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Roles of insulin-like growth factor 1 receptor in growth regulation in 15q26 deletion and duplication syndrome.
Biomed Rep
Kexin Yu, Xin Xu, Bo Liu +12 more
The 15q26 deletion and duplication syndromes are rare chromosome diseases with growth deviation and structural anomalies such as facial abnormality, cardiac malformation and hand/foot/skeleton malformations. Insulin-like growth factor 1 receptor (IGF1R), located on chromosome 15q26, is key for pre- and postnatal growth. The present study aimed to determine whether IGF1R serves as a key factor in growth regulation in 15q26 deletion and duplication syndromes. Patients with 15q26 deletions and duplications enrolled in the China Neonatal Genomes Project (CNGP) were recruited. A systematic review of 15q26 deletion and duplication cases was performed, followed by meta-analysis to evaluate the roles of IGF1R and three other genes [myocyte enhancer factor 2A (MEF2A), leucine-rich repeat kinase 1 (LRRK1) and nuclear receptor subfamily 2 group F member 2] involved in growth regulation. A total of 10 eligible patients from the CNGP, including seven with deletions and three with duplications, were identified. The literature search and screening yielded 78 patients with 15q26 deletions and 10 with 15q26 duplications. Clinical features observed in >70% of the patients in the deletion group were facial abnormalities, developmental delay, short stature and hand/foot/skeleton malformations, whereas the duplication group exhibited facial abnormality, hand/foot/skeleton malformation and speech development delay. In 15q26 deletion, three candidate genes were associated with an increased risk of short stature: IGF1R [odds ratio (OR): 8.43; 95% confidence interval (CI): 2.22-32.00], LRRK1 (OR: 100.00; 95% CI: 11.86-843.23) and MEF2A (OR: 32.21; 95% CI: 3.81-272.47). In 15q26 duplication, none of the candidate genes significantly affected tall stature. Using meta-analysis, the present study revealed that IGF1R is not the only key gene responsible for growth abnormalities in 15q26 deletion and duplication syndromes.
Designing the MyoFusion Media: A Serum-Free Medium Optimized for Bovine Satellite Cell Differentiation.
Biotechnol Bioeng
Aysenaz Tavsanli, Viktor Milkevych, Jette Feveile Young +1 more
Cultivated meat production requires efficient differentiation of muscle progenitor cells into myotubes without relying on animal-derived serum, which poses ethical and scalability challenges. This study aimed to develop a chemically defined, serum-free medium optimized for bovine satellite cell differentiation. Using a data-driven design of experiments approach, we systematically screened 13 growth factors and supplements previously associated with myogenesis. Fusion index served as the primary metric for differentiation efficiency, complemented by additional morphological traits. Initial screening identified platelet-derived growth factor BB (PDGF-BB), cytosine arabinoside, and linoleic acid as key contributors, with transforming growth factor beta (TGF-β) included for its biological relevance. Subsequent optimization employed full factorial and central composite designs combined with response surface modeling to refine concentration ranges and evaluate interactions. The resulting formulation, termed MyoFusion, consists of DMEM supplemented with 4.5 × 10⁻⁶ mg/mL TGF-β1, 4.66 × 10⁻⁶ mg/mL PDGF-BB, 0.73 × 10⁻⁵ mg/mL cytosine arabinoside, and 2.07 × 10⁻⁴ mg/mL linoleic acid. Experimental validation demonstrated that MyoFusion achieved a fusion index of 65.08 ± 4.97, representing an improvement of up to 52.7% compared to serum-based controls (2% FBS). Correlation analyses confirmed strong associations between fusion index and other differentiation traits under serum-free conditions, indicating robust myotube formation. These findings establish MyoFusion as a promising serum-free alternative for cultivated meat applications, supporting ethical and scalable production while maintaining differentiation efficiency comparable to or exceeding traditional serum-containing media.
Esophageal Motility Patterns Are Not Impacted By Glucagon-Like Peptide-1 Receptor Agonist Use.
