Research Hub
The living record of
peptide science.
PubMed studies synced daily. Active clinical trials. Evidence updates when the science materially changes. Monthly synthesis for practitioners.
Layer 1
Study feed
Gli1⁺ cell aggregates promote type H vessel formation and orchestrate bone defect regeneration.
Stem Cell Res Ther
Chao Ma, Yu-Ru Gao, Hao Wang +14 more
Rapid and stable regeneration of bone defects remains a pressing clinical challenge. We previously fabricated stem cell aggregates (CA) by mimicking developmental condensation and demonstrated their efficacy in promoting bone defect repair. Endogenous Gli1+ skeletal stromal/progenitor cells (SSPCs) are a pivotal SSPC subtype known to maintain bone homeostasis and enhance bone regeneration; however, the functional properties and translational potential of CA derived from these cells (Gli1+ CA) remain largely elusive.
Salivary innate immune peptides are associated with dental caries experience in young adults.
Clin Oral Investig
Carla P Lozano, Constanza Echeverría, Natalia García-Manríquez +2 more
Saliva has traditionally been studied in relation to dental caries through parameters such as flow rate, pH, and buffering capacity. However, additional components, particularly proteins of the innate immune system, may also contribute to caries development or prevention. This study evaluated whether antimicrobial peptides (AMPs) in saliva are associated with caries status in young adults.
Current trends in semaglutide therapy and strategies to improve its bioavailability.
Expert Opin Drug Deliv
Swasthik Nayak, Akanksha D Dessai, Usha Y Nayak
A GLP-1 Receptor Agonist, semaglutide, is given in the management of type 2 diabetes mellitus and obese individuals. However, oral semaglutide exerts very low bioavailability due to multiple gastrointestinal and biopharmaceutical barriers. Delivery of oral semaglutide becomes difficult due to instability in GI fluids, degradation through proteolysis by various enzymes, and mucus diffusion limitation; epithelial permeability restricts the oral absorption of the drug, due to which the oral bioavailability of semaglutide is exceedingly low. This review identifies methods that enhance oral bioavailability as well as treatment efficacy of semaglutide.
Elevated B-type natriuretic peptide levels as prognostic biomarkers for walking independence in patients with stroke in the post-acute phase.
Heart Vessels
Genki Kai, Takumi Noda, Kensuke Ueno +6 more
B-type natriuretic peptide (BNP) is recognized as a useful prognostic biomarker not only in patients with heart failure (HF) but also in those with stroke. However, the relationship between BNP levels in the post-acute stroke phase and walking independence, an important outcome for patients with stroke, remains unclear. This study investigated the association between BNP levels and walking independence in patients during the post-acute stroke phase. This retrospective study included 650 consecutive patients with stroke (median age: 77 years; male: 53.2%) in the post-acute phase. BNP or N-terminal prohormone of BNP (NT-proBNP) levels were measured at admission to the post-acute rehabilitation ward. To investigate the association between BNP levels and walking independence, the patients were divided into two groups: high BNP (BNP ≥ 200 pg/ml or NT-proBNP ≥ 900 pg/ml) and low BNP. Of 650 patients, 329 (50.6%) achieved walking independence during hospitalization. After adjusting for confounding factors, higher BNP levels were significantly associated with lower walking independence (hazard ratio [HR]: 0.54; 95% confidence interval [CI]: 0.36-0.82; p = 0.004). This association remained consistent across subgroups. The group without an HF diagnosis but with high BNP levels was also associated with reduced walking independence compared to the group without an HF diagnosis but with low BNP levels (HR: 0.42; 95% CI 0.25-0.70; p < 0.001). Elevated BNP levels were associated with lower walking independence in patients with stroke during the post-acute phase. BNP levels in the post-acute phase may be a useful marker for risk stratification in stroke recovery.
Food-Derived Elastin Peptides Improve Glucose Metabolism and Protect Renal Vasculature in Stroke-Prone Spontaneously Hypertensive Rats Despite Modest Dipeptidyl Peptidase 4 Inhibition.
