RPEP-07396 · 2023Both SGLT2 inhibitors and GLP-1 receptor agonists have shown significant reductions in major adverse cardiovascular events (MACE) in type 2 diabetes patients with cardiovascular risk. However, patients with peripheral artery disease (PAD) have been consistently underrepresented in these trials. Notably, one major canagliflozin trial showed a signal of increased amputation risk, raising specific concerns for the PAD population.
The review found that while cardiovascular benefits appear to extend to PAD patients based on limited subgroup analyses, dedicated PAD-focused trial data for both drug classes remains scarce.
Skeik, Nedaa; Elejla, Sewar A; Sethi, Anish; Manunga, Jesse; Mirza, Aleem ·
RPEP-07399 · 2023GLP-1 receptor agonists provide cardiovascular protection through multiple mechanisms: improved insulin secretion and action, weight loss, blood pressure lowering, improved lipid profiles, and direct beneficial effects on the heart and blood vessels. These are combined with anti-inflammatory and antioxidant properties that produce robust, consistent reductions in atherothrombotic events, particularly in type 2 diabetes patients with established cardiovascular disease.
The review also highlights that upcoming dual (GIP/GLP-1) and triple incretin receptor agonists may further expand cardiovascular protection possibilities. The evidence has led professional societies to formally recommend GLP-1 RAs for cardiovascular risk reduction in type 2 diabetes.
Solini, Anna; Tricò, Domenico; Del Prato, Stefano · Review
RPEP-07404 · 2023By co-expressing cryptdins with human alpha-lactalbumin in the Origami B E. coli strain to promote inclusion body formation through erroneous intermolecular disulfide bonds, all six cryptdin isoforms were successfully produced, refolded, and purified. The key biological finding was that despite showing no significant structural differences by circular dichroism analysis, each Crp isoform exhibited completely different trends in antimicrobial activity against Gram-positive and Gram-negative bacteria. This functional divergence among structurally similar peptides was unexpected.
Song, Yuchi; Wang, Yi; Yan, Shaonan; Nakamura, Kiminori; Kikukawa, Takashi; Ayabe, Tokiyoshi; Aizawa, Tomoyasu ·
RPEP-07406 · 2023Across 15 pediatric RCTs in autism spectrum disorder, Prader-Willi syndrome, and Phelan-McDermid syndrome, intranasal oxytocin showed neuroimaging evidence of modulating reward processing and social-emotional brain areas.
However, clinical results were mixed, with changes in irritability mainly documented as adverse events rather than primary outcomes. The review identifies the lack of established pharmacodynamic and pharmacokinetic models for intranasal oxytocin as a key barrier, along with small sample sizes and inconsistent dosing across studies.
Sorenson, Kennet; Kendall, Emilee; Grell, Hannah; Kang, Minjoo; Shaffer, Christopher; Hwang, Soonjo ·
RPEP-07418 · 2023Researchers developed ionizable polymeric nanoparticles that co-deliver two immune-boosting agents (TLR7/8 and TLR9 agonists) alongside tumor-specific peptide neoantigens to lymph nodes, dramatically enhancing the immune response and tumor killing. These nanovaccines activated a broad range of antigen-presenting cells, generated robust anti-tumor T cell responses with immune memory, reduced tumor immunosuppression, and — critically — significantly enhanced the effectiveness of checkpoint immunotherapy (ICB) in mouse models of colorectal cancer and brain tumors (glioblastoma). This addresses a key limitation of current checkpoint drugs, which only work in a small subset of patients.
Su, Ting; Liu, Xiang; Lin, Shuibin; Cheng, Furong; Zhu, Guizhi · Animal Study
RPEP-07421 · 2023Both dulaglutide and liraglutide effectively reduced blood glucose, improved biochemical markers, and lowered insulin resistance (HOMA-IR) in women with type 2 diabetes over 24 weeks, with no significant difference in efficacy between the two drugs. However, dulaglutide was more cost-effective — lower overall treatment cost and fewer injection-related side effects — while maintaining equivalent cost-effectiveness ratios.
Su, Yu; Zhang, Shuo; Wu, Zezhen; Liu, Weiting; Chen, Jingxian; Deng, Feiying; Chen, Fengwu; Zhu, Dan; Hou, Kaijian ·
RPEP-07427 · 2023The review identifies three main categories of peptide amphiphiles — amphiphilic peptides, lipidated peptide amphiphiles, and supramolecular peptide amphiphile conjugates — each with distinct design rules governing self-assembly into nanostructures (micelles, vesicles, ribbons, nanofibers). These structures closely resemble native extracellular matrix and have shown promise as tissue engineering scaffolds for bone, cartilage, and neural tissue regeneration in both in vitro and in vivo studies. The review also discusses 3D bio-fabrication strategies for creating PA hydrogels.
Sun, Weizhen; Gregory, David Alexander; Zhao, Xiubo ·
RPEP-07431 · 2023After 30+ years of research, cell-penetrating peptides (CPPs) remain one of the most versatile delivery vehicles for macromolecular drugs. The review identifies key optimization strategies: enhanced endosomal escape (overcoming intracellular trapping), extended blood circulation half-life, improved targeting efficiency through tissue-specific modifications, and stimuli-responsive designs that activate only under specific conditions (pH, enzymes, temperature). Clinical trials of CPP-based delivery systems have been conducted, and the review extracts the critical success factors from these trials.
