RPEP-06573 · 2022Across 23 randomized controlled trials involving 22,096 patients with type 2 diabetes, semaglutide was not associated with an overall increased risk of diabetic retinopathy compared to all control groups (RR 1.14, 95% CI 0.98–1.33).
However, the picture changed in subgroup analyses. Compared specifically to placebo, semaglutide was associated with a 24% increased risk of retinopathy (RR 1.24, 95% CI 1.03–1.50). Two patient groups faced the highest risk: those aged 60 or older (RR 1.27) and those with diabetes duration of 10+ years (RR 1.28). There were 730 total retinopathy cases — 463 in semaglutide groups and 267 in control groups.
Wang, Feiyu; Mao, Yinjun; Wang, Hang; Liu, Yiwei; Huang, Pinfang · Meta Analysis
RPEP-06575 · 2022TRAF6-overexpressing dendritic cells showed increased expression of costimulatory molecules, MHC molecules, and IL-12 — all markers of enhanced immune cell maturation and Th1-promoting capacity. When pulsed with MUC1 peptide antigen and administered therapeutically to mice bearing B16-MUC1 melanoma tumors, they significantly inhibited tumor growth compared to control dendritic cells.
The anti-tumor effect was accompanied by increased MUC1-specific Th1 (helper) and Tc1 (cytotoxic/killer) T cell responses, and a decrease in regulatory T cells (Tregs) — a key population that tumors exploit to suppress immunity. This dual effect of boosting anti-tumor immunity while reducing immune suppression makes TRAF6-overexpressing DCs a particularly promising immunotherapy approach.
Wang, Jingjing; Liu, Yu; Ni, Weihua; Wu, Xinjie; Zhou, Jianhong; Zhang, Zenan; Zhou, Hongyue; Zhang, Nannan; Jiang, Mengyu; Sang, Qianyu; Yuan, Hongyan; Tai, Guixiang ·
RPEP-06576 · 2022Soft-shelled turtle peptide (STP) supplementation in Drosophila melanogaster produced multiple anti-aging effects:
- Lifespan extension: 20.23% increase in mean lifespan for males, 9.04% for females
- Healthspan improvements: maintained climbing ability, enhanced gut barrier integrity, improved antioxidant capacity, and increased resistance to starvation and heat stress
- No appetite effect: daily food intake was unchanged, ruling out caloric restriction as the mechanism
Mechanistically, STP enhanced autophagy and reduced oxidative stress by downregulating the TOR signaling pathway. Molecular analysis showed 95.18% of identified peptide sequences could potentially inhibit TOR through hydrogen bonds, van der Waals forces, hydrophobic interactions, and electrostatic interactions.
Wang, Qianqian; Zhang, Junhui; Zhuang, Jiachen; Shen, Fei; Zhao, Minjie; Du, Juan; Yu, Peng; Zhong, Hao; Feng, Fengqin ·
RPEP-06577 · 2022Topical histamine induced significant ocular redness (peaking at 10 minutes) along with increased substance P levels in tears. The NK1R antagonist L-703,606 was effective in two scenarios:
1. Prevention: Applied 10 minutes before histamine, it significantly reduced the ocular redness index (ORI) and suppressed the inflammatory response.
2. Treatment: Applied at peak redness (10 minutes after histamine), it still effectively reduced ORI.
In both cases, L-703,606 suppressed conjunctival blood vessel dilation, decreased eosinophil and neutrophil infiltration, reduced inflammatory cytokine expression, and lowered substance P levels in tears.
Wang, Shudan; Liu, Lingjia; Blanco, Tomas; Ge, Hongyan; Xia, Yutong; Pang, Kunpeng; Chen, Yihe; Dana, Reza ·
RPEP-06583 · 2022From 1 gram of antler bone, 0.14 grams of calcium was extracted. The peptide-calcium chelate rate was 53.68 ± 1.80%, with glycine, proline, and glutamic acid residues in the antler bone peptides (ABPs) contributing most to calcium binding affinity. Infrared spectroscopy confirmed calcium interacted with amino nitrogen atoms and carboxyl oxygen atoms.
In Caco-2 intestinal cell monolayers, ABPs significantly increased calcium transport. In D-galactose-induced aging mice, the ABPs + antler bone calcium group showed higher serum calcium and PINP (bone formation marker), lower phosphorus, ALP, and CTX-1 (bone resorption markers), and significantly higher tibia index and tibia calcium content — demonstrating both increased bone formation and inhibited bone resorption.
Wang, Zhaoguo; Zhai, Xiaorui; Fang, Jiayuan; Wu, Hongyan; Cheng, Yunyun; Gao, Yuan; Chen, Xi; Zheng, Shuo; Liu, Songcai; Hao, Linlin ·
RPEP-06593 · 2022The peptide VL-9 (sequence VGGSDLQAL), derived from the phycoerythrin protein of Acrochaetium sp. red algae, inhibited ACE with an IC50 value of 433.1 ± 1.08 µM.
Molecular docking confirmed that VL-9 acts as a non-competitive inhibitor, binding ACE outside its catalytic site. This is the first report of any bioactive peptide being identified from this particular red alga species.
