The living record of
peptide science.

Editorial: Lifetime achievements in avian physiology.

Front Physiol

Colin G Scanes, Sandra G Velleman

Renalase knockdown inhibits proliferation of mouse satellite cells.

Mol Biol Rep

Yuri Kato, Katsuyuki Tokinoya, Kai Aoki +1 more

Cy3-Conjugated Biocompatible Polymer Nanoparticles for Long-Term Mitochondrial Imaging.

Chembiochem

Souma Kawashima, Mitsuo Inui, Izumi Takaba +2 more

The cyanine dye Cy3 has recently gained attention as a membrane potential-responsive, small-molecule mitochondrial imaging probe. However, the efficiency of Cy3 for mitochondrial imaging is relatively low, as diffusion of Cy3 leads to staining of the entire cell over time. This problem could be due to the passive diffusion-based, concentration-dependent uptake into cells and molecular diffusion inherent to small-molecule compounds. Therefore, we hypothesized that polymer chemistry approach could be applied to overcome these limitations. In this study, we designed modified dye in which biocompatible polymers were covalently attached to Cy3. This enabled control of intracellular dynamics that could not be achieved using Cy3 alone. Toward this objective, we synthesized a Cy3-modified amphiphilic dextran with phenylalanine ethyl ether side chains. The amphiphilic polymers self-assembled into nanoparticles. We then characterized the synthesized polymer in terms of intracellular uptake and the mitochondria translocation capacity of the nanoparticles using human skeletal muscle satellite cells. Our approach changed the cellular internalization process, resulting in increased cellular uptake efficiency, enhanced mitochondrial imaging capability, and improved mitochondrial retention over the long term. These nanoparticles, which can stain mitochondria regardless of cell type, have the potential to become a new type of mitochondrial imaging reagent.

Thymalfasin combined with immune checkpoint inhibitors in the treatment of non-small cell lung cancer: A retrospective study on efficacy, safety, and immunological function.

Pak J Med Sci

Peipei Wang, Xiaojing Zhang, Cheng Xiang +2 more

To evaluate the efficacy, safety, and immunomodulatory effects of thymalfasin in combination with different immune checkpoint inhibitor (ICI)-based regimens in patients with advanced driver gene-negative non-small cell lung cancer(NSCLC).

From Maternal Exposure to Fetal Risk: Unraveling the PFAS Exposure Pathway and Its Placental Toxicity Mechanism.

Environ Sci Technol

Yurou Gao, Zichen Kuang, Qian S Liu +2 more

Per- and polyfluoroalkyl substances (PFAS) have triggered a global crisis due to their severe toxicities and widespread occurrence in human populations. Notably, PFAS is frequently detected in maternal blood, placental tissue, and umbilical cord blood, indicating direct fetal exposure to PFAS through the maternal-fetal interface. As the central organ regulating nutrient exchange, endocrine signaling, and immune balance, the placenta is particularly vulnerable to PFAS exposure, and its dysfunction is linked with various adverse pregnancy outcomes, including fetal growth restriction, low birth weight, preterm birth, preeclampsia, etc. However, existing knowledge on PFAS-induced placental dysfunction remains fragmented, typically addressing their occurrence, transplacental transfer, specific mechanistic targets, or epidemiological evidence in isolation. This review synthesizes evidence tracing the entire trajectory of PFAS exposure─from maternal uptake and distribution in the bloodstream to placental accumulation, transplacental passage, and fetal exposure. It further highlights how PFAS may interfere with key processes of placental development, including angiogenesis and vascular remodeling, trophoblast migration and invasion, lipid metabolism, hormone production, and establishment of the maternal-fetal immune microenvironment, which provides mechanistic explanations linking PFAS exposure to adverse pregnancy outcomes. By integrating transplacental behaviors, mechanistic insights, epidemiological findings, and methodological advances, this review offers a comprehensive perspective on PFAS-induced placental toxicity and presents new directions for assessing maternal-fetal health risks.

Semaglutide Treatment in Young Adults Living With Type 2 Diabetes: A Post Hoc Analysis From the SUSTAIN and PIONEER Clinical Trials.

Diabetes Obes Metab

Francesco Zaccardi, Vanita R Aroda, Ecenur Guder Arslan +6 more

Young adults (aged ≤ 40 years) are underrepresented in clinical trials that investigate interventions for those living with Type 2 diabetes (T2D). This study evaluated the efficacy of semaglutide treatment in young adults with T2D by examining the effects on HbA1c and body weight (BW) during the SUSTAIN and PIONEER programmes compared to placebo and active comparators, according to age at study enrolment. This study also assessed aggregated safety data across age subgroups.

Insights from changes in NDEV biomarkers of metabolism: Effects of PPARγ and GLP1 receptor agonists on brain metabolism.

