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Neuropeptide Y Receptor Modulators in Gut Physiology and Therapy.
Curr Protein Pept Sci
Kalyani R Thombre, Nikita D Rahangdale, Krishna Radheshyam Gupta +1 more
Gut-brain communication depends on neuropeptides and hormones, and the Neuropeptide Y (NPY) family, which includes NPY, Peptide YY (PYY), and Pancreatic Polypeptide (PP), plays an important role. These peptides also affect gastrointestinal (GI) motility, secretion, nutrient uptake, and intestinal development. Diseases, including irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), gastroparesis, and obesity, are attributed to disruptions in this signaling axis. In this review, the physiological and pathological functions of NPY and its receptor subtypes (Y1, Y2, Y4, Y5) in the GI tract, the therapeutic potential of Pharmacological and natural modulators of this pathway are evaluated.
Chicoric acid enhanced brain cholesterol efflux and reduced Aβ pathology via LXR-ABCA1 signaling in Alzheimer's models.
Neurotherapeutics
Daiyue Li, Yu Zhang, Ruonan Wang +6 more
Alzheimer's disease (AD) is one of the most pressing public health challenges in an aging world. However, effective therapeutic strategies are still lacking. Imbalance in lipid homeostasis is a key driver of AD. Given the established link between dysregulated lipid metabolism and amyloid-beta (Aβ) aggregation, we investigated whether chicoric acid (CA), a dietary polyphenol with reported lipid-modulating properties, could mitigate Aβ pathology by modulating lipid metabolism in 5xFAD transgenic mice. In the brain, we found that CA upregulated the expression of liver X receptor Beta (LXR-β) and ATP-binding cassette transporter A1 (ABCA1) in 5xFAD mice. Through this pathway, it promoted apolipoprotein E (ApoE) lipidation and enhanced the expression of Aβ-clearance proteins (IDE and LRP1). Notably, in the periphery, CA reshaped the gut microbiota in 5xFAD mice, which reduced serum neurotoxic bile acid levels and preserved the integrity of the peripheral Aβ clearance system. Together, our study first demonstrated that CA globally regulated lipid homeostasis to alleviate Aβ pathology by coordinating cerebral cholesterol efflux with peripheral bile acid metabolism. The findings facilitated exploring active compounds from traditional Chinese medicine that may reduce Aβ deposition by targeting lipid metabolism pathways.
MOTS-c primes adrenal cortex metabolism without directly driving steroidogenesis.
Folia Histochem Cytobiol
Malgorzata Blatkiewicz, Kacper Kaminski, Marta Sobalska-Kwapis +4 more
Mitochondrial open reading frame of the 12S rRNA type-c (MOTS-c), a 16-amino acid mitochondrial-derived peptide, regulates cellular metabolism through AMPK and mTOR signaling and exerts protective effects across multiple endocrine tissues. However, its role in adrenal physiology remains unexplored. We hypothesized that MOTS-c establishes "steroidogenic readiness" by priming metabolic pathways rather than directly activating hormone synthesis.
Synergistic effects through targeting the PI3K and IGFR pathways in treating lung cancer carrying activation alterations along the PI3K pathway.
Transl Oncol
Mohamed Abd El-Salam, Wu Chen, Yan Tang +9 more
Alterations in the PI3K/AKT pathway occur in over 60 % of lung squamous cell carcinoma and approximately 20 % of lung adenocarcinoma, driving tumor progression and therapeutic resistance. While PI3K-targeted therapies suppress proliferation in PIK3CA-mutant non-small cell lung cancer (NSCLC), their clinical impact is limited due to compensatory activation of insulin receptor (IR) and insulin-like growth factor-1 receptor (IGF-1R) signaling. This study aimed to determine whether dual blockade of PI3K and IR/IGF-1R signaling could overcome this adaptive resistance.
Mitochondrial transfer as a therapeutic target for peripheral neuropathy.
Trends Mol Med
Junlin Wei, Fang Wang
Satellite glial cells transfer mitochondria to sensory neurons via myosin 10-dependent tunneling nanotubes. Ji et al. show that this transfer is impaired in diabetic neuropathy, causing energy failure. Restoring it via cell or mitochondrial transplantation alleviates pain and promotes nerve regeneration, revealing a new therapeutic strategy for peripheral neuropathy.