Nutrients
Kumiko Takemori, Yuki Nakamura, Kenji Sato +3 more
Elastin-derived peptides (EPs) from food sources may be multifunctional dietary components that support metabolic and vascular health. However, their in vivo physiological actions remain incompletely understood. This study investigated the effects of bonito bulbus arteriosus-derived EPs on glucose metabolism, GLP-1 elevation associated with enhanced early-phase insulin secretion, and renal vascular integrity in stroke-prone spontaneously hypertensive rats (SHRSP) with glucose intolerance.
Acute pretrauma ethanol exacerbates PTSD-like phenotype in rats and is reversed by early intranasal ketamine.
Sci Rep
Bar Eilat Yogev, Gal Levi, Noa Efroni +4 more
Alcohol consumption before trauma is a prevalent but understudied risk factor for posttraumatic stress disorder (PTSD). This study investigated whether acute ethanol exposure prior to trauma modulates PTSD-like symptom development in rats, identified hippocampal mechanisms involved, and tested an early post-trauma intervention. Adult male Sprague-Dawley rats received ethanol (1.6 g/kg, 40% v/v, intraperitoneal) or saline 4 h or 30 min before predator scent stress (PSS) or sham-PSS exposure. Seven days post-exposure, anxiety-like behavior (elevated plus-maze), acoustic startle response, and cue-induced freezing were assessed using validated cut-off behavioral criteria to classify PTSD-like phenotypes. Hippocampal CA1 dendritic morphology was examined in relation to behavioral outcomes. In parallel cohorts, immunofluorescence quantified hippocampal hyperpolarization-activated cyclic nucleotide-gated channel 1 (HCN1), neuropeptide Y (NPY), NPY-Y1 receptor (NPY-Y1-R), and brain-derived neurotrophic factor (BDNF) 1 h post-PSS. A separate ethanol-pretreated group received subanesthetic intranasal ketamine (0.6 mg/kg) via amylolipid nanovesicles (ketamine-ALN) 1 h after PSS. Rats administered ethanol 4 h-but not 30 min-before PSS showed a higher prevalence of PTSD-like phenotypes at 7 days and significantly greater CA1 dendritic retraction. Combined ethanol and PSS exposure was associated with reduced BDNF and NPY levels, increased HCN1, and loss of NPY-Y1-R immunoreactivity, consistent with a hypoexcitable, plasticity-resistant state in the hippocampus. Rats that received early post-PSS ketamine-ALN showed lower cue-induced freezing, a more resilient behavioral profile, and less dendritic atrophy than unloaded-ALN-treated rats. Pre-trauma timed ethanol exposure was associated with a hippocampal "double-hit" involving HCN1 and NPY-Y1-R circuits, together with greater PTSD-like vulnerability. A single early post-trauma intranasal subanesthetic dose of ketamine was associated with a lower prevalence of PTSD-like phenotype, suggesting a promising preventive strategy for alcohol-exposed trauma survivors.
Genistein alleviates skin inflammation in atopic dermatitis by inhibiting mast cell degranulation through toll-like receptor.
Phytomedicine
Hongfen Du, Na Wang, Chao Wang +8 more
Atopic dermatitis (AD) is a mast cell-driven inflammatory disorder with limited treatment options. This study aimed to explore the therapeutic potential and mechanism of the natural compound genistein against AD.
Exploring the anti-gout mechanism of Erding granules based on network pharmacology and experimental verification.
Pak J Pharm Sci
Guanglei Wang, Liang He, Yihua Zhang +1 more
Gout is a common form of inflammatory arthritis.
MYCN drives pediatric glioma transformation from neural progenitors and creates distinct therapeutic vulnerabilities.
Cell Rep
Taylor A Gatesman, Srinidhi Varadharajan, Brenden J Johnson +36 more
MYCN functions as a developmental oncogene, but its role in pediatric high-grade gliomas (pHGGs) remains unclear. In co-operation with Trp53 and Pten loss, MYCN initiates tumorigenesis and establishes an origin for MYCN-driven pHGGs. This transformation creates a vulnerability to PI3K and mTOR inhibition. However, prolonged treatment drives adaptive resistance through MYCN protein rebound, mediated by the attenuation of IGFBP5 and the induction of insulin-like growth factor 2. Although insulin pathway feedback has been implicated in resistance to PI3K targeted therapies, MYCN emerges as the central node of this adaptive program. Resistance can be overcame by sustained MYCN suppression using PI3K and mTOR inhibitors, combined with insulin-like growth factor 1 receptor and insulin receptor inhibitors or dietary intervention. A degradation-resistant MYCN isoform abolishes this response, establishing MYCN as both an initiating oncogene and a resistance driver and revealing a mechanistically defined therapeutic vulnerability.
