal, they reported less hunger than after the sucrose control meal (p=0.003) — likely a volume effect rather than a sweetener effect. This volume-related hunger reduction was not seen in obese participants.
Overduin, Joost; Collet, Tinh-Hai; Medic, Nenad; Henning, Elana; Keogh, Julia M; Forsyth, Faye; Stephenson, Cheryl; Kanning, Marja W; Ruijschop, Rianne M A J; Farooqi, I Sadaf; van der Klaauw, Agatha A · Rct
RPEP-03079 · 2016TLR-2, TLR-4, and hBD-1 expression levels differed significantly across all four skin regions examined (epidermis, dermis, inflammation area, and skin appendages) in acne lesions (p<0.05). Cathelicidin levels differed significantly only in the inflammation region.
Specifically, TLR-2 in the epidermis was lower in nodular lesions than in papules and comedones. TLR-2 in the inflammation region and dermis was significantly higher in papules compared to pustules. TLR-4 in the dermis was significantly lower in comedones compared to papules. hBD-1 in the epidermis was significantly higher in comedones compared to nodules. Cathelicidin expression in the inflammation region of comedones was significantly low.
Ozlu, Emin; Karadag, Ayse Serap; Ozkanli, Seyma; Oguztuzun, Serpil; Kilic, Murat; Zemheri, Ebru; Akbulak, Ozge; Akdeniz, Necmettin ·
RPEP-03084 · 2016M2 macrophages contained and released significantly higher amounts of the opioid peptides Met-enkephalin, dynorphin A (1-17), and β-endorphin compared to unstimulated M0 and pro-inflammatory M1 macrophages.
When 5 × 10⁵ M2 macrophages were injected perineurally at the sciatic nerve injury site on days 14 and 15 after chronic constriction injury, they significantly reduced mechanical hypersensitivity following the second injection. This analgesic effect was reversed by perineurally applied naloxone methiodide (an opioid receptor antagonist that doesn't cross the blood-brain barrier), confirming it was mediated by local opioid receptor activation.
Importantly, M2 cells only reduced mechanical pain — not heat hypersensitivity — and had no effect in sham-operated animals. Neither M0 nor M1 macrophages altered pain sensitivity. Fluorescent tracking showed that transferred cells remained at the nerve and maintained their phenotype.
Pannell, Maria; Labuz, Dominika; Celik, Melih Ö; Keye, Jacqueline; Batra, Arvind; Siegmund, Britta; Machelska, Halina ·
RPEP-03086 · 2016Six cathelicidin peptides were characterized in Tasmanian devils. Saha-CATH5 and Saha-CATH6 showed broad-spectrum antibacterial activity, killing methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecalis (VRE). Saha-CATH3 had antifungal activity. Saha-CATH5 and 6 were toxic to human A549 cells at 500 μg/mL — over 7 times the pathogen-killing concentration. All six cathelicidins were widely expressed across immune tissues, digestive tract, respiratory tract, reproductive tract, milk, and pouch lining, indicating broad innate immune roles.
Peel, E; Cheng, Y; Djordjevic, J T; Fox, S; Sorrell, T C; Belov, K ·
RPEP-03092 · 2016In Sprague-Dawley rats treated for 7 days:
- Morphine alone produced pain relief on day 1 that diminished by day 4, indicating tolerance development
- Co-administration of fosaprepitant (30 mg/kg daily) with morphine (10 mg/kg twice daily) attenuated tolerance development (days 1 and 3) and maintained pain relief through days 1-4 compared to controls
- Spinal cord immunohistochemistry showed increased substance P expression in the morphine + fosaprepitant group
- CGRP (calcitonin gene-related peptide) expression was also assessed
- The enhanced analgesia is likely linked to decreased release of substance P from presynaptic terminals in the spinal cord
Prasoon, Pranav; Gupta, Shivani; Kumar, Rahul; Gautam, Mayank; Kaler, Saroj; Ray, Subrata Basu ·
RPEP-03095 · 2016The researchers developed a detailed protocol for building a library of backbone cyclic peptides using microwave-assisted synthesis, which dramatically speeds up the chemical reactions compared to conventional methods. The peptides were designed to target protein-protein interactions in the Leishmania parasite (which causes leishmaniasis) by focusing on sequences conserved in the parasite but absent from the human host.
