Microglia are the predominant resident innate immune cells of the brain that maintain homeostasis and mitigate damage caused by injury and pathogens. Synthetic variants of host defence peptides, also termed antimicrobial peptides, are designed based on their endogenous counterparts and have been demonstrated to exhibit enhanced immunomodulatory activities, including an ability to selectively modulate the release of cytokines by monocytic cells. These peptides exert therapeutic benefits in a murine brain injury model, but it is unknown whether they can modulate microglial immune responses. We tested the effects of three host defence peptides, namely innate defence regulators (IDR)-1002, IDR-1018 and D-3006, on selected functions of BV-2 murine microglial cells, as well as differentiated HL-60 monocytic cells, which were used as a human model of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-dependent reactive oxygen species (ROS) production. It was demonstrated here that IDR-1002, IDR-1018 and D-3006 reduced the production of nitric oxide, tumor necrosis factor-α (TNF), ROS, and cytotoxic factors, depending on whether the cells were stimulated with lipopolysaccharide (LPS), interferon (IFN)-γ, or their combination. All three IDRs also reduced LPS-induced phagocytic activity of BV-2 microglia, while IDR-1018 and D-3006 increased this function in unstimulated cells, though our findings are limited to cell lines and require validation in primary or human microglia. By altering selected inflammatory, cytotoxic, and phagocytic readouts of microglial cells in a context-dependent manner, synthetic host defence peptides such as IDRs warrant further investigation as candidate modulators of neuroinflammation, including in animal models of relevant neurological disorders.
The glucose-dependent insulinotropic polypeptide receptor (GIPR) has emerged as a central target in next-generation anti-obesity drug development. Its pharmacology, however, presents an apparent paradox: sustained GIPR agonism and GIPR antagonism can both lower body weight, and both can augment weight loss produced by glucagon-like peptide-1 receptor (GLP-1R) agonism. For this structured narrative review, PubMed/MEDLINE and ClinicalTrials.gov were searched from database inception through 1 August 2026 using prespecified terms for receptors, interventions, obesity, and bariatric surgery to identify basic, translational, and clinical studies available. Retrieved records underwent staged title/abstract screening and full-text eligibility assessment. The evidence was integrated across three levels: selective GIPR modulation, combined GIPR and GLP-1R modulation, and applications after metabolic and bariatric surgery. Recent rodent studies support a working model in which long-acting GIPR agonism engages GABAergic and area-postrema-related circuits, whereas the added weight-lowering effect of GIPR antagonism in several GLP-1R-containing combination models depends on intact GLP-1R signaling and hypothalamic GIPR networks. These mechanisms remain incompletely validated in humans. Clinically, tirzepatide has demonstrated the efficacy of GIPR/GLP-1R co-agonism, whereas maridebart cafraglutide provides phase 2 evidence for GIPR antagonism combined with GLP-1R agonism; nevertheless, the efficacy of these multi-receptor agents cannot be attributed simply to a single GIPR component. Metabolic and bariatric surgery is discussed as a translational context in which altered incretin physiology limits direct extrapolation from nonsurgical obesity trials. Future studies should use stratified designs grounded in receptor pharmacology, brain-region specificity, type of bariatric procedure, and postoperative metabolic phenotype, while assessing fat mass, lean mass, hepatic fat, bone metabolism, gastrointestinal tolerability, hypoglycemia, and weight regain after treatment withdrawal.
Antimicrobial peptides (AMPs) have garnered considerable attention as promising alternatives to conventional antibiotics, resulting in extensive experimental and computational studies that have generated large volumes of data on peptide sequences, biological activities, structural features, and experimental conditions. To organize and facilitate the use of these data, several AMP databases have been developed; however, they differ markedly in scope, data organization, annotation depth, searchability, data accessibility, usability, and support for computational analysis. In this review, we critically compare five widely used general AMP databases—APD, CAMP, DBAASP, dbAMP, and DRAMP—by analyzing database publications and directly evaluating their current data content, web interfaces, search systems, analytical tools, and suitability for different research workflows. The comparison shows that no single database fully addresses all research needs, as the resources offer complementary strengths in biological annotation, sequence and family analysis, experimental activity data, computational discovery, and therapeutic-development information. These findings highlight the need for more standardized and interoperable database strategies that improve data consistency, annotation quality, searchability, tool reliability, and the comparison, integration, and reuse of AMP data in experimental and computational research.