Sun, Zhe; Huang, Jinhai; Fishelson, Zvi; Wang, Chenhui; Zhang, Sihe ·
RPEP-07435 · 2023The resistant starch meal (rice cooked with coconut oil, M2) produced significantly lower postprandial glucose (p<0.01 for multiple measures) and insulin values (p<0.05) compared to plain rice (M1) in obese children. Postprandial ghrelin — the 'hunger hormone' peptide — was significantly higher after plain rice compared to the coconut oil + lentils meal (M3, p<0.05), suggesting greater appetite suppression with the combined meal.
However, the gut peptide hormones GLP-1 and PYY showed no significant differences between the three meals, and median satiety scores were also not significantly affected, indicating that the metabolic benefits occurred independently of these appetite-regulating peptides.
Suntharesan, Jananie; Atapattu, Navoda; Jasinghe, Eresha; Ekanayake, Sagarika; de Silva, Delpachitra Acharige Gajabahu Harendra; Dunseath, Gareth; Luzio, Steohan; Premawardhana, Lakdasa ·
RPEP-07443 · 2023Among 11 oxytocin-based peptide modifications tested:
- Native oxytocin's disulfide bond cyclization provided improved stability in a human colon model compared to a linear derivative
- Chloroacetyl cyclization increased stability at 1.5h by 30.0%
- Three D-amino acid substitutions (at Tyr, Ile, Leu) improved stability by 58.2% in linear and 79.1% in cyclic structures
- Thioether and N-terminal acetylated cyclizations offered no additional protection
- Three D-AA substitutions in cyclic oxytocin significantly increased permeability across rat colonic tissue, likely by favorably altering secondary structure
- The site and number of D-AA substitutions were critical for stability
Taherali, Farhan; Chouhan, Nerisha; Wang, Fanjin; Lavielle, Sebastien; Baran, Maryana; McCoubrey, Laura E; Basit, Abdul W; Yadav, Vipul ·
RPEP-07449 · 2023Thymosin alpha-1 exerts its immunostimulatory effects by interacting with multiple Toll-like receptors (TLRs) on immune cells. It binds to TLR3, TLR4, and TLR9, activating downstream IRF3 and NF-κB signaling pathways, which promote the proliferation and activation of immune cells. Additionally, Tα1 activates TLR2/NF-κB, TLR2/p38MAPK, and TLR7/MyD88 pathways, stimulating cytokine production that enhances both innate and adaptive immune responses.
This multi-pathway activation explains why Tα1 is effective across different viral infections — it broadly strengthens immune surveillance and response rather than targeting a single mechanism.
Tao, Nana; Xu, Xie; Ying, Yuyuan; Hu, Shiyu; Sun, Qingru; Lv, Guiyuan; Gao, Jianli ·
RPEP-07460 · 2023The combination of capecitabine plus temozolomide (CAPTEM) and 177Lu-DOTATATE peptide receptor radionuclide therapy (PRRT) achieved both symptom control and tumor shrinkage in a patient with heavily pretreated metastatic insulinoma. The patient had previously failed sunitinib, everolimus, lanreotide, and streptozocin plus 5-fluorouracil.
After starting the combined regimen, the frequency of hypoglycemic attacks decreased sufficiently to eliminate the need for daily intravenous glucose infusions, allowing hospital discharge on day 58. CT imaging at 8 months confirmed ongoing shrinkage of both the primary pancreatic tumor and metastatic lesions, with no major adverse events reported.
Terashima, Takeshi; Yamashita, Tatsuya; Takemura, Naoki; Inaki, Anri; Shimizu, Akinori; Harada, Kenichi; Yamashita, Taro; Kinuya, Seigo; Hanada, Keiji ·
RPEP-07463 · 2023Zebrafish exposed to the antibiotic enrofloxacin at environmentally realistic levels (60 μg/L for 28 days) developed anxiety-like behaviors in two standard behavioral tests. The antibiotic disrupted the gut microbiome by increasing Bacteroidetes and lowering the Firmicutes/Bacteroidetes ratio, while significantly altering multiple peptide signaling molecules: intestinal GLP-1, 5-HT, IL-6, and TNF-α were elevated, plasma ACTH and cortisol were reduced, and brain levels of CRH, BDNF, and neuropeptide Y were increased — suggesting the microbiota-gut-brain axis mediated the behavioral changes.
Tian, Dandan; Shi, Wei; Yu, Yihan; Zhou, Weishang; Tang, Yu; Zhang, Weixia; Huang, Lin; Han, Yu; Liu, Guangxu · Animal
RPEP-07465 · 2023The study found that humanized amyloid-beta knockin mice develop concurrent plasma ghrelin elevation and hippocampal ghrelin receptor (GHSR) desensitization as disease progresses. Crucially, the researchers demonstrated that the ghrelin elevation is not a compensatory response to receptor dysfunction. Instead, chronic overstimulation by elevated ghrelin drives enhanced receptor internalization, causing the receptors to become desensitized. This creates a vicious cycle: rising ghrelin leads to receptor shutdown, resulting in hippocampal ghrelin resistance and synaptic injury.
Tian, Jing; Du, Eric; Jia, Kun; Wang, Tienju; Guo, Lan; Zigman, Jeffrey M; Du, Heng ·
RPEP-07466 · 2023Using 13C/15N-labeled BPC-157 combined with UHPLC-HRMS, the researchers constructed a workflow for automatic isotope pair picking and identified nine metabolites from two incubation models. Eight metabolites were produced through conventional amide-bond breaking, while one was generated by a novel metabolic pathway not previously described for BPC-157.