The library approach is key: all cyclic peptides share the same amino acid sequence but differ in ring size and position, systematically varying the 3D shape. This allows researchers to screen for the most biologically active conformation without needing to predict it computationally — a notoriously difficult problem for cyclic peptides.
Qvit, Nir; Kornfeld, Opher S · Methods Protocol
RPEP-03098 · 2016In wildtype mice, environmental enrichment reduced anxiety and decreased central glucocorticoid receptor expression — classic beneficial effects. In NPY knockout mice, these benefits were completely absent. Instead, NPY-KO mice showed multiple adverse responses to enrichment: altered EE item preferences, exaggerated stress-induced hyperthermia, impaired spatial memory, higher hippocampal BDNF mRNA levels, and altered hippocampal synaptic plasticity.
Molecular and morphological changes were observed in both the amygdala and hippocampus of NPY-KO mice, suggesting NPY normally acts in these brain regions to buffer environmental stimulation. The authors propose that without NPY, the arousal and novelty inherent in enriched environments becomes overwhelming rather than beneficial — converting a positive experience into a negative one.
Reichmann, Florian; Wegerer, Vanessa; Jain, Piyush; Mayerhofer, Raphaela; Hassan, Ahmed M; Fröhlich, Esther E; Bock, Elisabeth; Pritz, Elisabeth; Herzog, Herbert; Holzer, Peter; Leitinger, Gerd ·
RPEP-03099 · 2016Neuropeptide Y (NPY) is a key stress-buffering peptide in the brain with anxiolytic, stress-relieving, and neuroprotective properties. Stress alters NPY production in specific brain regions, with the direction and magnitude varying by stress type and duration.
NPY acts through four receptor subtypes with opposing effects: Y1 receptor activation reduces anxiety while Y2 receptor activation increases it. Higher NPY levels correlate with better stress coping and resilience, while low NPY is linked to PTSD vulnerability and behavioral disruption in animal models. NPY gene polymorphisms in humans predict impaired stress processing and increased neuropsychiatric disease risk. The peptide also shows neuroprotective roles in Alzheimer's, Parkinson's, and Huntington's disease.
Reichmann, Florian; Holzer, Peter · Narrative Review
RPEP-03107 · 2016The review consolidates multiple lines of evidence linking NPY to PTSD:
- NPY is abundantly expressed in forebrain limbic and brainstem areas that regulate stress and emotional behaviors
- Animal studies demonstrate NPY's role in stress responses, anxiety, fear, and autonomic regulation
- Genetic studies associate NPY polymorphisms with stress coping and affect
- CSF measurements in combat veterans provide direct evidence: reduced NPY associates with PTSD diagnosis and symptomology
- NPY is also involved in pain, depression, addiction, and metabolism — all PTSD comorbidities
- The NPY system represents both a biomarker for PTSD risk/diagnosis and a potential therapeutic target
Schmeltzer, Sarah N; Herman, James P; Sah, Renu ·
RPEP-03110 · 2016Despite more than two decades of clinical use, our understanding of natriuretic peptide biochemistry remains incomplete. The circulating forms of natriuretic peptides are far more diverse than initially appreciated, with multiple molecular forms coexisting in plasma. This complexity means that different assays may measure different combinations of these forms, potentially giving inconsistent results.
The simplistic clinical model — that elevated NP values directly indicate heart failure severity and predict prognosis — is insufficient. A deeper understanding of how the NP system works, including the processing, degradation, and clearance of different peptide forms, is needed for correct interpretation of results in cardiovascular practice.
Semenov, Alexander G; Katrukha, Alexey G ·
RPEP-03111 · 2016This systematic review examined 61 in vivo studies on ghrelin, ghrelin-receptor agonists, and ghrelin genetic variants in relation to cancer. Nearly three-quarters (73.8%) of studies found either no statistically significant association or an inverse association between ghrelin and cancer risk, presence, or growth.
Notably, all 11 studies that specifically tested treatment with exogenous ghrelin or ghrelin-receptor agonists reported null or inverse cancer associations. Only 16.7% of all reviewed studies found a positive association, and 10% reported mixed results. Cancer patients tended to have lower serum ghrelin levels than controls for some cancer types, though not all.