Childhood Obesity and Cardiac Risk in Youth: Emerging Challenges Toward 2050.
Clin Nutr ESPEN
Nikunja Kishor Mishra
Pediatric obesity is increasing at an alarming rate, affecting over 381 million children worldwide and emerging as a critical public health issue. According to World Health Organization (WHO) 2016, 40% of adults are overweight and 13% are obese, highlighting obesity's persistence throughout life. Childhood obesity significantly heightens the risk of adult obesity and cardiovascular diseases (CVD) such as atherosclerosis and coronary artery disease, potentially leading to a global health crisis by 2050. Genetic predispositions identified through genome-wide association studies (GWAS) contribute to elevated body mass index (BMI), yet lifestyle factors reduced physical activity, prolonged screen time, and consumption of high-calorie, low-nutrient foods remain key drivers. This study aim is to explore the Real-world data (RWD) on childhood obesity from major countries, prevalence, risk factors, and cardiovascular consequences of pediatric obesity, evaluating public health initiatives, lifestyle interventions, and therapeutic strategies to address this growing concern. Data collected from PubMed, Scopus, and Springer databases reveal that childhood obesity is closely linked to hypertension, dysglycemia, dyslipidemia, and other cardiovascular disorders (heart attack, arrhythmias and stroke). The WHO Global Action Plan on Physical Activity 2018-2030 (GAPPA) emphasizes urgent preventive measures. Current management strategies include lifestyle modification, pharmacotherapy, and bariatric surgery. Glucagon-like peptide-1 (GLP-1) receptor agonists such as semaglutide and liraglutide are effective for weight management but commonly cause gastrointestinal adverse effects. The SURMOUNT-5 trial demonstrated superior weight-loss outcomes with tirzepatide, with a similar gastrointestinal safety profile. Emerging therapies including cagrilintide plus semaglutide, oral agents such as orforglipron and danuglipron, and the triagonist retatrutide may improve adherence and accessibility; however, these agents remain investigational and are currently under clinical evaluation. Despite promising advancements, gene therapy for pediatric obesity remains in the experimental phase. Overall, addressing childhood obesity requires multifaceted interventions combining public health initiatives, behavioral changes, and novel therapeutic strategies to mitigate cardiovascular risks and promote sustainable health outcomes.
Disparities in GLP-1 and GIP responses to small intestinal glucose infusion in individuals with well- and poorly-controlled type 2 diabetes.
Diabetes Res Clin Pract
Yixuan Sun, Cong Xie, Michelle Bound +6 more
Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are key regulators of glucose homeostasis in health and type 2 diabetes (T2D). Whether their secretion is influenced by antecedent glycaemic control in T2D remains unclear. This study compared GLP-1 and GIP responses to intraduodenal glucose infusion between individuals with well- and poorly-controlled T2D.
Maternal Nutrition and Hypothalamic Programming of Offspring Metabolic Health.
J Nutr
Smita Mall, Busayo Oladun, Min-Hyun Kim
The hypothalamus plays a central role in regulating metabolism by integrating hormonal and nutrient-derived signals to maintain energy homeostasis across the life span. Maternal nutritional status during critical windows of development is a major environmental factor that can permanently alter this regulation. Both maternal overnutrition and undernutrition have been shown to disturb circulating leptin, insulin, and glucagon-like peptide-1 (GLP-1), and to disrupt the normal development of hypothalamic nuclei implicated in energy balance. Experimental and clinical studies indicate that these insults miswire proopiomelanocortin (POMC) and neuropeptide Y/ agouti-related peptide (NPY/AgRP) pathways, alter leptin and insulin receptor signaling, trigger neuroinflammation, glial and vascular changes, and are accompanied by enduring epigenetic alterations, including DNA methylation and chromatin remodelling at genes such as Pomc, Npy, Mc4r, Lepr and Insr. Together, these adaptations establish new set points for appetite, energy expenditure, and glucose regulation, thereby increasing the lifelong risk of obesity and type 2 diabetes in the offspring. In this narrative review, we synthesize evidence from animal models and human studies linking maternal nutrition to hypothalamic programming via leptin, insulin, and GLP-1. We also highlight major gaps, including limited data on GLP-1 in maternal undernutrition, the specific role of individual micronutrients, and the timing and reversibility of hypothalamic programming, to inform future mechanistic, translational, and preventive research.