Sulfakinin (SK) peptides are the insect members of the ancient cholecystokinin (CCK)/gastrin superfamily, defined by a sulfated tyrosine near the C-terminus and a C-terminally amidated heptapeptide core, the modifications essential for receptor activity. Although SK peptides share C-terminal similarity with vertebrate CCK-8 and gastrin, this homology is pharmacologically incomplete: both Drosophila sulfakinin receptors cluster in an arthropod-specific clade absent from vertebrate receptor families, and cross-species bioassays confirm receptor-level incompatibility. This review synthesizes current knowledge of SK structure, receptor biology, signal transduction, and physiological function across insect orders to evaluate the SK-receptor axis with emphasis on factors that may guide future pest-management applications. SKR complement ranges from one gene in Hymenoptera and Lepidoptera to two paralogous receptors in several Diptera and Coleoptera, arising from independent lineage-specific duplications. Both Ca²⁺ and cAMP second messenger arms are engaged in species-dependent combinations governed by G-protein coupling selectivity. SK peptides regulate meal termination, fat body lipid and glycogen metabolism, ecdysteroid-mediated moulting, reproductive behaviour, and agonistic signalling, with these functions partitioned among specific receptor subtypes, neural circuits, and peripheral tissues. In laboratory studies of economically significant pest species, RNAi-mediated SK-receptor silencing disrupts feeding, development, and fecundity, whereas biostable peptidomimetics represent a promising but still exploratory chemical approach. Receptor coupling identity in phytophagous crop pests, validated field-compatible dsRNA delivery, and ecological safety remain major unresolved barriers to practical application.
BACKGROUND:Type 2 diabetes (T2D) often leads to diabetic gastroenteropathy characterized by gastrointestinal motility disorders, mucosal damage, and oxidative stress. Neurotensin (NT), a gastrointestinal peptide, modulates mucosal healing and metabolic regulation, but its role in diabetic GI dysfunction remains unclear. METHODS:A streptozotocin (STZ) + nicotinamide (NAD) rat model was used to induce a non-obese T2D phenotype. Male Sprague Dawley rats were assigned to four groups (n = 8/group): Control, STZ, STZ + NT, and STZ + NT + SR-48692 (NTR1 antagonist). Systemic metabolic parameters, serum biochemical markers, gastric and ileal histopathology, oxidative stress markers (MDA, GSH, MPO, luminol and lucigenin chemiluminescence), and neurotransmitter levels (dopamine, serotonin, norepinephrine) were evaluated. Gastrointestinal function was assessed by intestinal transit, visceromotor reflex responses, and isolated organ bath analysis of gastric and ileal smooth muscle contractility. RESULTS:Diabetes induction caused significant hyperglycemia, dyslipidemia, hepatic and renal dysfunction, accompanied by marked gastric and ileal structural injury, including mucosal disruption, reduced glycoprotein content, and altered NT immunoreactivity. These changes were associated with increased oxidative stress, inflammatory activity, and disturbances in monoaminergic signaling. Functionally, diabetic rats exhibited impaired intestinal transit, reduced visceral sensory responses, and diminished cholinergic contractility in gastric and ileal smooth muscle. NT treatment significantly attenuated hyperglycemia, improved serum metabolic abnormalities, restored mucosal architecture, reduced oxidative stress, and improved gastrointestinal motility and contractile function. Most protective effects were abolished by SR-48692 co-administration, supporting a predominantly NTR1-dependent mechanism. CONCLUSION:NT ameliorates diabetes-induced GI dysfunction and systemic metabolic disturbances primarily via NTR1 signaling, suggesting the NT/NTR1 axis as a potential therapeutic target for diabetic gastroenteropathy.