Windarto, Seto; Lee, Meng-Chou; Nursyam, Happy; Hsu, Jue-Liang ·
RPEP-06595 · 2022Analysis of FDA FAERS data through Q4 2021 revealed:
• 1,827 alopecia cases among 55,994 adverse events reported for CGRP inhibitors (3.26%)
• Class-wide proportional reporting ratio (PRR): 4.06 (95% CI: 3.88-4.25)
• By individual drug: fremanezumab PRR 5.42, erenumab PRR 4.29, galcanezumab PRR 4.11, eptinezumab PRR 2.06
• vs triptans: PRR 12.46 (far more alopecia reports with CGRP inhibitors)
• vs celecoxib: PRR 3.50
• vs anticonvulsants, onabotulinumtoxinA, or beta-blockers: no significant disproportionate signal
• Within the CGRP class: biologic antibodies had PRR 6.11 vs small-molecule CGRP drugs, indicating biologics primarily drive the alopecia signal
Woods, Richard H ·
RPEP-06596 · 2022TSG-6 overexpression in IL-1β-stimulated human nucleus pulposus cells produced multiple beneficial effects: it inhibited inflammatory cytokines (TNF-α, IL-8, IL-6), promoted protective extracellular matrix synthesis (increased collagen II and aggrecan, decreased MMP-3), increased sulfated glycosaminoglycan (sGAG) production, and reduced expression of pain-related molecules including CGRP, Substance P, and nerve growth factor.
All of these effects were mediated through activation of the PI3K/Akt signaling pathway. Both TSG-6 and IL-1β were found to be significantly elevated in degenerated versus normal disc tissue, and IL-1β treatment increased TSG-6 expression in disc cells, suggesting a natural feedback mechanism.
Wu, Bing; Guo, Xiaojin; Yan, Xiujie; Tian, Zikai; Jiang, Wei; He, Xin ·
RPEP-06600 · 2022Adding thymosin alpha 1 (Tα1) to standard tuberculosis chemotherapy improved outcomes in patients who had both pulmonary TB and diabetes. At 6 months, there was no significant difference between groups. But at 12 months, the Tα1 group had significantly higher rates of sputum culture conversion (clearing the TB bacteria), chest lesion absorption, and lung cavity closure compared to chemotherapy alone (all P<0.05).
The Tα1 group also showed improved immune function: higher CD3+, CD4+, CD4+/CD8+ ratios, and NK cell levels compared to baseline and controls. Sputum cytokine levels shifted toward less inflammation — higher IL-2 and IFN-γ (pro-immunity), lower IL-4 and TNF-α (pro-inflammation). Adverse drug reactions did not differ between groups.
Wu, Li; Luo, Pei-Pei; Tian, Yan-Hong; Chen, Lai-Yin; Zhang, Yan-Li · Rct
RPEP-06604 · 2022EA reduced body weight and fat accumulation while restoring gut microbiota after 21 days.
Xia, Xiuwen; Xie, Ya; Gong, Yanju; Zhan, Meng; He, Yan; Liang, Xinyu; Jin, Yue; Yang, Youjun; Ding, Weijun ·
RPEP-06608 · 2022Kisspeptin activates its receptor (KISS1R) to promote GnRH secretion, which in turn controls the entire hypothalamic-pituitary-gonadal axis. Kisspeptin neurons in the arcuate nucleus co-express neurokinin B and dynorphin (forming KNDy neurons) and participate in both positive and negative estrogen feedback to GnRH. In females, kisspeptin regulates follicle development, oocyte maturation, and ovulation. In males, it regulates Leydig cell function, spermatogenesis, sperm function, and reproductive behavior. Mutations in KISS1 or KISS1R genes cause idiopathic hypogonadotropic hypogonadism, central precocious puberty, or female infertility.
Xie, Qinying; Kang, Yafei; Zhang, Chenlu; Xie, Ye; Wang, Chuxiong; Liu, Jiang; Yu, Caiqian; Zhao, Hu; Huang, Donghui ·
RPEP-06609 · 2022In a mouse model of type 2 diabetes (high-fat diet/streptozotocin), 8 weeks of dulaglutide treatment produced multiple cardioprotective effects: it ameliorated insulin resistance, improved glucose tolerance, reduced hyperlipidemia, and promoted fatty acid utilization in the heart muscle.
Critically, dulaglutide attenuated cardiac remodeling and dysfunction by restoring mitochondrial morphology — reversing the mitochondrial fragmentation seen in diabetic hearts. The mechanism was shown to depend on AMPKα2 (AMP-activated protein kinase α2): dulaglutide preserved AMPKα2-dependent mitochondrial homeostasis, and when AMPKα2 was knocked out in mice, dulaglutide's protective cardiac effects were almost completely abolished. These findings were corroborated in neonatal rat heart cells treated with high glucose and palmitic acid.
Xie, Saiyang; Zhang, Min; Shi, Wenke; Xing, Yun; Huang, Yan; Fang, Wen-Xi; Liu, Shi-Qiang; Chen, Meng-Ya; Zhang, Tong; Chen, Si; Zeng, Xiaofeng; Wang, Shasha; Deng, Wei; Tang, Qizhu ·
RPEP-06610 · 2022PCN treatment reduced pain and inflammation in aged rats with hip fractures, reversing substance P signaling.
Xing, Baorui; Feng, Nana; Zhang, Juan; Li, Yunmei; Hou, Xiuxiu; Wu, Hao; Liu, Wendong; Han, Guangpu ·
RPEP-06620 · 2022Melittin — a peptide from bee venom — dramatically improved clinical symptoms of ulcerative colitis in a DSS-induced mouse model, both as a standalone treatment and in combination with sulfasalazine (a standard UC drug). The peptide nearly eliminated histological damage in colon tissue and significantly reduced inflammation. Melittin also showed antioxidant effects by restoring the oxidant/antioxidant balance in damaged tissue. When used alongside sulfasalazine, melittin enhanced the conventional drug's therapeutic effect while attenuating its adverse effects.