The Glymphatic System and Meningeal Lymphatics: Current Understandings and Future Perspectives.
MedComm (2020)
Hangzhe Sun, Haonan Fan, Yuhang Zhou +6 more
The central nervous system (CNS) maintains homeostasis and immune surveillance through a recently defined brain-wide clearance network: the glymphatic-lymphatic axis. This system couples the intramural glymphatic pathway, responsible for convective fluid transport and parenchymal waste removal, with the meningeal lymphatic vessels (MLVs), which serve as the critical efferent route to the peripheral immune system. This review delineates the structural and functional foundations of each component, their regulatory dynamics, including the roles of sleep and aging, and their synergistic interplay in maintaining fluid balance, clearing metabolic waste, and facilitating neuroimmune communication. Mounting evidence identifies the dysfunction of this integrated axis as a common pathological mechanism across a spectrum of neurological disorders. We highlight its pivotal role in three key paradigms: acute injury (stroke), chronic proteinopathy (Alzheimer's disease, AD), and autoimmune dysregulation (multiple sclerosis, MS), where impaired clearance and maladaptive immune responses are central, recurring themes. The review critically evaluates emerging translational strategies aimed at therapeutically modulating this axis, including pharmacological targets (VEGF-C, Piezo1 agonists), noninvasive neuromodulation (photo-biomodulation, PBM), and surgical interventions (lymphaticovenous anastomosis, LVA). This synthesis positions the glymphatic-lymphatic axis as a fundamental physiological network and a pivotal target for novel interventions, outlining key future research directions in neurology.
Cellular senescence: Between protection and pathologies.
J Physiol Pharmacol
I Klak, A Ptak-Belowska, G Krzysiek-Maczka
Cellular senescence is a stable and irreversible state of proliferative arrest triggered by diverse stressors, inclh3uding DNA damage, oncogenic signaling, oxidative stress, and metabolic imbalance. Once regarded as a culture artifact, senescence is now recognized as a fundamental biological program that governs tissue homeostasis, development, aging, and disease. Based on its origin, senescence can be divided into two principal categories: damage-induced, encompassing replicative, oncogene-induced, and therapy-induced forms, and developmentally programmed, which orchestrates tissue patterning and remodeling during embryogenesis. These processes converge on the activation of p53/p21 and p16/RB tumor suppressor axes, sustained DNA damage response (DDR), and the establishment of the senescence-associated secretory phenotype (SASP). Acute senescence serves beneficial roles in tumor suppression, wound healing, and embryonic morphogenesis by transiently activating SASP-mediated immune clearance. However, persistent senescence becomes detrimental, promoting chronic inflammation, tissue dysfunction, and cancer progression. Within the tumor microenvironment, chronic SASP signaling driven by nuclear factor kB (NF-κB), CCAAT/enhancer-binding protein beta (C/EBPβ), and Signal Transducer and Activator of Transcription 3 (STAT3) fosters epithelial-to-mesenchymal transition (EMT), invasion, and therapy resistance. Therapy-induced senescence (TIS) often leads to polyploidization and the emergence of polyploid giant cancer cells (PGCCs) that can escape arrest, regenerate proliferative progeny, and drive tumor relapses. Thus, senescence represents a biological paradox: a protective, transient process that maintains tissue integrity but, when unresolved, transforms into a driver of aging and malignancy. Understanding the molecular determinants, distinguishing beneficial from pathological senescence is crucial for developing targeted senotherapies.
Neuroinflammation in stroke-A review of implications for precision immunomodulation.