Post hoc analysis of SURMOUNT-J: tirzepatide versus placebo and predicted 10-year cardiovascular disease risk in Japanese adults with obesity disease.
Curr Med Res Opin
Koichi Node, Rachel L Batterham, Hong Liu-Seifert +5 more
Obesity management is central to reducing cardiovascular disease (CVD) risk. In the phase 3 SURMOUNT-J trial, tirzepatide significantly reduced body weight and improved cardiometabolic parameters versus placebo in Japanese adults with obesity disease (as defined by the Japan Society for the Study of Obesity [JASSO], referring to obesity requiring clinical treatment) and without diabetes. We conducted post hoc analyses to predict 10-year CVD risk and the number of potentially preventable CVD events based on predicted risk with tirzepatide versus placebo.
Comparative Pharmacokinetics of Gentamicin in Healthy Young-Adult and Geriatric Horses.
J Vet Pharmacol Ther
Michelle L Ceresia, Daniela Bedenice, Andrew Gestrich +3 more
Aging may modify the pharmacokinetic disposition and excretion of gentamicin, although drug dose adjustments in aged horses are uncommon in clinical practice. Since high-dose, once daily dosing of gentamicin is considered therapeutically most effective, a comparative single-dose study was conducted to evaluate the differences in pharmacokinetics between healthy young-adult (5-10 years) and geriatric (≥ 25 years) horses receiving 6.6 mg/kg gentamicin intravenously. Blood samples were collected at designated time-points following drug administration and frozen at -80°C until assayed by a validated immunoassay. Gentamicin plasma concentrations versus time plots were analyzed by noncompartmental analysis using commercial software (WinNonlin-v8.4). Baseline physical examination and hematological parameters did not differ between age groups, except for a lower mean bodyweight in the geriatric group (477 ± 4 kg vs. 402 ± 6 kg). None of the pharmacokinetic parameters were statistically different between age groups. The oldest geriatric horse (41 years) had a longer half-life and lower clearance of 5.3 h and 22.79 L/h, respectively, compared to a range of 1.39-2.56 h and 26.39-40.59 L/h for the remainder of the geriatric group (25-29 years). Further studies may be indicated in horses > 30 years old to determine if dose reduction is necessary in this population.
AQP4-Mediated Glymphatic Clearance: Sleep, Neurodegeneration, and the Translational Gap.
Neurosci Biobehav Rev
Maryline Santerre, Natalia Shcherbik, Bassel E Sawaya
One-third of adults in industrialized societies are chronically sleep-deprived. If current evidence linking sleep disruption to glymphatic failure extends to human populations, this may represent not merely a productivity concern but a significant and underappreciated risk factor for neurodegeneration at the population scale. The glymphatic system, a brain-wide perivascular network that clears soluble amyloid-beta, tau, alpha-synuclein, and other neurotoxic metabolites through astrocytic aquaporin-4 water channels, operates predominantly during slow-wave sleep and is impaired when sleep is disrupted. Glymphatic dysfunction has been documented across Alzheimer's disease, Parkinson's disease, traumatic brain injury, and normal aging, with evidence from animal models and post-mortem and neuroimaging studies suggesting self-amplifying cycles in which impaired clearance may accelerate protein accumulation, though causal directionality in humans remains to be established prospectively. This review synthesizes the current mechanistic understanding of glymphatic biology, the bidirectional relationship between sleep disruption and neurotoxic protein accumulation, and emerging evidence that chronic conditions that suppress slow-wave sleep, including obstructive sleep apnea, chronic obstructive pulmonary disease, and tinnitus, represent plausible but largely untested glymphatic risk factors for neurodegeneration that warrant prospective investigation. We critically evaluate therapeutic strategies targeting glymphatic enhancement, including slow-wave sleep augmentation, aquaporin-4 restoration, noradrenergic tone reduction, and cerebrospinal fluid flow augmentation, and argue that the absence of validated non-invasive glymphatic biomarkers remains a major translational limitation that warrants systematic prioritization.