A validated detection method for BPC-157 and its five main metabolites in human urine achieved detection limits of 0.01–0.11 ng/mL, with excellent linearity across a range of 0.02–50 ng/mL (R² > 0.999) and recovery rates above 90%. This provides improved targets for anti-doping control.
Tian, Tian; Jing, Jing; Li, Yuanyuan; Wang, Yang; Deng, Xiaojun; Shan, Yuanhong ·
RPEP-07476 · 2023Clinical studies show GLP-1 receptor agonists in NAFLD improve: liver function tests (ALT/AST), hepatic steatosis (fat accumulation) on histology, and hepatic inflammation on histology. However, they have not demonstrated improvement in liver fibrosis. The review suggests two key directions: early use in non-fibrotic NAFLD to prevent fibrosis progression, and combination therapy with other medications for advanced disease where additive or synergistic effects may be possible.
Tsiampali, Chara; Papaioannidou, Paraskevi; Goulas, Antonis; Polyzos, Stergios A ·
RPEP-07478 · 2023This trilateral scientific statement from the European, American, and Japanese heart failure societies provides a comprehensive framework for how natriuretic peptides — specifically BNP and NT-proBNP — should be used in diagnosing and managing heart failure. The document covers four major areas: the biology and cardiovascular protective effects of natriuretic peptides; their established role as diagnostic and prognostic biomarkers in both acute and chronic heart failure; their use as endpoints in clinical trials and as guides for therapy adjustment; and their direct therapeutic applications through drugs like nesiritide (recombinant BNP), carperitide (ANP), and ARNIs (sacubitril/valsartan).
The statement emphasizes that with the development of ARNIs — which work by preventing the breakdown of natriuretic peptides — these peptides have gained importance not just as biomarkers but as therapeutic agents in their own right.
Tsutsui, Hiroyuki; Albert, Nancy M; Coats, Andrew J S; Anker, Stefan D; Bayes-Genis, Antoni; Butler, Javed; Chioncel, Ovidiu; Defilippi, Christopher R; Drazner, Mark H; Felker, G Michael; Filippatos, Gerasimos; Fiuzat, Mona; Ide, Tomomi; Januzzi, James L; Kinugawa, Koichiro; Kuwahara, Koichiro; Matsue, Yuya; Mentz, Robert J; Metra, Marco; Pandey, Ambarish; Rosano, Giuseppe; Saito, Yoshihiko; Sakata, Yasushi; Sato, Naoki; Seferovic, Petar M; Teerlink, John; Yamamoto, Kazuhiro; Yoshimura, Michihiro · Consensus Statement
RPEP-07479 · 2023This trilateral scientific statement from three major heart failure societies provides a comprehensive framework for natriuretic peptides (BNP and NT-proBNP) in heart failure management. Key roles include: (1) BNP/NT-proBNP as the primary diagnostic biomarkers for heart failure with complementary prognostic value, (2) natriuretic peptide-guided therapy to optimize treatment, and (3) therapeutic applications including nesiritide (recombinant BNP), carperitide (ANP), and angiotensin receptor-neprilysin inhibitors (ARNIs like sacubitril/valsartan) that work by increasing endogenous natriuretic peptide levels.
Tsutsui, Hiroyuki; Albert, Nancy M; Coats, Andrew J S; Anker, Stefan D; Bayes-Genis, Antoni; Butler, Javed; Chioncel, Ovidiu; Defilippi, Christopher R; Drazner, Mark H; Felker, G Michael; Filippatos, Gerasimos; Fiuzat, Mona; Ide, Tomomi; Januzzi, James L; Kinugawa, Koichiro; Kuwahara, Koichiro; Matsue, Yuya; Mentz, Robert J; Metra, Marco; Pandey, Ambarish; Rosano, Giuseppe; Saito, Yoshihiko; Sakata, Yasushi; Sato, Naoki; Seferovic, Petar M; Teerlink, John; Yamamoto, Kazuhiro; Yoshimura, Michihiro ·
RPEP-07480 · 2023In this post-hoc analysis from the AWARD-7 trial, the GLP-1 agonist dulaglutide showed biomarker evidence of reducing kidney fibrosis compared to insulin glargine in type 2 diabetes patients with CKD. Specifically:
- Serum PRO-C6 (a marker of new scar tissue formation — type VI collagen) decreased with dulaglutide but increased with insulin glargine at both 26 and 52 weeks (p<0.01)
- Urine C3M (a marker of scar tissue breakdown — type III collagen degradation) increased with dulaglutide but decreased with insulin glargine (p<0.05)
This combination — less new fibrosis plus more scar tissue clearance — suggests dulaglutide may actively reverse kidney scarring, not just slow its progression. The effects were more pronounced in patients with macroalbuminuria (severe kidney damage). Both fibrosis biomarkers correlated with kidney function (eGFR), supporting their clinical relevance.
Tuttle, Katherine R; Wilson, Jonathan Matthew; Lin, Yanzhu; Qian, Hui-Rong; Genovese, Federica; Karsdal, Morten Asser; Duffin, Kevin L; Botros, Fady T · Post Hoc Analysis
RPEP-07484 · 2023Researchers developed a peptide-based tolerizing vaccine using a galactosylated collagen type II peptide bound to an MHC class II protein (Aq-galCOL2) that directly interacts with disease-driving T cells in autoimmune arthritis. The vaccine expanded a special population of VISTA-positive regulatory T cells that suppressed the autoimmune attack.
