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peptide science.

Quantitative 99mTc-Pyrophosphate SPECT/CT evaluation of tafamidis response in a case of transthyretin cardiac amyloidosis.

Asia Ocean J Nucl Med Biol

Yoichi Otomi, Hideki Otsuka, Ryosuke Kasai +7 more

Transthyretin cardiac amyloidosis (ATTR-CA) is increasingly recognized as a cause of heart failure in elderly patients. Noninvasive diagnosis with technetium-99m pyrophosphate (99mTc-PYP) scintigraphy has become established, but quantitative approaches for therapy monitoring remain under investigation. We present a case of wild-type ATTR-CA in an 82-year-old man treated with tafamidis. Baseline echocardiography showed concentric left ventricular hypertrophy with preserved ejection fraction, impaired global longitudinal strain, and elevated B-type natriuretic peptide (BNP). Planar and SPECT/CT imaging with 99mTc-PYP demonstrated diffuse myocardial uptake (grade 3, H/CL 1.97). Quantitative analysis with GI-BONE software yielded SUVmax 4.2, amyloid deposition volume (AmyDV) 122 cm³, and total amyloid uptake (TAU) 313. Endomyocardial biopsy confirmed wild-type ATTR. After 18 months of tafamidis therapy, symptoms persisted with further GLS impairment and BNP elevation, while echocardiographic wall thickness remained increased. In contrast, repeat PYP imaging showed reduced uptake (grade 2, H/CL 1.64) with markedly decreased quantitative indices (SUVmax 2.3, AmyDV 2 cm³, TAU 4). This case demonstrates that volumetric indices can capture substantial therapy-related changes, although discordance with functional and biomarker findings highlights the need for integrated assessment. Quantitative 99mTc-PYP SPECT/CT may serve as a promising tool for therapy monitoring in ATTR-CA.

Case of postoperative diabetes insipidus following cervical decompressive laminectomies.

Surg Neurol Int

Cecilia Kehinde Okunlola, Margaret Olufemi Ibikunle, Abiodun Idowu Okunlola +4 more

Postoperative diabetes insipidus (DI) is rare, involving the hypothalamic-pituitary axis following cervical spine surgery.

Amylin Coexisting With Peptide YY (PYY) and Amylin/PYY Cells Correspond to Subpopulations of Glucagon- and Glucagon-Like Peptide-1-Immunoreactive Cells in the Japanese Eel (Anguilla japonica) Pancreas.

Anat Histol Embryol

Hirohumi Suzuki, Toshiharu Yamamoto

The distribution of amylin-like substances was investigated by immunohistochemistry in the pancreas of the Japanese eel (Anguilla japonica). Amylin-immunoreactive cells were observed in pancreatic islets. These immunostaining profiles were not observed by the preabsorption of the anti-amylin serum with synthetic amylin, indicating that the serum specifically recognized eel amylin-like peptide. Almost all amylin-immunoreactive cells were immunopositive for peptide YY, suggesting that amylin and peptide YY co-secreted from the islet cells might participate in the modulation of insulin and glucagon secretion in the pancreatic islets. In addition, weakly glucagon-immunopositive cells, but not densely glucagon-immunopositive cells, also corresponded to amylin-immunoreactive cells. The subpopulation of glucagon-immunoreactive and glucagon-like peptide-1-immunoreactive cells was also immunopositive for peptide YY. These results suggest that amylin and peptide YY, and also presumably glucagon-like peptide-1, are co-secreted from the amylin/peptide YY cells, and these three peptides modulate food intake through the central nervous system in addition to intrainsular functions.

Analysis of the efficacy and safety of liraglutide, semaglutide, and tirzepatide for the treatment of overweight and obesity: a systematic review and network meta-analysis.

J Endocrinol Invest

Wiktoria Pałka, Paweł Moćko, Katarzyna Śladowska +2 more

The rapid rise in overweight and obesity worldwide underscores the need for comparative evidence on long-term pharmacotherapy. The recent introduction of a 7.2 mg maintenance dose of semaglutide warrants particular attention. We assessed the efficacy and safety of glucagon-like peptide-1 (GLP-1) and GLP-1/glucose-dependent insulinotropic polypeptide (GIP) receptor agonists-liraglutide, semaglutide, and tirzepatide-focusing on the incremental value of semaglutide 7.2 mg.

Adrenal insufficiency diagnosis: new approaches to indeterminate baseline cortisol.

Curr Opin Endocrinol Diabetes Obes

Maria Ortega, Natalia Fretes Oviedo, Ricardo Correa

Adrenal insufficiency is a potentially life-threatening condition requiring timely diagnosis. Baseline morning cortisol remains the initial diagnostic test; however, indeterminate values (3-15 μg/dl) necessitate dynamic testing, which is costly and labor-intensive. This review summarizes recent advances in diagnostic approaches for patients with indeterminate baseline cortisol levels.