Neuroscience
Tatyana Zharikova, Elizaveta Petrova, Igor Makarov +3 more
Stroke remains a leading cause of mortality and long-term disability worldwide, and secondary injury mechanisms-particularly neuroinflammation-continue to limit functional recovery despite advances in reperfusion therapies. Post-stroke neuroinflammation is not a static or uniformly deleterious process but a temporally evolving and spatially heterogeneous continuum shaped by cellular transcriptional plasticity, metabolic reprogramming, and systemic modifiers such as aging and comorbidities. Across hyperacute, acute, subacute, and chronic phases, microglia, astrocytes, and neurovascular unit components undergo dynamic state transitions that may either exacerbate neuronal injury or promote debris clearance, angiogenesis, synaptic remodeling, and circuit reorganization. Emerging transcriptomic and spatial profiling studies challenge simplified polarization frameworks and highlight the need for multidimensional models of immune activation. We propose a precision-based framework in which neuroinflammation is interpreted through the integration of temporal dynamics, cellular heterogeneity, and responsiveness to rehabilitation. Within this context, the concept of an "immune window" underscores the importance of aligning immunomodulatory interventions with phase-specific inflammatory states to enhance neuroplasticity without suppressing reparative signaling. Although targeted strategies-including cytokine inhibition, metabolic reprogramming, gene-editing approaches, and biomarker-guided stratification-show mechanistic promise, translational progress has been limited by model heterogeneity, blood-brain barrier constraints, safety concerns, and insufficient validation in aged and comorbid populations. Future advances will depend on biomarker-driven patient stratification, phase-informed trial design, and integration of immunomodulation with reperfusion and rehabilitation. Rather than indiscriminate suppression, calibrated and context-aware immunoregulation may represent the most rational path forward in optimizing stroke recovery.
Comparative Proteomic Analysis of the Secretome of Control and BRAF/MEK Inhibitor-Resistant Melanoma Cells.
J Proteome Res
Aleksandra Simiczyjew, Magdalena Surman, Magdalena Kot +2 more
Treatment based on BRAF/MEK kinase inhibitors is one of the most commonly used methods in advanced melanoma therapy, but patients often develop resistance to treatment. Treatment-resistant cells can affect other cancer cells and the tumor microenvironment through the factors that they secrete. Therefore, this study aimed to examine the protein composition of the secretome of cells resistant to vemurafenib (a BRAF inhibitor) and cobimetinib (a MEK inhibitor) and to compare it with that of nonresistant cells. Proteomic analysis, followed by gene ontology (GO) analysis, identified many differences in resistant melanoma cells' secretomes compared to controls (nonresistant). Many proteins upregulated in resistant melanoma cells compared to their nonresistant variants were directly related to cancer progression and associated with cell adhesion, actin cytoskeleton, matrix organization, proteolysis, and drug resistance. Proteins secreted by resistant melanoma cells can undoubtedly influence the surrounding microenvironment in a way that promotes the formation of a pro-tumor niche. Among the proteins secreted in significantly higher amounts by resistant cells (compared to the control group), which may be potential biomarkers or therapeutic targets in melanoma, plasminogen activator inhibitor 1, thymosin beta-4, clusterin, interleukin-6, superoxide dismutase, and selected matrix metalloproteinases can be distinguished.
Centriolar satellites regulate CEP350 mRNA localization and centrosome amplification.
bioRxiv
Abraham Martinez, Chad G Pearson
Messenger RNAs (mRNAs) accumulate at centrosomes in mitosis and interphase, yet the mechanisms governing their localization and the functional significance of centrosomal localization remain poorly understood. Here, we investigate the regulation and function of the centrosome-localized mRNA, CEP350 . We find that CEP350 mRNA localizes to centrosomes during S phase via the centriolar satellite protein CEP131 and the RNA binding protein (RBP) Unkempt (UNK), in a microtubule (MT)-dependent manner. CEP131 and UNK stabilize CEP350 mRNA to maintain CEP350 mRNA steady-state levels. Furthermore, CEP131 and UNK promote normal CEP350 protein levels at centrosomes. CEP350 is required for PLK4-induced centriole overduplication but is less important for canonical centriole duplication. Moreover, CEP131, UNK, and CEP350 are important for centrosome amplification in triple-negative breast cancer cells. Together, these findings reveal a centriolar satellite-RBP pathway regulating CEP350 mRNA localization to centrosomes.