Erythritol, sucrose, and sucralose elicit similar reward responses after flavor preference learning in healthy humans.
Physiol Behav
Emilie Flad, Fabienne Teysseire, Aleksandra Budzinska +7 more
Utilizing artificial low-caloric sweeteners as sugar alternatives remains controversial, as they provide sweet taste and the associated rewarding responses but fail to stimulate satiation. Erythritol, a non-caloric bulk sweetener, is able to stimulate the release of gastrointestinal (GI) satiation hormones, yet its influence on reward responses is inconclusive. The aim of this study was to investigate reward responses to erythritol, sucrose, and sucralose during and after flavor preference learning, and to explore the potential involvement of GI satiation hormones. In this randomized, double-blind, crossover study, 20 healthy participants (10 women, 10 men; mean ± SD; age: 25.8 ± 7.5 years, BMI: 22.3 ± 1.8 kg/m2) rated the reward responses (explicit wanting and liking) of three novel, neutral flavored beverages before and after pairing with erythritol, sucrose, or sucralose. GI satiation hormones (cholecystokinin, glucagon-like peptide-1) and parameters of glycemic control (glucose, insulin) were measured. After conditioning, explicit wanting and liking ratings increased, with no differences between the sweeteners. The release of GI satiation hormones and changes in glucose and insulin concentrations had no effect on the reward responses, which therefore might not be associated with flavor-nutrient learning (FNL) but rather with flavor-flavor learning (FFL). To conclude, beverages previously paired with erythritol appear to be equally liked as sucrose and sucralose.
rRGD3mu, a Triple-RGD Recombinant Peptide, Suppresses Malignant Phenotypes in Nasopharyngeal Carcinoma-Associated Models Through the Modulation of ITGB1-Associated FAK/AKT Signaling.
Int J Mol Sci
Qianhui Yuan, Fuxin Zhou, Xiaotong Li +6 more
Nasopharyngeal carcinoma-associated malignant epithelial models remain useful for exploring integrin-related therapeutic strategies. In this study, we evaluated the antitumor activity and potential mechanisms of rRGD3mu, a recombinant peptide with a triple-RGD architecture. Using CNE2 cells as the primary experimental model, we evaluated cell viability, colony formation, migration, invasion, adhesion, apoptosis-related marker expression, and EMT-associated molecular changes. In vivo efficacy was assessed using a CNE2 cell-derived BALB/c nude mouse xenograft model. rRGD3mu inhibited CNE2 cell viability, clonogenic growth, migration, invasion, and adhesion in a dose-dependent manner and suppressed xenograft tumor growth under the tested dosing schedule. Mechanistically, rRGD3mu promoted mitochondria-associated apoptosis, as indicated by an increased Bax/Bcl-2 ratio and caspase-9/3 activation, and modulated the expression of EMT-associated markers, including E-cadherin, N-cadherin, vimentin, and MMP2. Bioinformatic analysis and experimental validation suggested that ITGB1-containing integrin complexes might serve as important mediators and putative cellular engagement sites of rRGD3mu. rRGD3mu treatment reduced ITGB1 protein abundance and attenuated FAK/AKT signaling. ITGB1 knockdown partially mimicked the effects of rRGD3mu and reduced the additional cellular response to rRGD3mu treatment, supporting the substantial contribution of ITGB1-associated signaling. These findings provide preliminary mechanistic evidence that rRGD3mu suppresses malignant phenotypes in CNE2-based models, at least in part through modulation of ITGB1-associated FAK/AKT signaling.
Zinc Coordination by Thymosin β4: Structural Determinants and Functional Implications.