Yaghoubi, Atieh; Amel Jamehdar, Saeid; Reza Akbari Eidgahi, Mohammad; Ghazvini, Kiarash ·
RPEP-06621 · 2022The researchers identified TWIST1₁₄₀₋₁₆₂ as an immunogenic peptide sequence within the TWIST1 protein that effectively activated TWIST1-specific CD4+ helper T-cells. Key findings:
- Breast cancer patients showed stronger TWIST1-specific immune responses in short-term culture assays compared to healthy donors, indicating pre-existing immune recognition
- Vaccination with the TWIST1 peptide in humanized mice efficiently expanded TWIST1-reactive helper T-lymphocytes
- TWIST1 is upregulated in tumor cells under hypoxia and promotes metastasis — it appears late in tumor progression when the immune-suppressive microenvironment allows its expression despite its immunogenicity
The study's hypothesis — that highly immunogenic molecules can be expressed by tumors only after establishing immune suppression — provides a rational framework for identifying shared cancer vaccine targets.
Yajima, Yuki; Kosaka, Akemi; Ishibashi, Kei; Yasuda, Shunsuke; Komatsuda, Hiroki; Nagato, Toshihiro; Oikawa, Kensuke; Kitada, Masahiro; Takekawa, Masanori; Kumai, Takumi; Ohara, Kenzo; Ohkuri, Takayuki; Kobayashi, Hiroya ·
RPEP-06625 · 2022Structural studies of the SARS-CoV-2 spike protein HR1HR2 six-helix bundle revealed an extended, well-folded N-terminal region of HR2 that interacts with the HR1 triple helix. Based on this structure:
- An extended HR2 peptide was designed that achieves single-digit nanomolar inhibition in cell-based fusion assays, VSV-SARS-CoV-2 chimera assays, and authentic SARS-CoV-2 infection assays
- No chemical modifications (lipidation, stapling) were needed
- The peptide inhibited all major SARS-CoV-2 variants tested
- ~100-fold more potent than all previously published short, unmodified HR2 peptides
- Very long inhibition lifetime after washout, suggesting it targets a pre-hairpin intermediate state of the spike protein
- The N-terminal extension beyond the HR2 helical region proved critical for potency
Yang, Kailu; Wang, Chuchu; Kreutzberger, Alex J B; Ojha, Ravi; Kuivanen, Suvi; Couoh-Cardel, Sergio; Muratcioglu, Serena; Eisen, Timothy J; White, K Ian; Held, Richard G; Subramanian, Subu; Marcus, Kendra; Pfuetzner, Richard A; Esquivies, Luis; Doyle, Catherine A; Kuriyan, John; Vapalahti, Olli; Balistreri, Giuseppe; Kirchhausen, Tomas; Brunger, Axel T ·
RPEP-06630 · 2022The salmon collagen-derived peptide OGEFG (OG-5) inhibited platelet aggregation by antagonizing P2Y12 receptors, reduced tail thrombosis by 30% in a dose-dependent manner, and significantly reduced atherosclerotic plaque formation in ApoE-/- mice — with effects comparable to aspirin and no side effects. Molecular docking showed strong binding to P2Y12 receptors (-10.70 kcal/mol). OG-5 also inhibited inflammatory cytokine release and vascular smooth muscle cell migration in vitro.
Yang, Yijie; Liu, Hui; Cui, Liyuan; Liu, Yibo; Fu, Lulu; Li, Bo ·
RPEP-06632 · 2022Conjugating the cell-penetrating TAT peptide to a frog-derived trypsin inhibitor (kunitzin-OV2) produced dramatic improvements: 32-fold increased antibacterial activity against E. coli and new antiproliferative activity against cancer cells that the original peptide lacked. A phenylalanine-substituted variant (TAT-F9-KOV2) showed 20-25 fold greater antiproliferative activity against lung cancer cells and was also active against breast cancer and glioblastoma lines. The CPP conjugation solved the cell penetration barrier without increasing membrane lysis.
Yao, Junting; Yin, Weining; Chen, Yuqing; Chen, Xiaoling; Jiang, Yangyang; Wang, Tao; Ma, Chengbang; Zhou, Mei; Chen, Tianbao; Shaw, Chris; Wang, Lei ·
RPEP-06633 · 2022The vaccine group achieved a 5-year esophageal cancer-specific survival (ECSS) of 60.0% compared to 32.4% in the control group (P = 0.045). While relapse-free survival did not reach statistical significance (5-year RFS: 45.3% vs 32.5%), the recurrence rate significantly decreased with the number of peptide antigens that successfully induced antigen-specific cytotoxic T lymphocytes, suggesting a dose-response relationship in immune activation.
The survival benefit was most pronounced in patients whose tumors were CD8+ and PD-L1 double negative: vaccinated patients in this subgroup achieved 68.0% 5-year ECSS versus only 17.7% in controls (P = 0.010). This suggests the tumor immune microenvironment strongly influences peptide vaccine effectiveness.