J Clin Endocrinol Metab

Audrey Evers, Kathleen Watson, Fahim Abbasi +4 more

Insulin resistance (IR) is implicated in central nervous system disorders, including depression and Alzheimer's disease (AD).

Effect of Incretin-Based and Nonpharmacologic Weight Loss on Body Composition : A Systematic Review.

Ann Intern Med

John A Batsis, Alessandro Gavras, Danae C Gross +12 more

Incretin-based therapies induce substantial weight loss and are widely prescribed; disproportionate losses in fat-free mass (FFM) and skeletal muscle are a concern.

Use of Glucagon-Like Peptide-1 Receptor Agonists and Risk of Parkinson's Disease: Scandinavian Cohort Study.

Diabetes Obes Metab

Arvid Engström, Henrik Svanström, Anders Hviid +8 more

To investigate the association between use of GLP-1 receptor agonists and incident Parkinson's disease.

From collapse to comeback: Luteolin rejuvenates nucleus pulposus progenitor cells via SIRT1/ATF5-UPRmt to reverse intervertebral disc degeneration cascade.

Stem Cell Res Ther

Huofeng Wu, Shuangjia Zai, Xuan You +8 more

Intervertebral disc degeneration (IVDD) is a major contributor to low back pain (LBP) and one of the foremost causes of disability worldwide. Oxidative stress-induced senescence of nucleus pulposus progenitor cells (NPPC) and mitochondrial dysfunction are key drivers of IVDD. The mitochondrial unfolded protein response (UPRmt), orchestrated by the Silent Information Regulator 1 (SIRT1)-Activating Transcription Factor 5 (ATF5) axis, plays a pivotal role in maintaining mitochondrial proteostasis. However, its involvement in IVDD remains insufficiently characterized. Luteolin (Lut), a naturally occurring flavonoid with well-documented antioxidant and anti-senescence properties, has emerged as a promising disease-modifying candidate.

Spleen-Targeting Delivery of the Liposomal Antigen via an RBC-Based Platform for Cancer Immunotherapy.

ACS Appl Mater Interfaces

Shengmin Yang, Yanning Bao, Nana Meng +12 more

Efficient delivery of tumor antigens to the spleen remains a challenge for systemic cancer vaccination. Although nanoparticles provide versatile platforms for antigen delivery, intravenous administration often results in preferential sequestration by the reticuloendothelial system, leading to dominant hepatic accumulation and limited spleen-targeting. Here, leveraging the intrinsic splenic clearance property of senescent red blood cells (RBCs), we developed an RBC-based liposomal antigen delivery system by covalently conjugating antigen- and adjuvant-coloaded liposomes onto the RBC surface, thereby inducing senescence-like changes in the carrier RBCs and endowing the modified RBCs with enhanced splenic sequestration. Following intravenous administration, the RBC-liposome vaccine delivery system achieved highly efficient accumulation in the spleen, where the antigen was effectively internalized by splenic immune cells, leading to T cell activation and induction of robust immune responses. This delivery system demonstrated significant therapeutic efficacy in a melanoma-bearing mouse model with a remarkable tumor inhibition rate of 96.5%. Our study might offer a promising strategy for antigen spleen-targeting delivery in cancer immunotherapy.

Intraventricular hemorrhage, suspected EBV reactivation, and TBA-positive epilepsy after deep cervical lymphovenous anastomosis in Alzheimer's disease: a case report.

Front Aging Neurosci

Tiantian Jiang, Fang Yan, Bin Liu +6 more

Lymphovenous anastomosis (LVA) is emerging as a potential surgical intervention to ameliorate cervical lymphatic outflow and enhance glymphatic clearance in Alzheimer's disease (AD). However, the spectrum of neurological sequelae associated with this procedure remains poorly characterized. We report the case of a 67-years-old male with amyloid PET-confirmed AD who underwent bilateral deep cervical LVA. Twenty-three days postoperatively, he presented with high-grade fever and altered consciousness. Head CT revealed acute hemorrhage in the posterior horn of the left lateral ventricle (∼2 mL). Cerebrospinal fluid (CSF) analysis demonstrated lymphocytic pleocytosis and significantly elevated protein levels; the fluid was uniformly bloody, confirming intraventricular hemorrhage. Plasma metagenomic next-generation sequencing (mNGS) identified Epstein-Barr virus (EBV), with serology supporting reactivation. Following antiviral and empirical antibiotic therapy, the patient's condition stabilized, and the hemorrhage resolved. Four months postoperatively, he developed new-onset generalized seizures. Despite negative results from a conventional autoimmune encephalitis antibody panel in both serum and CSF, a tissue-based assay (TBA) proved positive in both samples. Seizures were successfully controlled with levetiracetam. This case suggests a potential association between invasive lymphatic procedures and a hemorrhage-infection-immune cascade in highly vulnerable AD patients with preexisting metabolic and neurodegenerative risk factors.