Plant-derived exosome-like vesicles enhance exercise-induced muscle recovery and sleep quality.
Nutr Res
Emrah Aykora, Damla Aykora
Exercise-induced muscular stress triggers a complex cascade of adaptive responses, including micro-injury, inflammation, activation of satellite cells, mitochondrial remodeling, and myofibrillar repair. The efficiency of recovery processes is crucial for athletic performance, especially among elite athletes, where rapid restoration of muscle function, reduction of inflammation, and improved sleep quality influence training results. Beyond traditional recovery methods, EVs and, more recently, plant-derived exosome-like nanovesicles (PELNs) have emerged as promising bioactive mediators of intercellular communication and tissue regeneration. PELNs contain various biomolecules such as lipids, proteins, small RNAs, and plant-specific metabolites that may affect oxidative stress, inflammatory signaling, and cellular repair pathways. While most research has focused on mammalian or cell-line sources, growing evidence indicates that PELNs may improve muscle regeneration and recovery through cellular modulation and enhanced sleep-related recovery. Notably, PELNs represent a multi-target strategy that may simultaneously modulate neuroendocrine pathways involved in sleep regulation and metabolic-inflammatory mechanisms governing skeletal muscle repair. By influencing circadian rhythm signaling, mitochondrial dynamics, and redox homeostasis, PELNs may bridge the sleep-muscle recovery axis, an emerging concept in exercise physiology. This dual regulatory capacity distinguishes PELNs from conventional recovery interventions and highlights their innovative and translational potential in sports science. This review aims to compile current evidence linking PELNs to exercise-induced muscle recovery, highlighting potential mechanisms, including the regulation of inflammatory and redox balance, microRNA-driven signaling, and neurometabolic adaptation. By combining insights from exercise physiology and molecular regenerative biology, we propose that PELNs offer a natural approach to enhancing recovery and performance in athletes.
Semaglutide as a potential tool in pre-lung transplant weight loss optimization.
JCEM Case Rep
Roshaneh Ali, Holly Keyt, Carolina Solis-Herrera +1 more
Patients with end-stage lung disease go through an extensive screening process prior to transplant. Obesity and uncontrolled type 2 diabetes mellitus (T2DM) are unfavorable risk factors that lead to poor outcomes. We present the case of a 69-year-old man with stage IV chronic obstructive pulmonary disease (COPD) on chronic oxygen, T2DM on insulin, and class II obesity (reference range, body mass index [BMI], 35.0-39.9) who underwent pre-lung transplant evaluation. He had a BMI of 38.05, surpassing the institutional transplant eligibility criteria of BMI <32. The patient was initiated on semaglutide for weight loss. After 6 months, the patient's BMI decreased to 30.5, losing 25 kg and qualifying him for transplant. However, given substantial improvements in respiratory status, the pre-lung transplant committee deferred waitlisting. After 16 months of treatment, the patient lost a total of 35.17 kg, his forced vital capacity improved from 44% to 82%, and he was weaned off oxygen. Chronic hypoxia and corticosteroids make weight management challenging for COPD patients. This case demonstrates the use of semaglutide for rapid weight loss and improved respiratory function in patients with end-stage lung disease, emphasizing its emerging potential in pre-lung transplant optimization.
Sex-specific metabolic responses to glucagon receptor agonism and modulation of the FGF21-glucagon axis in female mice.