Sever, Sakine; White, Donna L; Garcia, José M · Systematic Review
RPEP-03115 · 2016Intraplantar BoNT-B (1 U) reduced carrageenan-induced mechanical allodynia without affecting paw edema, confirming a central rather than local anti-inflammatory mechanism. The toxin decreased spinal phosphorylation of GluA1 (glutamate receptor subunit) at serine 845 and Akt at serine 473, as well as c-Fos expression — all markers of spinal nociceptive facilitation. BoNT-B inhibited NMDA-evoked but not substance P-evoked phosphorylation of GluA1 and Akt in the dorsal horn, demonstrating selective modulation of glutamate-mediated versus tachykinin-mediated spinal pain pathways.
Sikandar, Shafaq; Gustavsson, Ynette; Marino, Marc J; Dickenson, Anthony H; Yaksh, Tony L; Sorkin, Linda S; Ramachandran, Roshni ·
RPEP-03117 · 2016SCA23 mutations in Dynorphin A disrupted the peptide's N-terminal α-helix, a key structural feature needed for κ-opioid receptor binding. This structural change led to decreased opioid receptor affinity.
The R6W and R9C mutations made Dynorphin A markedly resistant to degradation and less soluble, leading to peptide accumulation. R6W and wild-type Dynorphin A were the most toxic to primary cerebellar neurons. For R6W Dynorphin A, this toxicity involved a switch from opioid to NMDA receptor signaling, while wild-type toxicity occurred through a different mechanism. L5S Dynorphin A showed the opposite pattern — increased degradation and no aggregation.
The authors propose that SCA23 pathology results from two converging mechanisms: loss of opioid-mediated neuroprotection and gain of NMDA-mediated excitotoxicity.
Smeets, Cleo J L M; Zmorzyńska, Justyna; Melo, Manuel N; Stargardt, Anita; Dooley, Colette; Bakalkin, Georgy; McLaughlin, Jay; Sinke, Richard J; Marrink, Siewert-Jan; Reits, Eric; Verbeek, Dineke S ·
RPEP-03119 · 2016Repeated binge-like ethanol drinking produced specific changes in melanocortin peptide expression in hypothalamic subregions: α-MSH (the appetite-suppressing peptide) was selectively decreased, while AgRP (the appetite-stimulating peptide) was selectively increased. These changes were specific to ethanol — not seen with sucrose or water controls.
Functional manipulation confirmed the significance: injection of the nonselective melanocortin receptor agonist melanotan-II (MTII) directly into the lateral hypothalamus (LH) significantly reduced binge-like ethanol consumption, while injection of the antagonist AgRP into the same region augmented drinking. These effects were region-specific to the LH, as they were not observed when drugs were delivered to other brain regions.
Sprow, Gretchen M; Rinker, Jennifer A; Lowery-Gointa, Emily G; Sparrow, Angela M; Navarro, Montserrat; Thiele, Todd E ·
RPEP-03120 · 2016BPC 157 at both 10 µg/kg and 10 ng/kg doses completely eliminated succinylcholine-induced hyperkalemia and cardiac arrhythmias in rats. It also markedly attenuated or eliminated behavioral agitation, muscle twitches, motionless resting, and post-succinylcholine hyperalgesia (pain sensitivity).
BPC 157 immediately eliminated leg contractures and counteracted both edema and the decrease in muscle fibers in the diaphragm and tibial muscles. These protective effects were seen whether BPC 157 was given intraperitoneally 30 minutes before succinylcholine, immediately after, or orally in drinking water for 24 hours prior to succinylcholine administration.
Stambolija, Vasilije; Stambolija, Tamara Perleta; Holjevac, Jadranka Katancic; Murselovic, Tamara; Radonic, Jelena; Duzel, Viktor; Duplancic, Bozidar; Uzun, Sandra; Zivanovic-Posilovic, Gordana; Kolenc, Danijela; Drmic, Domagoj; Romic, Zeljko; Seiwerth, Sven; Sikiric, Predrag ·
RPEP-03122 · 2016The minor allele of the rs2948694 SNP in the ghrelin receptor gene (GHSR) was associated with higher AUDIT scores (P = 0.0204, recessive model) and smoking (P = 0.0002, dominant model) in 4,161 Finnish adults. Post hoc analysis showed this risk allele was also associated with increased likelihood of high-level alcohol problems (AUDIT scores ≥ 16; P = 0.0043, recessive model).