Yasuda, Takushi; Nishiki, Kohei; Hiraki, Yoko; Kato, Hiroaki; Iwama, Mitsuru; Shiraishi, Osamu; Yasuda, Atsushi; Shinkai, Masayuki; Kimura, Yutaka; Sukegawa, Yasushi; Chiba, Yasutaka; Imano, Motohiro; Takeda, Kazuyoshi; Satou, Takao; Shiozaki, Hitoshi; Nakamura, Yusuke ·
RPEP-06637 · 2022Multiple cardiovascular outcome trials have demonstrated that GLP-1 receptor agonists provide renal protective effects in patients with type 2 diabetes beyond their glucose-lowering action. The kidney benefits come through two pathways:
- Direct effects on the kidney: inhibition of oxidative stress and inflammation, and induction of natriuresis (increased sodium excretion in urine)
- Indirect effects: reduction of conventional DKD risk factors including blood glucose, blood pressure, and body weight
Early evidence from dual and triple receptor combination agents (targeting GIP, glucagon, and GLP-1 receptors simultaneously) suggests even greater potential for this drug class in treating DKD.
Yu, Ji Hee; Park, So Young; Lee, Da Young; Kim, Nan Hee; Seo, Ji A ·
RPEP-06641 · 2022Optimized hydrolysis of kenaf seed protein (65°C, pH 6.5, 2.25 hours, E/S ratio 0.03) achieved 55.28% degree of hydrolysis and 75.51% ACE inhibitory activity. The <2 kDa and 2-5 kDa peptide fractions showed the highest activity (82.27% and 83.69% respectively).
Six novel ACE-inhibitory peptides were identified from the 2-5 kDa fraction by QTOF LC-MS: LYWSYLYN, ALFYWVS, LLLHAL, AKSCVVFP, INPPSTTN, and WTIPTPS. Kinetic studies revealed LYWSYLYN had the highest Michaelis constant (Km) and maximum velocity (Vmax) values with the lowest inhibitor constant (Ki), confirming it as the most potent ACE inhibitor among the six peptides.
Zaharuddin, Nurul Dhania; Barkia, Ines; Wan Ibadullah, Wan Zunairah; Zarei, Mohammad; Saari, Nazamid ·
RPEP-06643 · 2022The analgesic effect of SCS increased with stimulation intensity between 20% and 80% motor thresholds. All tested frequencies (2, 15, 50, 100, 10,000 Hz, and alternating 2/100 Hz) were similarly effective at reducing pain.
Critically, different frequencies operated through distinct opioid peptide mechanisms: 2 Hz SCS significantly increased methionine enkephalin in cerebrospinal fluid and its effect was blocked by mu or kappa opioid receptor antagonists. 100 Hz SCS was blocked only by a kappa antagonist. 10 kHz SCS was blocked by antagonists at any of the three opioid receptor types (mu, delta, or kappa). No tolerance developed within 24 hours of continuous stimulation.
Zhai, Fu-Jun; Han, Song-Ping; Song, Tian-Jia; Huo, Ran; Lan, Xing-Yu; Zhang, Rong; Han, Ji-Sheng ·
RPEP-06645 · 2022Thymosin beta-4 (Tβ4) eye drops at both 0.05% and 0.1% concentrations improved all clinical measures of dry eye disease in mice within 7 days. The peptide increased tear production, reduced corneal staining (a measure of surface damage), restored goblet cells in the conjunctiva (which produce the protective mucus layer), and reduced cell death in the cornea and conjunctiva.
The mechanism was anti-inflammatory: Tβ4 reduced inflammatory cytokine levels and CD4+ T cell infiltration by blocking NF-κB activation — the master inflammatory switch. Both doses were effective.
Zhai, Yanfang; Zheng, Xiaoxiang; Mao, Yunyun; Li, Kai; Liu, Yanhong; Gao, Yuemei; Zhao, Mengsu; Yang, Rui; Yu, Rui; Chen, Wei · Animal Study (Mouse Model)
RPEP-06646 · 2022Silencing TRPV1+ nociceptors (pain-sensing neurons) in the gut through three different methods — chemogenetic silencing, adenoviral colon-specific silencing, and pharmacological ablation — all resulted in more severe intestinal inflammation and impaired tissue repair in mouse models.
The disruption of nociception caused significant alterations in gut microbiota composition, producing a transmissible dysbiosis (meaning the disrupted microbiome could transfer disease susceptibility). Mono-colonization of germ-free mice with Gram-positive Clostridium species promoted tissue protection through a nociceptor-dependent pathway. Mechanistically, silencing nociceptors decreased levels of substance P, and therapeutic delivery of substance P restored tissue-protective effects in a microbiota-dependent manner. Analysis of intestinal biopsies from IBD patients showed dysregulated nociceptor gene expression, suggesting clinical relevance.
Zhang, Wen; Lyu, Mengze; Bessman, Nicholas J; Xie, Zili; Arifuzzaman, Mohammad; Yano, Hiroshi; Parkhurst, Christopher N; Chu, Coco; Zhou, Lei; Putzel, Gregory G; Li, Ting-Ting; Jin, Wen-Bing; Zhou, Jordan; Hu, Hongzhen; Tsou, Amy M; Guo, Chun-Jun; Artis, David ·
RPEP-06648 · 2022A DNA nanodevice carrying peptide neoantigens achieved remarkable results in mouse cancer models. In the B16-OVA melanoma model, it inhibited tumor growth by 50%. Even more impressively, when loaded with tumor-specific neoantigens for MC-38 colorectal cancer, it induced complete tumor regression in 80% of mice.
The key innovation is a sulfonium-based bio-orthogonal chemistry that enables reversible attachment and controlled release of antigen peptides from the DNA scaffold. The nanodevice was effectively internalized by antigen-presenting cells, enhanced cytokine secretion (TNF-α, IL-6, IL-12), stimulated antigen-specific CD8+ killer T cells, and significantly prevented lung metastases of melanoma when combined with CpG adjuvant.