Int J Mol Sci
Joanna Izabela Lachowicz, Terenzio Congiu, Andrea Salis +1 more
Thymosin β4 (Tβ4) is a highly acidic, intrinsically disordered 43-amino-acid peptide with diverse biological functions, yet its interactions with metal ions remain poorly understood. In this study, we provide the first experimental demonstration that Tβ4 forms discrete Zn2+-bound adducts and undergoes Zn2+-induced aggregation under physiological pH conditions. Combining zeta potential analysis, dynamic light scattering (DLS), electrospray ionization mass spectrometry (ESI-MS), nuclear magnetic resonance (NMR) spectroscopy, and scanning electron microscopy with elemental mapping (SEM/EDS), we show that Zn(II) binding progressively neutralizes Tβ4's negative surface charge and triggers a sharp aggregation transition. ESI-MS unambiguously identifies Tβ4/Zn(II) complexes of peptide-to-zinc molar ratio 1:3, while DLS and SEM reveal the formation of compact, low-solubility supramolecular assemblies. NMR measurements support a metal-induced aggregation, confirming the absence of folding upon Zn(II) binding. By quantitatively comparing the experimentally determined critical aggregation concentration with physiologically observed extracellular Zn(II) ranges, we demonstrate that aggregation is unlikely in plasma or basal interstitial environments but may become feasible in Zn-rich microdomains, such as the synaptic cleft, where transient Zn(II) levels can exceed 1 μM. These findings introduce a previously unrecognized dimension of Tβ4 chemistry and suggest that a Zn(II)-mediated supramolecular assembly of Tβ4 could influence peptide behavior in neurological or inflammatory conditions characterized by elevated extracellular Zn(II). This work establishes a foundational biochemical framework for future studies aimed at elucidating the biological implications of Tβ4/Zn(II) complexation and aggregation in vivo.
Bergenin Suppresses Glycolysis and Malignant Progression in Breast Cancer via the IGF1R-MAPK Signaling Pathway.
Ann Clin Lab Sci
Minhui Fan, Qingyu Li, Renya Shuai +2 more
This study endeavors to unravel the effects and mechanisms of bergenin (Ber) in suppressing breast cancer (BC) progression through modulating the IGF1R-MAPK signaling pathway, using an integrative approach combining network pharmacology and bioinformatics.
Boerhaave's syndrome associated with glucagon-like peptide-1 receptor agonist use: a case report.
J Cardiothorac Surg
Jason M Aubrey, Chance Benner, Geoffrey T Lam
Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are increasingly prescribed for type 2 diabetes and weight loss, with well known gastrointestinal side effects including nausea, vomiting, and delayed gastric emptying. While mucosal injuries such as Mallory Weiss tears have been reported, full thickness esophageal perforation has not previously been described. We report the first documented case of Boerhaave's syndrome associated with GLP-1 RA use, highlighting the potential for rare but life threatening complications following abrupt reinitiation at high doses.
Evidence-informed guidance for the clinical use of oral semaglutide in obesity management.
Postgrad Med
Domenica Rubino, Sean Wharton, Michael G Knight +1 more
Oral semaglutide, the first oral glucagon-like peptide-1 (GLP-1) receptor agonist therapy approved for the treatment of type 2 diabetes, is now approved for obesity management and cardiovascular risk reduction in adults, demonstrating weight loss comparable to that of subcutaneous GLP-1 therapies, alongside improvements in cardiometabolic risk factors. The availability of oral semaglutide for the treatment of obesity provides healthcare professionals with additional opportunities to individualize therapy based on patient preferences, lifestyle, and clinical circumstances. However, the oral semaglutide formulation requires specific administration conditions to optimize absorption and effectiveness. Notably, oral semaglutide tablets should be taken first thing in the morning on an empty stomach with no more than half a glass of plain water (up to 120 mL or 4 fl oz), followed by 30 min before eating food, drinking additional fluids, or ingesting other oral medications. Person-centered clinical discussions between healthcare professionals (HCPs) and patients prior to treatment initiation are important to ensure patients understand administration requirements and why they are necessary, establish realistic expectations for obesity treatment targets, and cover approaches to maintain adherence. HCP-patient consultations should also include discussion of strategies to help patients minimize, prepare for, and manage adverse events. In this article, we provide practical guidance for incorporating oral semaglutide into obesity management, drawing on evidence from clinical trials, including the OASIS 4 trial, and the authors' clinical insights.
Neurovascular unit dysfunction in vascular cognitive impairment: Mechanisms, biomarkers, and translational strategies.