J Physiol
Christoffer Merrild, Valdemar Brimnes Ingemann Johansen, Christoffer Clemmensen +1 more
Glucagon receptor agonism, particularly when combined with incretin analogues, is currently being explored as a treatment for obesity to improve cardiometabolic health, given glucagon's key role in regulating energy homoeostasis. However, male-biased preclinical studies limit our understanding of sex-specific responses to glucagon receptor activation, especially regarding fibroblast growth factor 21 (FGF21), a major downstream effector of glucagon signalling. To test whether responses to glucagon receptor agonism are sex dependent and modulated by FGF21, we compared a long-acting glucagon analogue (LA-Gcg) with the GLP-1 analogue semaglutide in diet-induced obese male and female mice. We then used female Fgf21 knockout (KO) mice to probe the role of the FGF21-glucagon axis in the response to glucagon receptor agonism. LA-Gcg induced greater weight loss, reduced food intake and more strongly altered hepatic gene expression in males, whereas semaglutide effects were comparable between sexes. LA-Gcg impaired glucose tolerance more severely in females than in males. This impairment was exacerbated in female Fgf21 KO mice, despite similar reductions in body weight between genotypes. Notably, FGF21 deficiency potentiated diet-induced obesity in females but had minimal impact under chow diet, fasting or voluntary exercise. Collectively, these findings reveal that both sex and FGF21 modulate metabolic responses to glucagon-based therapies, emphasizing the importance of including female models in preclinical metabolic research to better predict therapeutic efficacy. KEY POINTS: Biological sex is known to affect metabolism, yet this variable remains largely underexplored in metabolic research. In males, glucagon's metabolic benefits often involve another hormone, FGF21 (fibroblast growth factor 21), but this relationship is largely unstudied in females. A long-acting glucagon (LA-Gcg) treatment caused less weight loss in obese female mice, failing to reduce their food intake, unlike in males. LA-Gcg also worsened glucose tolerance in females. Female mice lacking the Fgf21 gene were more susceptible to diet-induced obesity; although LA-Gcg treatment still reduced their weight and cleared liver fat, the absence of FGF21 worsened the drug-induced glucose intolerance. Our findings highlight sex-specific differences in metabolic responses to glucagon, emphasizing the need to consider sex as a key variable in the development of glucagon-based therapies.
Vitreous hemorrhage in a patient on tirzepatide: Coincidence or drug induced?
Oman J Ophthalmol
Sitara Azeem, Lujain Al Bulushi, Buthaina Isa Sabt
Tirzepatide is a synthetic polypeptide classified as glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 receptor agonist. It stimulates insulin secretion from the pancreas and helps lower blood sugar levels in patients with type 2 diabetes mellitus. It also reduces appetite and helps in weight reduction management. We report a case of unilateral vitreous hemorrhage in a middle-aged woman on tirzepatide for weight loss. A 55-year-old female, nondiabetic, on tirzepatide for weight loss presented with sudden visual loss in the right eye while being on tirzepatide. Her ocular history is known for angle-closure glaucoma status postsurgical peripheral iridectomy in both eyes many years back. Her medical history is notable for palpitations and is currently managed with beta blockers. At presentation, the best-corrected visual acuity in the right eye was 0.16 and 1.0 in the left eye. Fundus examination revealed vitreous hemorrhage in the right eye. Vitreous hemorrhage spontaneously resolved and uncorrected visual acuity improved to 1.0 over a period of four months. The key point to be conveyed from this case is the need for more studies into whether there is a causal relationship between tirzepatide and vitreous hemorrhage in nondiabetic patients and to promote caution when administering tirzepatide.
Benchmarking size-exclusion chromatography columns for the analysis of therapeutic peptides and model oligonucleotides.
J Chromatogr A
Mathias Buff, Alexandre Goyon, Kelly Zhang +1 more
Eleven modern size-exclusion chromatography (SEC) columns, including prototype columns designed to minimize non-specific interactions, were systematically evaluated for the analysis of peptides and oligonucleotides. Column physical properties and chromatographic performance were assessed under various mobile phase conditions. Notably, a reduced plate height close to 1 was achieved for one prototype column, representing a marked improvement over typical SEC performance (2 < hmin < 3). Mobile phase composition was optimized to balance chromatographic efficiency and analyte denaturation. The most denaturing conditions (30 % acetonitrile, 0.1 % trifluoroacetic acid) provided the best performance for linear, macrocyclic, disulfide-constrained, and lipid-conjugated peptides by effectively suppressing hydrophobic and ionic interactions. Columns with pore sizes ≥ 100 Å showed optimal performance, with UP-SW2000, Biozen dSEC-1, and BioCore SEC-120 columns (100-125 Å) yielding the best results. Column and mobile phase selection were particularly critical for hydrophobic peptides such as liraglutide and semaglutide; for these analytes, a phosphate-based mobile phase containing 20 % isopropanol was proposed to limit denaturation and potentially enable the characterization of non-covalent aggregates. For oligonucleotides, mobile phase composition had a limited impact, whereas stationary phase chemistry was decisive. Only two columns (UP-SW2000 and ACQUITY Premier SEC 125 Å) provided acceptable separations, enabling resolution of n-2 and n-3 shortmer impurities of 20-mer linear and structured oligonucleotides with resolutions close to 1. Coupling two 150-mm SEC columns in series further enhanced shortmer separation within 30 min.