Zhang, Yaping; Xu, Hongkun; Jiang, Leying; Liu, Zhaodi; Lian, Chenshan; Ding, Xiaofeng; Wan, Chuan; Liu, Na; Wang, Yuena; Yu, Zhiqiang; Zhu, Lizhi; Yin, Feng; Li, Zigang · Animal And Cell
RPEP-06649 · 2022The Smac-TLR7/8 peptide hydrogel self-assembled into nanofibers with porous structure and excellent biocompatibility. Upon gamma-ray radiation, it effectively polarized macrophages from the tumor-promoting M2 phenotype to the antitumor M1 phenotype.
Combined with radiotherapy, the hydrogel increased tumor necrosis factor secretion, activated antitumor immune responses, and effectively inhibited tumor growth. The macrophage repolarization also rebuilt the immunosuppressive tumor microenvironment and created immunogenic phenotypes in solid tumors.
This enhanced PD-1 blockade efficacy by increasing tumor-infiltrating lymphocytes (TILs) and decreasing regulatory T cells (Treg) in two different immune activity tumor mouse models, demonstrating synergy between the hydrogel, radiotherapy, and immunotherapy.
Zhang, Yumin; Feng, Zujian; Liu, Jinjian; Li, Hui; Su, Qi; Zhang, Jiamin; Huang, Pingsheng; Wang, Weiwei; Liu, Jianfeng ·
RPEP-06650 · 2022Cryo-EM structures revealed how tirzepatide (dual GIP/GLP-1 agonist) and peptide 20 (triple GIP/GLP-1/glucagon agonist) achieve their multiplexed receptor activation. The structures showed both common and unique binding features at near-atomic resolution, explaining how a single peptide can effectively activate two or three different receptors. Key finding: retention of glucagon receptor function is required for the triple agonist to achieve advantages over GLP-1 monotherapy alone.
Zhao, Fenghui; Zhou, Qingtong; Cong, Zhaotong; Hang, Kaini; Zou, Xinyu; Zhang, Chao; Chen, Yan; Dai, Antao; Liang, Anyi; Ming, Qianqian; Wang, Mu; Chen, Li-Nan; Xu, Peiyu; Chang, Rulve; Feng, Wenbo; Xia, Tian; Zhang, Yan; Wu, Beili; Yang, Dehua; Zhao, Lihua; Xu, H Eric; Wang, Ming-Wei ·
RPEP-06653 · 2022Researchers designed two short peptides from the spider venom toxin GsMTx4. The Type I peptide (Pept 01, 17 residues) showed comparable inhibitory efficacy against the stretch-activated big potassium channel (SAKcaC) as the full-length GsMTx4. Remarkably, the Type II peptide (Pept 02, just 10 residues) was even more potent than the parent toxin.
Both peptides lost their inhibitory effect when tested against a mechano-insensitive channel variant (STREX-del) and a non-mechanosensitive potassium channel (mouse Slo1), confirming they work specifically by modifying the mechanogate — the part of the channel that responds to physical stretching. Molecular dynamics simulations revealed both peptides share a structural motif: a hydrophobic head followed by a positively charged protrusion that likely mediates channel-lipid interactions.
Zhou, Nan; Li, Hui; Xu, Jie; Shen, Zhong-Shan; Tang, Mingxi; Wang, Xiao-Hui; Su, Wan-Xin; Sokabe, Masahiro; Zhang, Zhe; Tang, Qiong-Yao ·
RPEP-06667 · 2023Two peptides derived from the ACE2 receptor's α1-helix effectively blocked SARS-CoV-2 spike protein binding. The shorter peptide [30-42] (13 amino acids) achieved maximal inhibition at lower concentrations than the longer peptide [22-44] (23 amino acids), demonstrating that shorter, well-designed peptides can be more potent viral blockers.
Molecular docking models confirmed the experimental findings and identified critical amino acid residues responsible for the inhibitory effect. Both peptides blocked the spike protein's receptor-binding domain residues known to interact with ACE2.
Abouhajar, Fatimah; Chaudhuri, Rohit; Valiulis, Santino N; Stuart, Daniel D; Malinick, Alexander S; Xue, Min; Cheng, Quan · Laboratory
RPEP-06670 · 2023Using an in vitro MHC-I antigen presentation assay with the SIINFEKL peptide (H-2 Kb-restricted OVA epitope), the study found:
- Spacer type had the largest impact on neoantigen processing and MHC-I presentation efficiency
- Alanine-based linkers promoted more efficient peptide presentation than the commonly used GGGS linker
- Peptide position within the concatenated chain had minimal impact on presentation
- Flanking regions had minimal impact on presentation
These findings suggest that spacer selection — often treated as an afterthought in vaccine design — is actually a critical determinant of vaccine immunogenicity.
Aguilar-Gurrieri, Carmen; Barajas, Ana; Rovirosa, Carla; Ortiz, Raquel; Urrea, Victor; de la Iglesia, Nuria; Clotet, Bonaventura; Blanco, Julià; Carrillo, Jorge ·
RPEP-06679 · 2023Across 12 randomized controlled trials involving 445 participants, GLP-1 analogs consistently demonstrated effects on multiple appetite-related parameters:
- **Appetite suppression**: Most studies showed reduced hunger and increased fullness
- **Delayed gastric emptying**: Food stayed in the stomach longer, prolonging satiety
- **Food preference changes**: Shifts away from high-fat and high-calorie foods
- **Taste alterations**: Changes in taste sensitivity and perception
The review found that GLP-1 drugs work through these multiple, complementary mechanisms rather than a single pathway — helping explain their superior weight loss efficacy compared to earlier anti-obesity medications that typically targeted only one mechanism.