Human neuronal cells SH-SY5Y as an in vitro model to study Neospora caninum infection and innate immune modulation.

Vet J

Natalia Plá, Mercedes M Burucúa, Dadin P Moore +4 more

Neospora caninum causes significant losses due to abortions in cattle worldwide. The parasite can establish persistent infections in the central nervous system (CNS). Innate immune recognition, primarily mediated by Toll-like receptors (TLRs), and the expression of cytokines and antimicrobial peptides, such as cathelicidins, during N. caninum infection in neuronal cells remains undefined. This work studied the ability of N. caninum to infect and replicate in the CNS using an in vitro model for neurotropic infections in human neuroblastoma (SH-SY5Y) cells. We showed that N. caninum established productive infections in SH-SY5Y cells, and that the parasite can invade, replicate, and cause cell lysis. Infections with N. caninum induced a time-dependent modulation of the key components of innate immunity, TLR7 and CAMP, in SH-SY5Y cells. At the onset (24hours post-infection), N. caninum decreased TLR7 expression, while CAMP expression was increased. The TLR7-dependent signalling pathway modulated by N. caninum infection included increased MyD88 expression and decreased IRF7 expression. In conclusion, the human neuroblastoma cell line SH-SY5Y was susceptible to N. caninum infection and showed modulation of the innate immune response during infection.

Efficacy and Hypoglycaemia Outcomes With Once-Weekly IcoSema Versus Comparators in Individuals With Type 2 Diabetes by Kidney and Liver Function: A Post Hoc Analysis of the COMBINE 1-3 Trials.

Diabetes Obes Metab

Linong Ji, Jonas Dahl Andersen, Malik Benamar +4 more

This post hoc analysis of COMBINE 1-3 assessed efficacy and hypoglycaemia outcomes with IcoSema (once-weekly combination therapy of basal insulin icodec and semaglutide [a glucagon-like peptide-1 analogue]) versus comparators in adults with type 2 diabetes (T2D) by kidney and liver function subgroups.

Tirzepatide and the risk of atherosclerotic cardiovascular events: population based cohort study.

BMJ

Nils Krüger, Sebastian Schneeweiss, Shirley V Wang

To estimate the magnitude of reduction in major adverse cardiovascular events (MACE) that would be observed in clinical practice from adding tirzepatide to standard of care treatment.

Surgery on Patients Taking Glucagon-Like Peptide-1 Receptor Agonists.

Adv Surg

Claire B Rosen, Denise W Gee

This article begins by providing historical insight into the discovery, development, and use of glucagon-like peptide-1 receptor (GLP-1R) agonist medications in the treatment of type 2 diabetes and obesity. Next, the mechanism of action and impacts of GLP-1R agonists are discussed, along with an overview of the Food and Drug Administration-approved GLP-1R agonists currently on the market. Comparison in effects on weight loss of the available GLP-1R agonists is briefly discussed, along with its use in the context of bariatric surgery. Finally, perioperative considerations for surgical patients using GLP-1R agonists are reviewed along with suggested recommendations.

Amylin: A Multi-Functional Pancreatic Hormone-A Review.

Diabetes Obes Metab

Christelle Le Foll, Thomas A Lutz

Amylin is a pancreatic beta-cell hormone that sits at a systems hub connecting key aspects of energy metabolism. Amylin physiologically controls satiation, slows gastric emptying and limits postprandial glucagon release, while its actions also link homeostatic eating controls with reward driven behaviours via defined central nervous system pathways. Further, at least under certain conditions, aggregating amylin exerts a strong pathophysiological impact on the destruction of pancreatic beta-cells in Type 2 diabetes mellitus (T2D), providing a plausible explanation for why a T2D-like disease entity is only observed in a few mammalian species. This review will provide a brief summary of selected aspects of our current understanding of the biology of amylin and outlines how this knowledge has recently been translated into effective pharmacotherapy for obesity and diabetes, including long-acting analogs combination approaches with other peptide hormones.

Beyond Neurodegeneration: Systemic Confounders of Blood Neurofilament Light Chain in Aging and Their Implications for Neurological Biomarker Interpretation.