Spatial coupling of enlarged perivascular spaces and white matter lesions across the Alzheimer's disease continuum.

Front Neurosci

Serena Tang, Pamela Thropp, Isabella Hausle +2 more

Emerging evidence suggests that impaired waste-clearance systems contribute to Alzheimer's disease pathogenesis, yet the etiology of clearance dysfunction markers, such as enlarged perivascular spaces, remains unclear. Because enlarged perivascular spaces and white matter lesions are both consequences of microvascular injury involving neuroinflammation and impaired cerebrovascular function, we hypothesize that these markers may be spatially coupled through local interstitial fluid stagnation, where impaired perivascular clearance associates with white matter injury.

Context‑dependent duality of the apelin/elabela‑APJ system in diabetes and its complications (Review).

Int J Mol Med

Zhenyuan Han, Jiale Zhang, Min Shi +4 more

The apelin/elabela‑apelin receptor (APJ) signaling system is a key regulator of metabolic homeostasis and cardiovascular function in diabetes mellitus. However, its therapeutic application is complicated by its functional divergence: the system exerts protective effects in some tissues while driving pathology in others. The present review examined these distinct roles, focusing on how the biological outcome depends on the specific ligand, disease stage and tissue microenvironment. It discussed the molecular mechanisms underlying this divergence, as well as the varying roles of the same receptor at different stages of the same disease. Finally, it evaluated emerging therapeutic strategies, such as stabilized analogs and biased agonists, proposing that precise targeting of the APJ conformational landscape offers a pathway to move beyond glycemic control toward multi‑organ protection in diabetes.

Targeting the Apelin-APJ Axis: A Promising Strategy to Mitigate Anthracycline-Induced Cardiotoxicity.

Cardiovasc Toxicol

Varsha G Desai

Anthracycline-induced cardiotoxicity remains a major clinical challenge, often progressing to heart failure years after therapy. Conventional cardioprotective agents, including angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and beta-blockers, are widely used to preserve cardiac function; however, their effectiveness is limited by their inability to comprehensively address the complex, multifactorial pathophysiology of anthracycline-induced cardiotoxicity. This underscores the critical need for more effective and mechanism-based cardioprotective strategies that directly target the underlying molecular mechanisms, particularly oxidative stress and mitochondrial dysfunction. In recent years, the apelin-APJ signalling axis has attracted increasing attention as a potential therapeutic target in cardiovascular diseases owing to its multifaceted biological actions, including positive inotropy, vasodilation, anti-inflammatory, anti-fibrotic, anti-apoptotic, antioxidant, and pro-angiogenic effects. These pleiotropic actions are primarily mediated through the activation of key signalling pathways such as phosphoinositide 3-kinase/protein kinase B, extracellular signal-regulated kinases 1/2, and AMP-activated protein kinase. Given that these signalling cascades are disrupted during anthracycline-induced cardiotoxicity, pharmacological activation of the apelin-APJ axis may represent a promising avenue to mitigate anthracycline-associated cardiac injury with greater efficacy than conventional therapies. While native apelin isoforms (apelin-12, -13, -17, and [Pyr¹]apelin-13) are limited by their short half-lives, chemically modified analogues such as LIT01-196 and apelin-17(A2) exhibit enhanced stability and efficacy, with demonstrated cardioprotective effects in preclinical cardiovascular models and patients with chronic heart failure. However, their therapeutic potential in anthracycline-induced cardiotoxicity remains largely unexplored. This review highlights its promise as a novel cardioprotective strategy for mitigating anthracycline-induced cardiotoxicity.

Glucose-dependent dynamics of glucagon, cortisol and adrenocorticotropic hormone before and after gastric bypass.

J Endocr Soc

Vasileios Chronopoulos, Maria C Kjellsson, Martin H Lundqvist

Roux-en-Y gastric bypass (RYGB) improves glucose homeostasis beyond weight loss, but the underlying mechanisms remain incompletely understood. Counter-regulatory hormones such as glucagon, ACTH, and cortisol are key components of glucose regulation.

Apoptosis induction and migration suppression through regulation of IGF-1R/FoxO signaling pathways in Panc1 pancreatic cancer cells by hAMSCs secretome: An in vitro cell-based therapy.