Critically, the therapeutic effect was dominant — meaning the protective regulatory T cells could be transferred to other mice and still suppress arthritis. The approach also proved tissue-specific, working across multiple arthritis models including antibody-induced arthritis. This represents a fundamentally different strategy from current arthritis treatments, which broadly suppress the immune system rather than targeting only the disease-causing cells.
Urbonaviciute, Vilma; Romero-Castillo, Laura; Xu, Bingze; Luo, Huqiao; Schneider, Nadine; Weisse, Sylvia; Do, Nhu-Nguyen; Oliveira-Coelho, Ana; Fernandez Lahore, Gonzalo; Li, Taotao; Sabatier, Pierre; Beusch, Christian M; Viljanen, Johan; Zubarev, Roman A; Kihlberg, Jan; Bäcklund, Johan; Burkhardt, Harald; Holmdahl, Rikard · Preclinical
RPEP-07486 · 2023A 44-year-old perimenopausal woman with type 2 diabetes, who had previously been unable to tolerate metformin and semaglutide, experienced significant vaginal hemorrhage beginning one week after receiving her second dose of dulaglutide.
The bleeding was severe enough to cause a significant drop in hemoglobin concentration. Upon discontinuation of dulaglutide, the vaginal bleeding stopped, establishing a temporal relationship between the drug and the adverse event.
This represents a rare, previously unreported side effect of dulaglutide not identified during clinical trials.
Vaccaro, Christopher J; Zaidi, Syed Muhammad Hussain; Iskander, Peter A; McFadden, Erin ·
RPEP-07489 · 2023Encapsulation of antimicrobial peptides SAAP-148 and Ab-Cath in oleyl-modified hyaluronic acid (OL-HA) nanogels maintained their antimicrobial activity against drug-resistant Staphylococcus aureus and Acinetobacter baumannii while significantly reducing toxicity to human cells.
The selectivity index improved 2-fold for SAAP-148 and 16.8-fold for Ab-Cath. Ab-Cath-loaded nanogels achieved a selectivity index of ≥300 for S. aureus and ≥3,000 for A. baumannii — levels that indicate strong clinical potential. The nanogels were 181-206 nm in size with 53-63% encapsulation efficiency.
van Gent, Miriam E; Klodzinska, Sylvia N; Drijfhout, Jan Wouter; Nielsen, Hanne M; Nibbering, Peter H ·
RPEP-07492 · 2023A 73-year-old man with metastatic pancreatic neuroendocrine tumor had both PET-positive and PET-negative liver metastases on 68Ga-DOTATATE PET/CT. Biopsy of a PET-negative lesion confirmed well-differentiated (G2) metastasis with high somatostatin receptor expression, indicating the scan had produced a false-negative result.
After initiating peptide receptor radionuclide therapy with 177Lu-DOTATATE (Lutathera), post-therapeutic scintigraphy revealed vigorous uptake of the therapeutic peptide even in the previously PET-negative liver metastases. Follow-up PET/CT demonstrated partial response to therapy across the treated lesions.
Ventura, David; Roll, Wolfgang; Kasper, Hans-Udo; Rahbar, Kambiz; Stegger, Lars ·
RPEP-07496 · 2023A cell-penetrating peptide (CPP) based delivery system successfully delivered CDNF gene therapy directly into the brains of mice with Parkinson's-like disease, preventing both motor and cognitive dysfunction. The delivery vehicle — a modified rabies virus glycoprotein peptide (mRVG9R) with an Asn194Lys mutation that improves cell penetration — carried the CDNF gene into the striatum, where it protected dopaminergic neurons and oligodendrocytes from paraquat-induced toxicity.
The gene therapy also inhibited astrogliosis and microglial activation (brain inflammation), safeguarding the entire nigrostriatal pathway. Injections on days 0 and 20 were sufficient to protect against 6 weeks of paraquat-induced neurodegeneration.
Villa-Cedillo, Sheila A; Matta-Yee-Chig, Daniel; Soto-Domínguez, Adolfo; Rodríguez-Rocha, Humberto; García-García, Aracely; Montes-de-Oca-Saucedo, Carlos R; Loera-Arias, María de Jesús; Valdés, Jesús; Saucedo-Cárdenas, Odila · Animal Study
RPEP-07502 · 2023PACAP and VIP act through three receptors (VPAC1R, VPAC2R, PAC1R) distributed in both the central nervous system and gastrointestinal tract to regulate appetite, satiety, calorie intake, energy expenditure, and fat accumulation. The review synthesizes evidence showing these peptides modulate body phenotype, metabolism, and homeostatic functions through both central (brain) and peripheral (gut, immune) pathways. Their widespread distribution and multi-organ effects position them as potential therapeutic targets for obesity and metabolic syndrome.
Vu, John P; Luong, Leon; Sanford, Daniel; Oh, Suwan; Kuc, Alma; Pisegna, Rita; Lewis, Michael; Pisegna, Joseph R; Germano, Patrizia M ·
RPEP-07506 · 2023MOTS-c is a peptide encoded by mitochondrial DNA (specifically within the 12S rRNA gene) that acts as a signaling molecule between mitochondria and the cell nucleus. When activated by stress or exercise, MOTS-c moves to the nucleus and turns on genes with antioxidant response elements (ARE) that help cells adapt to stress.