Aldawsari, Malikah; Almadani, Fatima A; Almuhammadi, Nujud; Algabsani, Sarah; Alamro, Yara; Aldhwayan, Madhawi ·
RPEP-06681 · 2023All four anti-CGRP monoclonal antibodies (eptinezumab, erenumab, fremanezumab, and galcanezumab) are superior to placebo for reducing monthly migraine days in both episodic and chronic migraine patients. The pooled analysis of randomized controlled trials showed consistent efficacy across all four treatments, with no major differences between them.
The evidence was assessed using the rigorous GRADE methodology and compiled into standardized evidence tables. These tables evaluate both the efficacy (reduction in migraine days) and safety profile of each antibody, providing a comprehensive evidence base for clinical guideline development.
Aleksovska, Katina; Hershey, Andrew D; Deen, Marie; Icco, Robert de; Lee, Mi Ji; Diener, Hans-Christoph ·
RPEP-06683 · 2023L. lactis NZ9000 engineered with signal peptide SPK1 secreted KRAS oncopeptides (mutant 68V-DT and wild-type KRAS) more efficiently than the mutant signal peptide SPKM19, producing approximately 1.3-fold higher yields. This was unexpected, as SPKM19 had previously outperformed SPK1 with a different reporter protein.
In BALB/c mice, oral immunization with SPK1-mediated KRAS secretion produced a superior IgA immune response compared to SPKM19. However, even the SPKM19 construct triggered a positive IgA response in intestinal washes. The discrepancy between signal peptide performance with different cargo proteins was attributed to differences in size and secondary conformation of the mature proteins.
Alias, Nur Aqlili Riana; Hoo, Winfrey Pui Yee; Siak, Pui Yan; Othman, Siti Sarah; Mohammed Alitheen, Noorjahan Banu; In, Lionel Lian Aun; Abdul Rahim, Raha; Song, Adelene Ai-Lian ·
RPEP-06685 · 2023Of 158 patients, 44% achieved a 50% or greater reduction in headache days at month 6. In this responder group, headache days decreased by 9.4 days/month (p<0.001). Beyond headache reduction, the ratio of days with specific symptoms decreased significantly:
- Photophobia: -19.5% (p<0.001)
- Phonophobia: -12.1% (p=0.010)
- Aura: -25.1% (p=0.008)
These reductions exceeded the proportional decrease in headache days, meaning the symptoms improved independently, not just because there were fewer migraines. Nausea and dizziness decreased only in proportion to fewer headache days. Higher baseline photophobia ratios predicted better response between months 3-6 (IRR=0.928, p=0.040), suggesting CGRP's role in light sensitivity may identify patients likely to benefit.
Alpuente, Alicia; Torre-Sune, Anna; Caronna, Edoardo; Gine-Cipres, Eulalia; Torres-Ferrús, Marta; Pozo-Rosich, Patricia ·
RPEP-06686 · 2023Six peptides based on bacterial membrane-targeting sequences (MTSs) all showed cell-penetrating ability. Two D-peptide versions — d-EcMTS (from E. coli) and d-TpMTS (from T. pallidum) — demonstrated the additional critical ability to escape from endosomes after cellular uptake and localize at the endoplasmic reticulum (ER).
The utility was validated by successful intracellular delivery of green fluorescent protein (GFP), a large biomacromolecule that cannot enter cells on its own. The D-amino acid configuration provides protease resistance, addressing the stability limitation of natural L-peptide CPPs. The results suggest that the vast pool of bacterial MTSs represents an untapped resource for developing novel endosome-escaping cell-penetrating peptides.
An, Chuanjing; Wei, Sheng; Dao, Yuankun; Wang, Xiaoya; Dong, Weidong; You, Xue; Tian, Chao; Zhang, Zhili; Dong, Suwei ·
RPEP-06688 · 2023High-throughput screening and in silico design identified novel small molecule allosteric enhancers of GC-A. These compounds enhanced ANP and BNP effects in cellular systems expressing GC-A and enhanced ANP-induced vasorelaxation in rat aortic rings. The mechanism is novel — not mediated through previously known allosteric binding sites. Selectivity between GC-A and the related receptor GC-B depended on a single amino acid residue. The compounds represent a new class of tools for enhancing natriuretic peptide signaling.
Andresen, Henriette; Pérez-Ternero, Cristina; Robinson, Jerid; Dickey, Deborah M; Hobbs, Adrian J; Potter, Lincoln R; Levy, Finn Olav; Cataliotti, Alessandro; Moltzau, Lise Román ·
RPEP-06689 · 2023Using fluorescence lifetime imaging microscopy (FLIM) with phasor analysis, researchers visualized TP10's behavior on cancer cell-derived membrane vesicles in real time. They identified concentration-dependent mechanisms: at lower concentrations, TP10 translocated across membranes and accumulated in the vesicle lumen (internalization). At higher concentrations, it induced membrane perturbation, pore formation, and ultimately membrane collapse and disruption. The FLIM-phasor approach enabled monitoring of these spatially heterogeneous, highly dynamic events as they occurred.