GLP-1 receptor agonists and immune checkpoint inhibitor therapy: a narrative review on mechanistic and clinical evidence.
Future Oncol
Connor Frey
Obesity paradoxically increases sensitivity to immune checkpoint inhibitors (ICIs) despite elevating cancer risk, creating a clinical opportunity where metabolic dysfunction may generate a target-rich immune microenvironment. However, immunosuppressive mechanisms, including regulatory T-cells, myeloid-derived suppressor cells, and pro-inflammatory macrophages, can limit durable anti-tumor responses. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) extend beyond metabolic comorbidity management, functioning as metabolic-immunologic adjuvants capable of reprogramming the tumor microenvironment in obese patients receiving ICIs. A literature search was conducted in PubMed/MEDLINE through December 2025 using MeSH headings related to glucagon-like peptide-1 receptor agonists and immune checkpoint inhibitors. Mechanistically, GLP-1R signaling activates cAMP-PKA-AMPK pathways that suppress NF-κB-driven inflammation and promote macrophage repolarization, improving CD8 T-cell metabolic fitness, enhancing central memory formation, and reducing lipid-induced T-cell exhaustion. Real-world observational data across renal cell carcinoma, non-small cell lung cancer, colorectal cancer, and neuroendocrine neoplasms suggest improved overall survival, fewer immune-related adverse events, and lower cardiometabolic complications with concurrent GLP-1RA and ICI therapy. Pharmacovigilance concerns regarding pancreatitis, ICI-induced diabetes, and immune-related toxicities remain incompletely characterized. This review critically appraises mechanistic insights, real-world evidence, and safety considerations, proposing a translational-clinical research agenda to prospectively validate GLP-1RAs as rational adjuncts to checkpoint blockade.
Sensing performance of ScTiO3 film-based EIS arrays through co-sputtering for pH sensing and heart failure biomarker monitoring.
Talanta
Tung-Ming Pan, Chia-Yu Kuo, Jim-Long Her +1 more
In this work, a ScTiO3 sensing film array was fabricated on a p-type Si substrate using a co-sputtering technique and subsequently integrated into electrolyte-insulator-semiconductor (EIS) platforms for both pH sensing and N-terminal pro-B-type natriuretic peptide (NT-proBNP) detection, a clinically important biomarker for heart failure (HF) diagnosis. To evaluate the structural, interfacial, and sensing characteristics, the films underwent RTA at temperatures between 600 and 800 °C. Extensive material characterization, including X-ray diffraction, X-ray photoelectron spectroscopy, Auger electron spectroscopy, transmission electron microscopy, and atomic force microscopy, revealed a strong correlation between the microstructural evolution of the ScTiO3 films and their sensing performance. Superior sensing characteristics were observed in the film annealed at 700 °C, which recorded the highest sensitivity (65.07 mV/pH) alongside impressive stability metrics, including a 0.26 mV/h drift rate and 1.2 mV hysteresis. Furthermore, to enable specific NT-proBNP detection, the ScTiO3 surface was first functionalized with APTES and then conjugated with EDC/NHS-activated antibodies, facilitating precise antigen-antibody interactions. The resulting ScTiO3-based array EIS biosensor demonstrated excellent analytical performance, delivering a high sensitivity of 10.84 mV/pCNT-proBNP over a wide dynamic detection range from 10-4 to 106 pg/mL. Collectively, these results highlight the strong potential of a ScTiO3 sensing film array as high-performance platforms for reliable pH monitoring and advanced biomedical diagnostics, particularly for sensitive and accurate NT-proBNP detection in HF applications.