Its primary mechanism involves the Folate-AICAR-AMPK pathway — the same master energy-sensing pathway activated by exercise and the diabetes drug metformin. Through this pathway, MOTS-c influences energy metabolism, insulin sensitivity, inflammation, exercise response, and multiple age-related diseases. The review positions MOTS-c as a key molecule for maintaining the balance between energy production and stress resistance that deteriorates during aging.
Wan, Wei; Zhang, Lieliang; Lin, Yue; Rao, Xiuqing; Wang, Xifeng; Hua, Fuzhou; Ying, Jun · Review
RPEP-07510 · 2023Hypermethylation (epigenetic silencing) of the thymosin β4 (Tβ4) gene was significantly more common in patients with acute-on-chronic hepatitis B liver failure (ACHBLF) compared to those with pre-liver failure, chronic hepatitis B, or healthy controls. Tβ4 mRNA expression showed the opposite pattern — lower in more severe disease. The 3-month mortality rate was significantly higher in patients with methylated Tβ4 than unmethylated.
Critically, Tβ4 methylation status outperformed the MELD score — the standard clinical tool — for predicting 1-, 2-, and 3-month disease incidence. Its predictive value was particularly strong for early and mid-stage liver failure, though not for advanced-stage disease.
Wang, He; Yin, Yan-Ping; Wang, Zhen-Li; Qian, Yu; Fan, Yu-Chen; Liu, Hui-Hui; Wang, Kai · Observational
RPEP-07516 · 2023In vivo, 8 weeks of exenatide treatment regulated most metabolic abnormalities in diabetic rat kidneys as shown by NMR-based metabolomics. In vitro, exendin-4 restored mitochondrial functions in mesangial cells damaged by high-fat/high-glucose conditions: improved antioxidant capacity, increased the Bcl-2/Bax ratio (favoring cell survival over death), reduced cytochrome c release and caspase-3 activation (markers of programmed cell death). Energy metabolism was restored through increased succinate dehydrogenase and phosphofructokinase activities, increased glucose consumption, and inhibition of pyruvate dehydrogenase E1 activity.
Wang, Linxi; Chen, Zhou; Liu, Xiaoying; Wang, Lijing; Zhou, Yu; Huang, Jingze; Liu, Zhiqing; Lin, Donghai; Liu, Libin ·
RPEP-07520 · 2023Adding once-weekly dulaglutide 1.5 mg to basal insulin glargine produced a 2.0% reduction in HbA1c from baseline at 28 weeks, compared to 1.1% with insulin glargine plus placebo — a highly significant difference of 1.0% (p<0.001). Notably, 75.9% of patients in the dulaglutide group achieved the target HbA1c below 7.0%, versus only 33.8% with placebo.
Dulaglutide also produced weight loss while the placebo group gained weight (difference: -1.2 kg, p<0.001), and fasting blood sugar dropped further with dulaglutide (difference: -0.8 mmol/L, p<0.001). Critically, hypoglycemia rates were similar between groups (29.2% vs. 31.3%), and no severe hypoglycemia events occurred in either group.
Wang, Weimin; Yan, Xin; Cheng, Zhifeng; Zhang, Qiqi; Wang, Rui; Deng, Yuying; Ma, Jianhua; Zhu, Dalong · Randomized Controlled Trial
RPEP-07521 · 2023Thymosin β4 was identified in serum by MALDI-TOF mass spectrometry and validated in 540 subjects (274 HCC, 119 cirrhosis, 89 hepatitis, 58 healthy). Serum Tβ4 was significantly elevated in HCC patients. Diagnostic performance: AUROC for Tβ4 was 0.908 (95% CI 0.880-0.935) versus AFP at 0.712 (95% CI 0.662-0.762), with optimal cutoff at 1063.6 ng/mL. Elevated Tβ4 was significantly associated with tumor size (p=0.016) and vascular invasion (p=0.005). Survival was significantly shorter in Tβ4-positive patients (p<0.001). Cox regression confirmed Tβ4 as an independent prognostic factor.
Wang, Wen-Chao; Zhang, Xiao-Feng; Tang, Er-Jiang; Li, A-Jian; Chen, Lei; Wang, Jia-Qi; Ma, Jun-Yong; Zhang, Xiao-Feng; Sun, Bin ·
RPEP-07522 · 2023The review identified 27 amphibian-derived peptides with wound-healing properties: 25 from frogs and 2 from salamanders (tylotoin and TK-CATH). These peptides range from 5-80 amino acid residues in length and have various structural features:
- 9 peptides have intramolecular disulfide bonds (including tiger17, cathelicidin-NV, cathelicidin-DM, RL-QN15)
- 7 peptides are amidated at the C-terminus (including temporin A, temporin B, esculentin-1a)
- The remainder are linear peptides without modifications
All peptides efficiently accelerated wound healing or photodamage repair in animal models. Their mechanisms include promoting keratinocyte and fibroblast proliferation and migration, recruiting neutrophils and macrophages to wounds, and regulating immune responses. Notably, 6 peptides (MSI-1, Pse-T2, cathelicidin-DM, brevinin-2Ta, brevinin-2PN, DMS-PS2) were antimicrobial peptides that also promoted healing of infected wounds by clearing bacteria.