Two SNPs in the pre-proghrelin gene (GHRL) — rs4684677 (Gln90Leu) and rs696217 (Leu72Met) — were not significantly associated with alcohol use or smoking outcomes.
Suchankova, Petra; Nilsson, Staffan; von der Pahlen, Bettina; Santtila, Pekka; Sandnabba, Kenneth; Johansson, Ada; Jern, Patrick; Engel, Jörgen A; Jerlhag, Elisabet ·
RPEP-03127 · 2016LL-37, the human antimicrobial peptide known primarily for fighting infections, was found to be significantly overexpressed in the skin of systemic sclerosis (SSc) patients — particularly in the small blood vessels of affected skin. Serum LL-37 levels were significantly higher in SSc patients than in healthy controls, and these levels correlated positively with skin fibrosis severity (skin score), alveolitis activity (lung inflammation), and the presence of digital ulcers. The study identified a molecular mechanism: deficiency of the transcription factor Fli1 drives LL-37 upregulation in endothelial cells, confirmed through gene silencing and chromatin immunoprecipitation. Mouse models of SSc (bleomycin-treated and Fli1+/- mice) showed similar upregulation of CRAMP, the mouse equivalent of LL-37.
Takahashi, T; Asano, Y; Nakamura, K; Yamashita, T; Saigusa, R; Ichimura, Y; Toyama, T; Taniguchi, T; Yoshizaki, A; Tamaki, Z; Tada, Y; Sugaya, M; Kadono, T; Sato, S ·
RPEP-03134 · 2016In a rat model of endometriosis, the condition caused significant changes in the brain's pain-processing center — the periaqueductal gray (PAG). After 60 days of endometriosis, mu opioid receptor (MOR) expression decreased by 20% and NMDA receptor (NR1) profiles decreased by 40% in the ventral PAG, despite no changes in endogenous opioid peptide levels (met-enkephalin, leu-enkephalin, and β-endorphin).
This means endometriosis doesn't reduce the brain's supply of natural painkillers — it reduces the receptors they need to work through. With fewer opioid receptors in the PAG, the brain's natural pain-dampening system becomes less effective, potentially explaining why endometriosis pain is so persistent and difficult to treat.
Torres-Reverón, Annelyn; Palermo, Karylane; Hernández-López, Anixa; Hernández, Siomara; Cruz, Myrella L; Thompson, Kenira J; Flores, Idhaliz; Appleyard, Caroline B · Animal Study
RPEP-03136 · 2016Ba-Wei-Di-Huang-Wan (BWDHW) and its active component loganin dose-dependently inhibited reactive oxygen species (H₂O₂ and HOCl) activity in vitro. In rats, oral pretreatment with BWDHW (250 mg/kg) or loganin (5 mg/kg) twice daily for two weeks significantly suppressed substance P-induced increases in voiding frequency, pelvic afferent nerve activity, NF-κB/ICAM-1 expression, leukocyte infiltration (neutrophils, monocytes/macrophages, and mast cells), and reactive oxygen species levels in the bladder.
The protective effects were mediated through inhibition of substance P/neurokinin-1 receptor signaling, which reduced downstream NF-κB activation, ICAM-1-mediated immune cell adhesion, and oxidative tissue injury.
Tsai, Wen-Hsin; Wu, Chung-Hsin; Cheng, Chen-Hung; Chien, Chiang-Ting ·
RPEP-03137 · 2016Three neuropeptides were significantly elevated in fibromyalgia serum: CRH (0.82 vs 0.49 ng/ml, P = 0.026), substance P (0.39 vs 0.12 ng/ml, P < 0.0001), and hemokinin-1 (7.98 vs 5.71 ng/ml, P = 0.002). SP and HK-1 levels were positively correlated (Pearson r = 0.45, P = 0.002).