Mech Ageing Dev

Giulia Bonvini, Davide Sattin, Nunzio Iraci +5 more

Unlike younger populations, older individuals often live with multiple systemic conditions that may influence neurofilament light chain (NfL) levels beyond true neuroaxonal injury, complicating its interpretation as a pure marker of neuronal damage. While prior work has examined determinants of blood NfL, none has specifically addressed its contextualization in the geriatric multimorbid setting. This narrative review critically examines the main non-neurological determinants of circulating NfL in older adults focusing on age, renal function, BMI, glycemic dysregulation, cardiovascular disease, and chronic hypoxia and discussing their clinical implications. Renal dysfunction and BMI appear to act as pharmacokinetic modifiers, altering NfL concentrations through reduced clearance and plasma volume dilution, respectively, without necessarily reflecting increased neuronal injury. In contrast, aging, dysglycemia, cardiovascular disease, and hypoxia may function as biologically active confounders, potentially contributing to neuroaxonal damage through neuronal attrition, microvascular injury, cerebral hypoperfusion, and oxidative stress. This distinction carries clinical implications: pharmacokinetic confounders call for adjusted reference ranges, while biologically active confounders represent true sources of neurological vulnerability warranting independent attention. Blood NfL levels in the geriatric population mirror complex neuro-systemic interactions requiring an integrated interpretive approach. Longitudinal monitoring and elderly-specific multivariate models could improve NfL's reliability as a tool in geriatric neurology.

The role of GLP-1 and GIP receptor agonists in the treatment of diabetes and obesity.

Pharmacol Res

Robert Roskoski

Owing to the therapeutic success of glucagon-like peptide-1 receptor (GLP-1R) and glucose-dependent insulinotropic polypeptide receptor (GIPR) agonists in the management of diabetes and obesity, the pharmacology of these drugs and their receptors has engendered considerable interest. GLP-1 and GIP are incretin hormones so named owing to their ability to increase insulin secretion. Currently FDA-approved GLP-1 peptide receptor agonists used for the management of diabetes include liraglutide, semaglutide, and injectable dulaglutide. Agonists approved for the management of obesity include liraglutide and semaglutide, which have injectable and oral formulations. Tirzepatide is a combined GLP-1 and GIP receptor peptide agonist given by injections that is FDA-approved for the management of type 2 diabetes, obesity, and obese patients with a weight-related comorbidity such as obstructive sleep apnea. Orforglipron is a small molecule orally bioavailable medicine that is approved for the treatment of obesity. Retatrutide is an injectable peptide agonist of GLP-1R, GIPR, and the glucagon receptor that is undergoing clinical trials for the management of obesity and diabetes. The peptides per se undergo rapid degradation in the body. To overcome the need for frequent injections, molecular engineering strategies were used to prolong circulating half-lives. Peptide fatty acid acylation represents one strategy for extending the half-life of peptides by co-opting the role of albumin as a fatty acid transporter thereby retaining peptides in the systemic circulation. A universal side effect of all GLP-1 receptor agonists includes nausea and vomiting. Consequently, the dosage is escalated sequentially over a period of weeks to mitigate these side effects.

Fabrication and characterization of biocompatible BPC-157 based chitosan hydrogel.

3 Biotech

Monika Arunim, Misika Dagar, Rakesh Solanki +4 more

Multifunctional hydrogels are essential for advanced biomedical applications. In this study, CH/BPC composite hydrogel was fabricated and characterized for their physicochemical properties. The formulation exhibited a porous structure, analyzed through scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Fourier-transform infrared spectroscopy (FTIR) showed the presence of hydrogen bond between BPC-157 peptide and chitosan backbone, indicating successful peptide incorporation within the hydrogel matrix. The composite hydrogel exhibited a balanced water vapor transmission rate (2,270 ± 35 g/m2 /day), along with remarkable properties of injectability, self-healing capability, and adhesiveness. Furthermore, the hydrogel demonstrated excellent encapsulation (98.9 ± 0.8%) of BPC-157, with release profile of 81.2 ± 2.9% within 24 h. In addition, the CH/BPC hydrogel demonstrated potent antibacterial efficacy, achieving up to 45.9% (Escherichia coli) and 65.0% (Staphylococcus aureus) inhibition. The fabricated hydrogel also showed a hemolysis rate of less than 5%, indicating acceptable hemocompatibility. Collectively, these findings indicate that CH/BPC hydrogel possesses desirable physicochemical and antibacterial characteristics, highlighting their potential as multifunctional hydrogel for future biomedical applications.

Effects of Oral Semaglutide on Dietary Intake and Body Composition in Japanese People With Type 2 Diabetes: A Prospective Observational Study in Clinical Practice.

Endocrinol Diabetes Metab

Mika Sawada, Naoko Nakanishi, Masakazu Aihara +7 more

Glucagon-like peptide-1 receptor agonists are effective glucose-lowering agents with established benefits on body weight and cardiometabolic outcomes. However, their precise effects on body composition and dietary intake patterns, including food group consumption and macronutrient energy distribution, particularly in clinical settings, remain incompletely understood.

Effect of Oral Semaglutide on Cardiovascular Outcomes in Type 2 Diabetes by Extent of Vascular Disease.

J Am Coll Cardiol

Matthew A Cavender, Nikolaus Marx, Sharon L Mulvagh +18 more

Weight Loss-Dependent Changes in Body Composition and Bone Health in People With Obesity and Type 1 Diabetes Treated With Liraglutide, Semaglutide, or Tirzepatide.