Wang, Xiakun; Duan, Hongcheng; Li, Min; Xu, Wei; Wei, Lin ·
RPEP-07529 · 2023In mice with LPS-induced sepsis (15 mg/kg), dulaglutide (0.6 mg/kg daily) produced multiple protective effects in the lungs:
- Improved weight loss and reduced overall lung injury
- Reversed increases in six inflammatory mediators: IL-1β, TNF-α, IL-6, CXCL1, CCL2, and CXCL2
- Reduced neutrophil and macrophage infiltration in lung tissues
- Reversed apoptosis markers: reduced caspase-3, cleaved caspase-3, caspase-8 expression; restored Bcl-2/Bax ratio; reduced TUNEL-positive (dying) cells
- Reduced expression of P-STAT3 (phosphorylated STAT3) and NLRP3 inflammasome — identified as potential therapeutic targets for sepsis lung injury
These results demonstrate dual anti-inflammatory and anti-apoptotic mechanisms of GLP-1 receptor activation in acute lung injury.
Wang, Yue; Deng, Fengyi; Zhong, Xing; Du, Yijun; Fan, Xingyu; Su, Hong; Pan, Tianrong ·
RPEP-07530 · 2023Researchers engineered a probiotic bacterium (Lactobacillus reuteri) to produce and secrete ShK-235, a peptide that blocks the Kv1.3 potassium channel on inflammatory T cells. When fed to rats, a single oral dose delivered enough functional peptide into the bloodstream to reduce skin inflammation, and daily oral dosing dramatically reduced disease severity in a rat model of rheumatoid arthritis. The peptide did not trigger an immune response against itself, suggesting the probiotic delivery approach avoids the immunogenicity problems that plague many injected peptide drugs.
Wang, Yuqing; Zhu, Duolong; Ortiz-Velez, Laura C; Perry, Jacob L; Pennington, Michael W; Hyser, Joseph M; Britton, Robert A; Beeton, Christine · Animal Study
RPEP-07534 · 2023Thymosin β4 (Tβ4) was downregulated in bile duct ligation (BDL) fibrotic mice and TGF-β1-induced LX-2 hepatic stellate cells. Tβ4 overexpression via lentiviral vectors: inhibited liver fibrosis in BDL mice (confirmed by HE and Masson staining), suppressed stellate cell migration and proliferation in TGF-β1-induced LX-2 cells, reduced ROS production, and blocked MAPK/NF-κB pathway activation (confirmed by reduced p-p38, p-ERK, p-JNK, and nuclear p65). Adding a MAPK activator (U-46619) reversed Tβ4's protective effects, while a MAPK inhibitor (SB203580) mimicked them — both in vitro and in vivo.
Wang, Zilin; Zhang, Ya; Wang, Yinghui; Mou, Qiuju; Ren, Tingting; Zhu, Lili ·
RPEP-07538 · 2023Bulevirtide, a first-in-class peptide entry inhibitor, significantly reduced hepatitis D virus (HDV) RNA levels when combined with tenofovir over 24 weeks. At the primary endpoint, 54% of patients on 2 mg bulevirtide, 50% on 5 mg, and 77% on 10 mg achieved either undetectable HDV RNA or a ≥2 log decline, compared to only 3% on tenofovir alone.
The 10 mg dose showed the strongest antiviral activity with a median 2.03 log10 decline in HDV RNA. However, HDV RNA rebounded after stopping bulevirtide, indicating the need for longer treatment. The drug was generally well tolerated, with asymptomatic bile salt increases being the most common side effect. No treatment-related deaths occurred.
Wedemeyer, Heiner; Schöneweis, Katrin; Bogomolov, Pavel; Blank, Antje; Voronkova, Natalia; Stepanova, Tatiana; Sagalova, Olga; Chulanov, Vladimir; Osipenko, Marina; Morozov, Viacheslav; Geyvandova, Natalia; Sleptsova, Snezhana; Bakulin, Igor G; Khaertynova, Ilsiyar; Rusanova, Marina; Pathil, Anita; Merle, Uta; Bremer, Birgit; Allweiss, Lena; Lempp, Florian A; Port, Kerstin; Haag, Mathias; Schwab, Matthias; Zur Wiesch, Julian Schulze; Cornberg, Markus; Haefeli, Walter E; Dandri, Maura; Alexandrov, Alexander; Urban, Stephan · Randomized Controlled Trial
RPEP-07548 · 2023In 141 patients with metastatic neuroendocrine tumors undergoing peptide receptor radionuclide therapy (PRRT) with [177Lu]Lu-DOTATOC, rising alkaline phosphatase (ALP) levels during treatment were associated with significantly worse outcomes. Patients whose ALP decreased by more than 10% during PRRT had a median progression-free survival (PFS) of 24.3 months, compared to just 12.5 months for those whose ALP increased by more than 10%.
Progression, relapse, or death occurred in 103 of 141 patients (73%). Significant ALP differences between patients with low vs. high PFS were detectable before the third and fourth treatment cycles, suggesting ALP could serve as an early warning marker during PRRT.
Wetz, Christoph; Ruhwedel, Tristan; Schatka, Imke; Grabowski, Jane; Jann, Henning; Metzger, Giulia; Galler, Markus; Amthauer, Holger; Rogasch, Julian M M · Retrospective
RPEP-07549 · 2023In this phase 2 NEJM trial, the oral GLP-1 pill orforglipron produced up to 14.7% body weight loss at 36 weeks in adults with obesity — compared to just 2.3% with placebo. At the highest dose (45 mg), 75% of participants lost at least 10% of their body weight. The drug also improved all prespecified cardiometabolic measures. Gastrointestinal side effects were the main issue, causing 10-17% of participants to discontinue, but these were mostly mild-to-moderate and occurred during the dose ramp-up period.