Anselmo, Sara; Sancataldo, Giuseppe; Baiamonte, Concetta; Pizzolanti, Giuseppe; Vetri, Valeria ·
RPEP-06690 · 2023Among 196,691 type 1 diabetes patients, 1,822 were treated with GLP-1 RAs and 992 with SGLT2 inhibitors for at least 6 months. Both lowered HbA1c: SGLT2i reduced it by 2.6 mmol/mol (0.2%) and GLP-1 RA by 5.4 mmol/mol (0.5%).
Over 5 years, SGLT2i users showed kidney function preservation (eGFR +3.5 ml/min/1.73m²) while GLP-1 RA users showed decline (eGFR -7.2 ml/min/1.73m²). SGLT2i users had significantly lower risks of heart failure (RR 0.44, p=0.009), chronic kidney disease (RR 0.49, p=0.012), and all-cause hospitalization (RR 0.59, p<0.0001). However, SGLT2i users had higher rates of diabetic ketoacidosis (RR 2.08, p=0.031) and urinary tract infections (RR 2.27, p=0.019).
Anson, Matthew; Zhao, Sizheng S; Austin, Philip; Ibarburu, Gema H; Malik, Rayaz A; Alam, Uazman ·
RPEP-06693 · 2023Cathelicidin levels differed significantly across all three groups (P<0.050):
- Leprosy patients: 256.8 ± 22.9 pg/ml
- Household contacts: 25.9 ± 2.7 pg/ml
- Healthy controls: 1.4 ± 0.1 pg/ml
The approximately 10-fold difference between patients and contacts, and the nearly 200-fold difference between patients and healthy controls, demonstrates a dose-response relationship between cathelicidin production and the degree of exposure to or infection with Mycobacterium leprae. Notably, even asymptomatic household contacts had significantly elevated cathelicidin compared to unexposed healthy individuals.
Argentina, Fifa; Suwarsa, Oki; Gunawan, Hendra; Berbudi, Afiat ·
RPEP-06694 · 2023HBD-3 gene expression in leprosy skin lesions had a median value of 260.61 compared to 1.00 in healthy skin (p < 0.0001) — a roughly 260-fold increase. Cathelicidin expression in lesions was 38.72 versus 1.00 in healthy skin (p < 0.0001).
Critically, household contacts who did not have leprosy also showed elevated antimicrobial peptide levels: HBD-3 at 7.93 and cathelicidin at 9.8, both substantially higher than healthy individuals. Normal (non-lesional) skin in leprosy patients showed intermediate levels (HBD-3: 1.91; cathelicidin: 0.48). These findings suggest a gradient of antimicrobial peptide response from healthy individuals through exposed contacts to active disease, potentially reflecting both infection response and protective immunity.
Argentina, Fifa; Suwarsa, Oki; Gunawan, Hendra; Berbudi, Afiat ·
RPEP-06695 · 2023Out of 43,710 total comments, 620 mentioned insomnia, 353 anxiety, and 204 depression related to GLP-1 RAs.
Arillotta, Davide; Floresta, Giuseppe; Guirguis, Amira; Corkery, John Martin; Catalani, Valeria; Martinotti, Giovanni; Sensi, Stefano L; Schifano, Fabrizio ·
RPEP-06698 · 2023Across 16 Phase IIIa trials (n=11,159; subcutaneous semaglutide n=3,150; oral semaglutide n=4,116):
- GI disorders: 41.9% (subcutaneous) / 39.1% (oral) vs 22.0% / 24.8% comparators — most common during dose escalation, decreasing with continued therapy
- No increased risk vs comparators for: kidney disorders, acute pancreatitis, malignant neoplasms, hypoglycemia, heart failure, or other cardiovascular events
- Cholelithiasis (gallstones): incidence higher with both formulations vs placebo
- Diabetic retinopathy: higher with subcutaneous semaglutide vs placebo in SUSTAIN 6
- Small pulse rate increases with both formulations; no increased arrhythmias
- Fatal adverse events: similar rates between semaglutide and comparators
- CVOTs: reduced MACE with subcutaneous semaglutide; non-inferiority met with oral
Aroda, Vanita R; Erhan, Umut; Jelnes, Peter; Meier, Juris J; Abildlund, Morten Tind; Pratley, Richard; Vilsbøll, Tina; Husain, Mansoor ·
RPEP-06700 · 2023Bioinformatics analysis of all reviewed piscidin sequences in the UniProt database revealed that these fish-exclusive antimicrobial peptides share amphipathic alpha-helical structures with positively charged residues that drive their antibacterial activity. Piscidins are effective against both Gram-positive and Gram-negative bacteria that cause disease in fish and humans.
A key advantage is their stability in high-salt and metal-rich environments — conditions that disable many other antimicrobial peptides. The study identified potential applications beyond antibiotics, including anti-cancer and anti-inflammatory uses, and suggests piscidins could inspire treatments for multidrug-resistant bacterial infections.
Asensio-Calavia, Patricia; González-Acosta, Sergio; Otazo-Pérez, Andrea; López, Manuel R; Morales-delaNuez, Antonio; Pérez de la Lastra, José Manuel ·
RPEP-06702 · 2023Of 37 patients with metastatic Merkel cell carcinoma who received 1-5 cycles of PRRT using 177Lu- or 90Y-labeled somatostatin analogs (cumulative activity 1.5-30 GBq), radiographic response data was available for 19 who received PRRT alone. Six of these 19 patients (31.6%) achieved objective responses ranging from partial to complete. No severe adverse events were reported across the treated cohort.