Diabetes Metab Res Rev

Ebaa Al Ozairi, Mohammad Irshad, Jumana Alkandri +3 more

This study examined changes in body composition and bone mineral density (BMD) over 12 months in people with obesity and type 1 diabetes (T1D) treated with a GLP-1 receptor agonist alone (GLP-1RA) or a dual glucose-dependent insulinotropic polypeptide (GIP/GLP-1RA).

A clinical and experimental investigation of liraglutide effects on the brain-kidney axis.

Sci Adv

Michael P Greenwood, Mohammed I Alotaibi, Soledad Bárez-López +4 more

Glucagon-like peptide-1 receptor agonists elicit diuresis and natriuresis in humans and rodents. However, little is known about their interactions with the bodies hormonal systems that control fluid homeostasis. We performed a single center, open-label, before-and-after study and discovered that liraglutide reduces plasma arginine vasopressin (AVP) levels in healthy humans. By quantitative proteomic and phosphoproteomic investigation of the rat pituitary gland, we detail time- and sex-dependent modifications to synaptic proteins mediated by liraglutide. We developed an in vitro AVP luciferase assay to assess the impact of synaptic protein phosphorylation on AVP secretion. We used this assay to identify synaptic protein phosphosites that influence AVP release and liraglutide-mediated sex differences in AVP release. Investigation of AVP downstream signaling pathways in the kidney revealed posttranslational changes to the crucial AVP-regulated water channel aquaporin 2. Thus, glucagon-like peptide-1 receptor agonist modulation of AVP release may be responsible for cardiovascular and renal changes observed in patients.

Targeted Clearance of Senescent Endothelium by GPNMB-Specific CAR-T Cells.

J Immunol Res

Peijie Yu, Jie Du, Yan Liu +1 more

Endothelial cells (ECs) serve as crucial components of blood vessels and are vital for preserving vascular health in humans. The aging of these cells significantly accelerates vascular aging. Factors released by aging ECs serve as key initiators of arterial dysfunction and various cardiometabolic diseases. As a result, the targeted removal of aging ECs from injured tissues could reduce these issues and potentially improve lifespan. In this research, we explored the therapeutic capabilities of chimeric antigen receptor (CAR)-T cells designed to focus on senescent cells as potential senolytic agents. We identified GPNMB, a transmembrane glycoprotein, as a protein characterized by extensive expression during cellular senescence. Our findings demonstrate that CAR-T cells specifically targeting GPNMB can efficiently remove senescent cells in vitro. In addition to this, the engineered CAR-T cells significantly clear replicative and doxorubicin (Dox)-induced senescent human umbilical vein ECs (HUVECs). Notably, these CAR-T cells successfully eradicated senescent HUVECs within a Matrigel matrix implanted subcutaneously in mice, thereby creating a simulated in vivo environment that mimics physiological conditions. The findings emphasize the possibilities of CAR-T cells in treating EC senescence.

Assessing pedestrian responses to autonomous and personal mobility robots in crowded public spaces.

Sci Adv

Dominik Wojcikiewicz, Aude Billard, Diego Paez-Granados

Robots increasingly share spaces with people, supporting delivery services and mobility for the aging populations, yet their ability to share space comfortably lacks understanding and benchmarks for designers and policy-makers. We compared human-robot (HRI) and human-human (HHI) interactions across four real-world crowd datasets spanning Europe, North America, and Asia, using a unified pipeline to detect interactions, stratify by crowd density, and model pedestrian behavior. Local motion patterns (speed, acceleration, and jerk) remained closely matched between HRI and HHI across all densities. In contrast, proxemics diverged, with effects that grew approximately linearly with robot speed and weakened under higher crowding: In the dataset with the faster navigating robot, pedestrians maintained about 0.23 meters more clearance around the robot than around other pedestrians under less crowded conditions and about 0.05 meters more under more crowded conditions, while in the dataset with the predominantly stationary robot, the corresponding differences were small and inconsistent across crowding levels. The main conclusions were robust to parameter variations and remained stable across a broad range of motion-processing and interaction-labeling settings. Our findings provide density- and speed-aware benchmarks for proxemics in social robot navigation and empirically grounded targets for design, evaluation, and modeling across robotics and urban mobility.

A machine learning-derived aging-related gene signature for diagnosing HCV cirrhosis: Insights into immune microenvironment and therapeutic targets.

Comput Biol Chem

Yueping Yao, Min Zhou, Zhihan Yan +4 more

While direct-acting antiviral (DAA) therapies effectively cure most chronic hepatitis C virus (HCV) infections, patients with pre-existing cirrhosis remain at risk for disease progression. Cellular senescence and immune dysregulation drive persistent liver injury post-clearance, but reliable biomarkers and therapeutic targets remain scarce.