Wharton, Sean; Blevins, Thomas; Connery, Lisa; Rosenstock, Julio; Raha, Sohini; Liu, Rong; Ma, Xiaosu; Mather, Kieren J; Haupt, Axel; Robins, Deborah; Pratt, Edward; Kazda, Christof; Konig, Manige ·
RPEP-07551 · 2023Tirzepatide is a synthetic 39-amino-acid peptide based on the GIP sequence that acts as a dual GIP and GLP-1 receptor agonist. Across the SURPASS phase 3 trial program, tirzepatide consistently demonstrated significant HbA1c reductions and weight loss benefits as monotherapy and as add-on therapy to various antihyperglycemic drugs. The pharmacokinetics were similar in patients with kidney and hepatic impairment, with metabolites excreted through urine and feces. Common adverse events were gastrointestinal in nature.
Wong, Elaine; Cope, Rebecca; Dima, Lorena; Nguyen, Timothy ·
RPEP-07552 · 2023Three patients with type 1 diabetes and obesity achieved substantial weight loss using a combination of a GLP-1 receptor agonist and pramlintide (an amylin analog). Patient 1 lost 20.9 kg (16.1% of body weight) over 10 months on semaglutide plus pramlintide. Patient 2 lost a total of 21.2 kg (23.1% of body weight) after adding dulaglutide and pramlintide to her regimen. Patient 3 lost 14.6 kg (17.9% of body weight) over 6 months on semaglutide plus pramlintide. All three experienced no significant side effects, needed less insulin, and maintained or improved their HbA1c levels.
Wong, Gunther; Garner, Erica M; Srivastava, Gitanjali · Case Report
RPEP-07557 · 2023From milk fermented with Lactobacillus delbrueckii QS306, researchers identified 27 novel pentapeptides (five amino acids each) with potential angiotensin-converting enzyme inhibitory (ACEI) activity. Of seven tested peptides, three — HLPLP, PYPQR, and VAPFP — showed the best ACE inhibition (lowest IC50 values). However, in vitro digestion simulation significantly reduced their activity, indicating poor stability against gut enzymes.
Molecular docking and dynamics simulations revealed these peptides inhibit ACE through hydrogen bonding and hydrophobic interactions at the enzyme's active site, providing a structural basis for their blood pressure-lowering potential.
Wu, Nan; Wuhanqimuge; Shuang, Quan ·
RPEP-07560 · 2023Using transition metal ion FRET and native ion mobility-mass spectrometry, researchers identified two Cu(II) binding sites in both somatostatin (SST) and octreotide (OCT):
1. Near the disulfide bond — this site initiates self-aggregation of somatostatin, causing the peptide to clump and lose function
2. Complexed by two aromatic residues — this site directly affects the essential motif for receptor binding, impairing SST/OCT interaction with somatostatin receptors
Both binding sites were confirmed by collision-induced dissociation experiments. The structural changes upon copper binding affected both local conformation (FRET distances) and global peptide shape (ion mobility cross-sections).
Wu, Ri; Benzenberg, Lukas R; Svingou, Despoina; Zenobi, Renato ·
RPEP-07573 · 2023All three doses of tirzepatide (5, 10, and 15 mg) showed statistically significant improvements in postprandial glucose, insulin, glucagon, C-peptide, and triglyceride levels compared to dulaglutide 0.75 mg after a standardized meal test at Week 32. Tirzepatide 10 mg and 15 mg also significantly reduced body weight, and all doses significantly reduced body fat mass compared to dulaglutide at Week 52.
These pharmacodynamic differences demonstrate that the dual GIP/GLP-1 agonist tirzepatide has superior metabolic normalization compared to the GLP-1-only agonist dulaglutide across multiple postprandial parameters in Japanese patients with type 2 diabetes.
Yabe, Daisuke; Kawamori, Dan; Seino, Yusuke; Oura, Tomonori; Takeuchi, Masakazu ·
RPEP-07575 · 2023Cell-penetrating peptides (CPPs) have emerged as a versatile drug delivery platform capable of transporting nucleic acids, large proteins, and chemical compounds across cell membranes with low toxicity compared to conventional carriers. The review highlights that combining CPPs with nanoparticles significantly enhances intracellular DNA delivery, and that chemical modifications to CPP structures can improve their cellular uptake efficiency.
While CPPs have demonstrated high efficacy in cellular studies, their translation to in vivo applications remains an active area of research, with long-term side effects and potential toxicity limiting broader clinical implementation.
Yadav, Shikha; Singh, Pratichi ·
RPEP-07591 · 2023Research by Restaino and colleagues demonstrated that tumors across different types, origins, and anatomic locations are densely innervated predominantly by TRPV1+ sensory nerve fibers with likely functional connectivity contributing to increased electrical activity in the tumor bed. The neuropeptide substance P produced by these intratumoral fibers stimulates the neurokinin 1 receptor (NK1R) on tumor cells, driving proliferation and migration. This represents a potentially generalizable molecular pathway mediating cancer-nerve interaction across tumor types.