Askari, Emran; Moghadam, Soroush Zarehparvar; Wild, Damian; Delpassand, Ebrahim; Baldari, Sergio; Nilica, Bernhard; Hartrampf, Philipp E; Kong, Grace; Grana, Chiara Maria; Alexander Walter, Martin; Capoccetti, Francesca; Kasi, Pashtoon Murtaza; Strosberg, Jonathan ·
RPEP-06703 · 2023Combining the milk-derived antimicrobial peptide lactoferricin (Lfcin) with an enzyme that disrupts bacterial communication (His6-OPH, a quorum quenching enzyme) produced synergistic antimicrobial effects against bacteria and yeasts. The enzyme-peptide combination killed microorganisms more effectively than the peptide alone. Additionally, Lfcin stabilized the enzyme's activity and increased its catalytic efficiency for breaking down bacterial signaling molecules (quorum sensing lactones).
Molecular docking simulations first predicted which peptide-enzyme pairings would work best, and experimental testing confirmed that His6-OPH/Lfcin was the optimal combination among three lactoferrin-derived peptides and two enzymes tested.
Aslanli, Aysel; Domnin, Maksim; Stepanov, Nikolay; Efremenko, Elena · Basic Research
RPEP-06704 · 2023CPP-based drug delivery systems effectively inhibited tumor volume and weight in mouse models across numerous studies. However, the review found that only rare cases demonstrated actual tumor level reduction beyond volume shrinkage, and even fewer progressed to further development stages.
The integration of chemical synthesis with CPP development has been the most successful approach, with at least one CPP-based system reaching clinical trials as a diagnostic imaging tool. The field has expanded from the original two classes (cationic and amphipathic) to include hydrophobic and cyclic CPPs, each with different strengths for drug delivery.
Asrorov, Akmal M; Wang, Huiyuan; Zhang, Meng; Wang, Yonghui; He, Yang; Sharipov, Mirkomil; Yili, Abulimiti; Huang, Yongzhuo ·
RPEP-06707 · 2023In 33 COVID-19 patients and 11 healthy controls analyzed by scRNA-seq and TCR-seq:
- CD3+ KLRD1+ NKT cells increased with Tα1 in COVID-19 (p = 0.024) and healthy controls (p = 0.016)
- TBX21+ CD8+ NKT cells increased with Tα1 in COVID-19 (p = 0.010) and healthy controls (p = 0.031)
- Tα1-treated NKT cells showed higher expression of KLRB1, PRF1 (perforin) and enrichment of NK cell cytotoxicity, chemokine signaling, and JAK-STAT pathways
- Increased TRBV9-TRBJ1-1 T cell receptor pair in both groups after Tα1 treatment
- 1,389 common CDR3 sequences between untreated COVID-19 and healthy, but 0 common sequences between treated groups — indicating Tα1 diversifies T cell clones
- Tα1 promotes NKT cell activation and cytotoxicity through gene expression regulation
Bai, Han; Liang, Liyuan; Qi, Xin; Xu, Yao; Liu, Yijia; Ren, Doudou; Cai, Zeqiong; Mao, Weikang; Wang, Xiaorui; Qin, Hongyu; Hu, Fang; Shi, Bingyin ·
RPEP-06710 · 2023Bread enriched with 60% cellular chickpea powder (CCP) significantly increased postprandial GLP-1 and PYY responses compared to standard white bread (time × treatment, P = 0.001 for both hormones). The GLP-1 incremental area under the curve (iAUC) showed a mean difference of 3,101 pM/min (95% CI: 1,891–4,310; P-adjusted < 0.001) between the 60% and 0% CCP breads.
The 60% CCP bread also produced approximately 40% lower glucose iAUC (P-adjusted < 0.001) compared to regular white bread. In vitro studies confirmed that intact chickpea cells digest slowly, explaining the sustained hormone release and improved glycemic response.
Bajka, Balazs H; Pinto, Ana M; Perez-Moral, Natalia; Saha, Shikha; Ryden, Peter; Ahn-Jarvis, Jennifer; van der Schoot, Alice; Bland, Catherine; Berry, Sarah E; Ellis, Peter R; Edwards, Cathrina H ·
RPEP-06711 · 2023The review identifies peptide-based hydrogels as leading biomaterials due to three key properties: tunable mechanical stability, high water content, and high biocompatibility. Key design parameters include pH sensitivity, amino acid composition within the peptide sequence, and cross-linking techniques. These hydrogels effectively mimic extracellular matrix proteins, providing the three-dimensional environment cells need to grow into functional tissue. Multiple types of peptide-based materials and their self-assembly mechanisms are discussed.
Bakhtiary, Negar; Ghalandari, Behafarid; Ghorbani, Farnaz; Varma, Swastina Nath; Liu, Chaozong ·
RPEP-06717 · 2023GLP-1 receptor agonists reduced adverse cerebrovascular outcomes by 17% (RR 0.83, 95% CI 0.76–0.91, I²=0%) across 28 RCTs with 74,148 patients. Specifically, ischemic stroke was reduced by 27% (RR 0.73, 95% CI 0.60–0.89) and the composite of ischemic stroke/TIA by 24% (RR 0.76, 95% CI 0.65–0.90). Nonfatal stroke was reduced by 15% (RR 0.85, 95% CI 0.76–0.94), but reductions in fatal stroke (RR 0.80) and hemorrhagic stroke (RR 0.92) were not statistically significant.
Benefits were statistically significant for dulaglutide and both subcutaneous and oral semaglutide. Patients with shorter diabetes duration and higher baseline kidney function (eGFR) showed greater benefit.
Banerjee, Mainak; Pal, Rimesh; Mukhopadhyay, Satinath; Nair, Kirthana ·