Inflammatory cytokines IL-6 (2.97 vs 1.79 pg/ml, P = 0.029) and TNF (0.92 vs 0.69 pg/ml, P = 0.006) were also elevated. Conversely, IL-31 and IL-33 were significantly lower in fibromyalgia patients (P = 0.0001 and P = 0.044). Neurotensin levels showed no difference. The authors connect these findings to their prior work showing CRH and SP stimulate IL-6 and TNF release from mast cells.
Tsilioni, Irene; Russell, Irwin J; Stewart, Julia M; Gleason, Rae M; Theoharides, Theoharis C ·
RPEP-03139 · 2016Washing with common skin cleansers produced small but statistically significant decreases in LL-37 antimicrobial peptide levels on the skin surface shortly after washing. However, no significant changes were detected in bacterial community abundance or diversity. Group A Streptococcus did not survive better on washed skin compared to unwashed skin.
In contrast, soaps containing antimicrobial compounds (benzalkonium chloride or triclocarban) decreased the growth of Group A Streptococcus applied after rinsing, demonstrating that antimicrobial soap additives provide an additional protective effect beyond the mechanical cleaning action.
Two, Aimee M; Nakatsuji, Teruaki; Kotol, Paul F; Arvanitidou, Evangelia; Du-Thumm, Laurence; Hata, Tissa R; Gallo, Richard L ·
RPEP-03140 · 2016Beta-endorphin, an opioid peptide known for pain relief and mood regulation, also triggers the acrosome reaction in human sperm — a critical step required for fertilization. The researchers found that beta-endorphin's precursor protein (pro-opiomelanocortin) is present in the middle section and tail of human sperm and in the seminiferous tubules of the testis. When beta-endorphin was applied to sperm in the lab, it increased the percentage of sperm undergoing the acrosome reaction in an inversely dose-dependent manner (lower doses had a stronger effect) through a calcium-independent protein kinase C pathway — a mechanism distinct from progesterone's effect on sperm.
Urizar-Arenaza, I; Estomba, H; Muñoa-Hoyos, I; Matorras, R; Esposito, A; Candenas, L; Pinto, F M; Valdivia, A; Irazusta, J; Subirán, N · In Vitro
RPEP-03142 · 2016Mid-regional pro-adrenomedullin (MR-proADM) — a stable surrogate marker for the peptide hormone adrenomedullin — is emerging as a superior biomarker for organ failure and mortality risk in sepsis patients. MR-proADM outperformed both procalcitonin (PCT) and C-reactive protein (CRP) for predicting unfavorable outcomes and death in ICU patients with sepsis.
Importantly, MR-proADM levels are independent of the infecting organism — instead, they reflect the magnitude of organ failure itself, making it a severity marker rather than an infection marker. Serial MR-proADM measurements on days 2–5 of ICU admission help identify patients with poor prognosis. The review recommends adding MR-proADM to the standard biomarker panel for critically ill sepsis patients.
Valenzuela-Sánchez, Francisco; Valenzuela-Méndez, Blanca; Rodríguez-Gutiérrez, Juan Francisco; Estella-García, Ángel; González-García, María Ángela · Review
RPEP-03143 · 2016The stevia-derived sweetener rebaudioside A dramatically increased GLP-1 peptide release from mouse intestinal organoids: 1.7-fold in duodenum (p<0.01), 2.2-fold in jejunum (p<0.01), and 4.3-fold in ileum (p<0.001). It also increased PYY release 3-fold in the ileum (p<0.05). Long-term (18-hour) exposure increased expression of enteroendocrine cell markers: chromogranin A 3.5-fold, glucagon 3.5-fold, PYY 3.8-fold, and CCK 6.5-fold (all p<0.05 or better), suggesting rebaudioside A not only stimulates peptide secretion but also promotes enteroendocrine cell differentiation.
van der Wielen, Nikkie; Ten Klooster, Jean Paul; Muckenschnabl, Susanne; Pieters, Raymond; Hendriks, Henk Fj; Witkamp, Renger F; Meijerink, Jocelijn ·
RPEP-03144 · 2016Female users of CJC-1295 on online forums reported using the peptide primarily for weight loss, muscle enhancement, youthful skin, improved sleep, and injury healing. They demonstrated awareness of gender-specific differences in growth hormone pulses affecting dosing and cycling, and expressed concerns about potential long-term health consequences.