Ye, Yi; Xie, Tongxin; Amit, Moran ·
RPEP-07596 · 2023Researchers engineered a targeted drug delivery system for ischemic stroke by combining three innovations: (1) using α-mangostin to simultaneously induce mesenchymal stem cell apoptosis and serve as an anti-inflammatory cargo, (2) harvesting the resulting apoptotic vesicles (ApoVs) loaded with both α-mangostin and beneficial protein payloads, and (3) decorating the vesicles with MAP, a matrix metalloproteinase-activatable cell-penetrating peptide that responds to the stroke injury microenvironment.
The MAP-functionalized vesicles targeted the injured ischemic brain after systemic injection and provided enhanced neuroprotection through synergistic effects of the vesicles and α-mangostin. The ApoV protein payloads regulated immune responses, promoted blood vessel formation, and stimulated cell growth — all contributing to brain repair after stroke.
You, Yang; Xu, Jianpei; Liu, Yipu; Li, Haichun; Xie, Laozhi; Ma, Chuchu; Sun, Yinzhe; Tong, Shiqiang; Liang, Kaifan; Zhou, Songlei; Ma, Fenfen; Song, Qingxiang; Xiao, Wenze; Fu, Kaikai; Dai, Chengxiang; Li, Suke; Lei, Jigang; Mei, Qiyong; Gao, Xiaoling; Chen, Jun · Animal And Cell
RPEP-07599 · 2023Researchers developed a "disulfide click" stapling method that converts linear peptides into stable macrocyclic (ring-shaped) forms with improved metabolic stability and ability to enter cells. Using a library of 17 stapling reagents with adjustable lengths and angles, they could bridge peptides from 3 to 18 amino acids long, creating ring structures of 18 to 48 atoms under gentle, biocompatible conditions. The stapled peptides gained anti-cancer activity against HCT-116 colorectal cancer cells (IC50 = 6.81 μM) while the unstapled linear versions had no biological activity. A unique feature: the disulfide staple can be chemically reversed inside cells, releasing the native peptide for intracellular delivery.
Yu, Qing; Bai, Leiyang; Jiang, Xuefeng · In Vitro
RPEP-07606 · 2023Researchers developed a new and efficient method for creating cyclic peptides — ring-shaped peptide molecules that are generally more stable and drug-like than their linear counterparts. Using nucleophilic aromatic substitution (SNAr), they created thioether macrocycles that can be built in solution on unprotected peptides or on resin-bound peptides with side-chain protection in place.
The method's key advantage is that it is "doubly orthogonal" — the chemical reactions used for cyclization don't interfere with standard peptide synthesis chemistry, and the resulting products contain electron-withdrawing groups that can be used for further modifications like adding labels or drug conjugates. Applied to melanocortin receptor targets, the approach generated a library of potent melanocortin agonists with distinct subtype selectivity — meaning different cyclic peptides could preferentially activate specific melanocortin receptor subtypes.
Yue, Wenxiao K; Zhang, Tianxia; Shandre Mugan, Rekha; Barlow, Nicholas; Chalmers, David K; Pouton, Colin W; Thompson, Philip E · Medicinal Chemistry / Drug Design
RPEP-07610 · 2023A patient with metastatic castration-sensitive prostate cancer received two sequential personalized peptide vaccines over 33 months. The first vaccine, containing only HLA class I binding peptides, induced just one CD4+ T-cell response after 21 vaccinations. The second vaccine, incorporating both HLA class I and class II binding peptides, triggered multiple strong and durable CD4+ and CD8+ T-cell responses after only 6 vaccinations. The immune responses were polyfunctional (producing IFNγ, TNF-α, IL-2, and CD154). The patient's PSA remained undetectable for 51 months.
Zelba, Henning; Rabsteyn, Armin; Bartsch, Oliver; Kyzirakos, Christina; Kayser, Simone; Seibold, Marcel; Harter, Johannes; Latzer, Pauline; Hadaschik, Dirk; Battke, Florian; Golf, Alexander; Rettig, Matthew B; Biskup, Saskia ·
RPEP-07612 · 2023Across 9 RCTs with 9,871 participants (6,828 tirzepatide, 3,043 controls), tirzepatide was not associated with a significantly increased risk of pancreatitis (RR 1.46, 95% CI 0.59–3.61, I² = 0.0%).
However, the composite of gallbladder or biliary disease was significantly elevated with tirzepatide compared to placebo or basal insulin (RR 1.97, 95% CI 1.14–3.42, I² = 0.0%). When broken down individually, the risks of cholelithiasis (gallstones), cholecystitis (gallbladder inflammation), and biliary diseases were not individually significant.
Zeng, Qingyue; Xu, Jiao; Mu, Xingyu; Shi, Yi; Fan, Hong; Li, Shuangqing ·
RPEP-07617 · 2023The review covers three generations of CPP development:
1. Natural CPPs: Originally discovered in venoms from snakes, bees, and spiders, these peptides evolved to penetrate cell membranes as part of their toxic function but can be repurposed for drug delivery.
2. Synthetic CPPs: Modern engineering has produced several improved designs:
• Cyclic CPPs with enhanced stability and membrane penetration
• Glycosylated CPPs with improved targeting and reduced toxicity
• D-form CPPs using mirror-image amino acids for protease resistance
3. Therapeutic applications: Various CPPs have been used as vehicles to deliver peptide and protein drugs to cells in preclinical models of diverse diseases, with superior safety and efficiency compared to traditional delivery methods.
Zhang, Huifeng; Zhang, Yanfei; Zhang, Chuang; Yu, Huan; Ma, Yinghui; Li, Zhengqiang; Shi, Nianqiu ·