Exp Neurol
Christina Hoyer-Kimura, Meredith Hay
Vascular cognitive impairment and dementia (VCID) encompasses a heterogeneous spectrum of cognitive disorders driven by cerebrovascular pathology and represents a major contributor to late-life cognitive decline. VCID is highly prevalent and frequently coexists with Alzheimer's disease pathology. Despite this, it remains poorly defined in clinical practice and lacks approved disease-modifying therapies. Therapeutic development has been hindered by biological heterogeneity, challenges in patient stratification, and a historical emphasis on neurodegenerative targets that inadequately address vascular mechanisms. Increasing evidence implicates dysfunction of the neurovascular unit-including small vessel disease, chronic hypoperfusion, blood-brain barrier disruption, and neuroinflammation-as a central driver of vascular-mediated cognitive impairment and a unifying therapeutic target across diverse VCID phenotypes. In this review, we synthesize current understanding of VCID pathobiology with a focus on neurovascular unit dysfunction and emerging mechanism-based strategies aimed at restoring vascular and neurovascular homeostasis. We further examine translational considerations for targeting neurovascular signaling pathways, including endothelial stabilization, modulation of vascular inflammation, and preservation of blood-brain barrier integrity. As an illustrative example, we discuss preclinical evidence supporting Mas receptor agonism, including the glycosylated angiotensin-(1-7) analogue PNA5, as a potential approach to address vascular-mediated cognitive impairment. Finally, we explore implications for biomarker selection, patient enrichment, and early clinical trial design. Together, this framework highlights neurovascular dysfunction as a tractable therapeutic target in VCID and underscores the need for mechanism-driven approaches to address a substantial unmet clinical need.
Syringin Protects Against Doxorubicin-Induced Cardiotoxicity via Apelinr-Dependent Activation of the Nuclear Factor-Erythroid 2-Related Factor 2/Heme Oxygenase-1 Antioxidant Pathway.
Phytother Res
Yujiang Li, Ting Wang, Ming Shen +10 more
Cardiotoxicity induced by the chemotherapeutic agent Doxorubicin (Dox) is a major clinical challenge, primarily mediated by overwhelming oxidative stress. While Syringin (Syr) is known for its antioxidant potential, its efficacy and mechanism in the context of Dox-induced cardiotoxicity are not well defined. This study aimed to assess the therapeutic potential of Syr in alleviating Dox-induced cardiac injury and to elucidate its underlying molecular mechanism. The cardioprotective effect of Syr was evaluated in a Dox-induced mouse model of cardiotoxicity and in primary cardiomyocytes, with pravastatin (Prv, 10 mg/kg) serving as the positive control in the Syr dose-finding experiment. Cardiac function and myocardial strain were measured by advanced echocardiography using wall-tracking and speckle-tracking analyses. Network pharmacology was applied to identify downstream signaling pathways and molecular targets of Syr. Myocardial atrophy, antioxidant proteins, and oxidative stress markers were assessed by histology, Western blotting, and qRT-PCR. To validate the key molecular target, in vivo siRNA-mediated knockdown of the apelin receptor (APJ) was performed. Syr treatment significantly attenuated myocardial atrophy and suppressed oxidative stress. Syr also increased APJ expression, activated mechanosensitive PI3K/AKT phosphorylation, and restored fibroblast growth factor 21 (FGF21) homeostasis, thereby improving myocardial circumferential and longitudinal strain. Mechanistically, APJ silencing blunted Syr's ability to upregulate antioxidant proteins in Dox-exposed cardiomyocytes, and the benefits of FGF21 overexpression were lost. Consistently, APJ knockdown abolished Syr's protection against Dox-induced cardiotoxicity in vivo, eliminating its improvements in cardiac function and myocardial strain. Our study first demonstrates that Syr protects against Dox-induced cardiotoxicity by restoring the APJ/PI3K/AKT signaling axis, which subsequently enhances the nuclear factor-erythroid 2-related factor 2/heme oxygenase-1 (NRF2/HO-1) antioxidant response and maintains FGF21 homeostasis. These findings identify Syr as a promising natural compound for mitigating chemotherapy-induced cardiotoxicity and highlight the APJ as a novel therapeutic target.