Cancer Treat Res Commun

Fatemeh Safari, Mohammad Rasouli, Mana Alavi

Pancreatic cancer often referred to as the "king of cancers," is a disease with no symptoms and lacks effective therapy. Current treatment options for pancreatic cancer have not been successful, highlighting the need for new therapeutic avenues with minimal side effects and improved effectiveness. In recent years, new cell-based therapies using stem cells or their derivatives have shown promise in treating various diseases, including cancer. Here, we aimed to explore the impact of the secretome of human amniotic mesenchymal stem cells (hAMSCs) on Panc1 pancreatic cancer cells, focusing on the insulin-like growth factor 1 receptor (IGF-1R)/FoxO signaling pathways. To achieve this, we developed a co-culture system utilizing 6-well plates transwell. After 72 h, cell death and cell invasion in hAMSCs-treated Panc1 cells were assessed using Western blot, Scratch assay, and DAPI staining. Our results showed an increase in the expression levels of AKT, AMPK, FasL, and cleaved caspases 3/9, while there was a decrease in FoxO, IGF-1R, PI3K, 14-3-3, p-FoxO, MMP3, Integrin α3, and Integrin β6 expression. These findings suggest that hAMSCs' secretome promotes cell death and inhibits cell invasion in Panc1 cells, indicating its potential as a novel targeted therapy approach for pancreatic cancer.

Glucagon-Like Peptide-1 Receptor Agonists: Their Therapeutic Potential in Cystic Fibrosis.

Adv Ther

Theodoros Panou, Evanthia Gouveri, Djordje S Popovic +1 more

Cystic fibrosis (CF) is a monogenic disorder leading to pulmonary disease, pancreatic insufficiency and cystic fibrosis-related diabetes (CFRD). Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are now being investigated in people with cystic fibrosis (pwCF) and CFRD. To date, their therapeutic potential has been almost exclusively studied in case reports or case series. These agents improved glycated haemoglobin (HbA1c) and continuous glucose monitoring (CGM) parameters. Benefits were also observed in weight reduction, particularly for subjects on cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy elexacaftor/tezacaftor/ivacaftor (ETI). However, discordant results have also been reported. Moreover, GLP-1RAs have improved pulmonary function, even following lung transplantation. Importantly, the dual glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor agonist tirzepatide has also yielded favourable outcomes. Finally, preliminary evidence suggests potential inhibition of bone resorption, pointing to a therapeutic perspective in cystic fibrosis-related bone disease (CFBD). However, potential adverse events should not be ignored. These include risk of acute pancreatitis, nausea/vomiting, nutritional depletion, bowel dysmotility and distal intestinal obstruction syndrome, as well as others. Adverse events should be addressed with caution, and dose adjustments may be useful. Large prospective multicentre studies are now required to validate these outcomes and to suggest implications for clinical practice.

Effects of tirzepatide, a dual GIP and GLP-1 receptor agonist, on blood pressure, cardiac function, and sympathetic nervous system in stroke-prone spontaneously hypertensive rats.

Hypertens Res

Yoshiyasu Ono, Keisuke Shinohara, Hiroka Nakashima +13 more

Tirzepatide, a dual agonist for glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors, has shown robust efficacy in treating diabetes and obesity, and in obese patients with heart failure with preserved ejection fraction (HFpEF), it reduced weight, lowered blood pressure, and improved outcomes. However, its cardiovascular effects in non-obese, non-diabetic hypertension remain unclear. We investigated the impact of tirzepatide on blood pressure, cardiac function, and sympathetic nervous system activity in stroke-prone spontaneously hypertensive rats. Starting at 8 weeks of age, rats received tirzepatide (TZP, 25 nmol/kg, every two days), vehicle (VEH), or pair-fed vehicle (VEH-PF) to control for differences in food intake for 4 weeks. Tirzepatide significantly reduced food intake and body weight. Contrary to prior clinical observations, tirzepatide elevated mean blood pressure (197.4 ± 16.6 vs. 153.7 ± 5.4 mmHg at Day 28; TZP vs. VEH-PF, n = 9 vs. 8; p < 0.05) and increased heart rate, accompanied by left ventricular hypertrophy, myocardial fibrosis, and impaired diastolic function. Sympathetic activation was evident, with higher plasma norepinephrine levels and increased ΔFosB expression-a marker of sustained neuronal excitation-in the parvocellular paraventricular nucleus and the rostral ventrolateral medulla. Moreover, ΔFosB expression was increased in anorexigenic proopiomelanocortin neurons within the hypothalamic arcuate nucleus, which reduce feeding and have been implicated in promoting sympathetic excitation. These findings point to a central mechanism underlying increased sympathetic outflow. In conclusion, tirzepatide increased blood pressure and sympathetic activity in hypertensive rats without cardiac protection, highlighting context-dependent cardiovascular actions. Tirzepatide increased blood pressure, impaired LV diastolic function, and induced cardiac hypertrophy and fibrosis, as well as sympathetic overactivation in SHRSP.

Glucagon-Like Peptide-1 Receptor Agonists in Patients with Heart Failure with Reduced Ejection Fraction.

ESC Heart Fail

Joseph Kassab, Mark H Drazner, Jennifer T Thibodeau

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) improve cardiovascular outcomes in obesity and HFpEF; however, their safety and efficacy in heart failure with reduced ejection fraction (HFrEF) remain uncertain.