Forum users appeared experienced in combining multiple performance and image-enhancing drugs, with CJC-1295 being one product in a broader supplementation regimen.
Van Hout, Marie Claire; Hearne, Evelyn · Qualitative
RPEP-03148 · 2016The ghrelin receptor (GHS-R1a) ligand field has evolved from peptide growth hormone secretagogues derived from Met-enkephalin to a diverse landscape of peptides, peptidomimetics, and small molecules. Several agonists reached clinical trials for growth hormone release, gastric emptying, and cachexia, but only GHRP-2 achieved approval (diagnostic use in Japan). The field has pivoted toward antagonists and inverse agonists targeting obesity and overweight, though none had reached market at the time of review.
Vodnik, M; Štrukelj, B; Lunder, M ·
RPEP-03151 · 2016The self-assembling peptide hydrogel (SAPH) demonstrated mechanical properties matching native human nucleus pulposus tissue and was deliverable via minimally invasive injection. In 3D culture, nucleus pulposus cells showed upregulation of NP-specific genes (KRT8, KRT18, FOXF1), confirming phenotype restoration after de-differentiation. Cell viability remained high throughout culture with a stable viable population. The SAPH stimulated time-dependent increases in aggrecan and type II collagen deposition — two critical extracellular matrix components of healthy disc tissue.
Wan, Simon; Borland, Samantha; Richardson, Stephen M; Merry, Catherine L R; Saiani, Alberto; Gough, Julie E ·
RPEP-03158 · 2016At 4 weeks post-fracture (acute phase), 90% of rats showed pain behaviors (allodynia, unweighting), warmth, edema, and epidermal thickening. Substance P, NK1 receptor, TNFα, IL-1β, IL-6, and nerve growth factor (NGF) were all elevated in sciatic nerve and/or skin. By 16 weeks (chronic phase), only pain behaviors persisted — all peripheral inflammatory markers had returned to normal.
Critically, spinal cord levels of NK1 receptor, TNFα, IL-1β, and NGF remained elevated at both 4 and 16 weeks. Peripheral administration of IL-1 receptor antagonist (anakinra) or anti-NGF blocked pain at 4 weeks but not 16 weeks. However, intrathecal (spinal) delivery of NK1 receptor antagonist, anakinra, or anti-NGF reduced pain at both timepoints, demonstrating that central mechanisms sustain chronic CRPS pain.
Wei, Tzuping; Guo, Tian-Zhi; Li, Wen-Wu; Kingery, Wade S; Clark, John David ·
RPEP-03161 · 2016MENX rats with a p27 mutation developed pancreatic islet hyperplasia with elevated numbers of ghrelin-producing ε-cells, resulting in high plasma levels of both acylated and unacylated ghrelin. These rats showed increased food intake, enhanced body fat mass, and elevated triglycerides and cholesterol — effects confirmed by GHS-R1a antagonist treatment.
Paradoxically, despite obesity, MENX rats showed improved insulin sensitivity and decreased glucose-stimulated insulin secretion. At 7.5 months, hypothalamic GHS-R1a, NPY, and AgRP mRNA levels were decreased, suggesting prolonged high ghrelin may lead to reduced ghrelin signaling effectiveness (desensitization).
Wiedemann, Tobias; Bielohuby, Maximilian; Müller, Timo D; Bidlingmaier, Martin; Pellegata, Natalia S ·
RPEP-03162 · 2016SGLT2 inhibitors and incretin-based therapies (DPP-4 inhibitors and GLP-1 receptor agonists) offer clinically important advantages over older diabetes drugs: weight loss, low hypoglycemia risk, blood pressure reduction, and — for empagliflozin specifically — reduced cardiovascular events in high-risk patients. These drugs may also correct core type 2 diabetes defects by improving β-cell function and insulin sensitivity. However, GLP-1 RAs carry nausea risk, SGLT2i are associated with genital infections, volume depletion, and rare diabetic ketoacidosis, and pancreatitis risk with incretins remains unclear.
Wilding, John P H; Rajeev, Surya Panicker; DeFronzo, Ralph A ·