J Clin Gastroenterol
Annie L Wang, Laura Bach, David A Leiman
Glucagon-like peptide-1 receptor agonist (GLP-1RA) use is associated with delayed gastric emptying. It is unknown whether GLP-1RAs affect esophageal motility. We aimed to assess the relationship between GLP-1RA use and esophageal function test results.
Glucagon-like peptide-1 receptor agonists in psoriasis and psoriatic arthritis: emerging evidence and future research opportunities.
Front Immunol
Giovanni Ciancio, Beatrice Maranini, Gilda Sandri +5 more
Psoriasis (PsO) and psoriatic arthritis (PsA) are chronic immune-mediated diseases often associated with obesity, metabolic syndrome, and type 2 diabetes mellitus. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), initially developed for T2DM, exert both metabolic and anti-inflammatory effects, which may offer therapeutic benefits for psoriatic disease, particularly in the early stages of PsA.
Methyl Proton Spin Relaxation (R2/R1) Enables Sensitive Detection of pH-Dependent Oligomerization in GLP-1 Analogs.
Anal Chem
Jiaqi Lu, Eric Pang, Kang Chen
Liquid buffer pH influences the peptide higher order structure (HOS), including oligomerization, with important implications for peptide drug formulation development and stability control. Although dynamic light scattering (DLS) and diffusion-ordered spectroscopy (DOSY) NMR are commonly used to assess particle size (e.g., radius r) through measurement of translational diffusion coefficients (Dt), their sensitivity to subtle pH-dependent oligomerization changes can be limited. Here, using glucagon-like peptide-1 (GLP-1) analogs liraglutide and semaglutide as model peptides, we introduce the methyl proton spin relaxation rate ratio (R2/R1) as a sensitive NMR metric for detecting pH-dependent changes in peptide oligomerization. Diffusion coefficients measured using DLS and DOSY-NMR exhibited an overall increasing trend from pH 6.6 to 8.5, consistent with a shift toward smaller oligomers in basic solution; however, insignificant differences (p value > 0.05) were observed between pH 7.1 and 8.5 for liraglutide and between pH 6.6 and 8.2 for semaglutide. In contrast, the methyl proton R2/R1 decreased significantly with increasing pH, even within the narrow pH range of 7.1-7.7 (p value < 0.05), demonstrating smaller oligomer formation and less exchange at basic pH. The improved sensitivity arises because R2/R1 depends on both rotational diffusion (Dr ∝ r-3) and exchange kinetics, whereas DLS and DOSY depend on Dt (∝ r-1). Consequently, the R2/R1 metric offers enhanced discriminatory power for resolving subtle pH-dependent peptide oligomerization in solution and serves as a practical analytical approach for peptide formulation development and stability control.
Glucagon-Like Peptide-1 Receptor Agonists Inhibit the Initiation of Toxic Amyloid-β42 Aggregation.
J Am Chem Soc
Lucas B Fallot, Carol A Anderson, Johnathan R Pinc +10 more
The aggregation of the 42-residue form of the amyloid-β peptide (Aβ42) is important in Alzheimer's disease (AD). Preclinical and clinical findings support that glucagon-like peptide-1 receptor agonists (GLP-1RAs) can protect against neuroinflammation and neurodegeneration with potential therapeutic relevance for AD, but studies of their direct effects on Aβ42 are limited. Herein, we investigated five FDA-approved GLP-1RAs, and show semaglutide, tirzepatide, and liraglutide inhibit Aβ42 aggregation. Semaglutide and tirzepatide delayed Aβ42 aggregation by targeting the primary nucleation microscopic step, with submicromolar IC50 values for primary nucleation (KIP). Liraglutide was highly effective at suppressing primary nucleation with a very low KIP value, and it demonstrated an additional modest inhibition of secondary nucleation. Consistent with a dominant effect on primary nucleation, Aβ42 formed β-sheet-rich fibrils in the presence of these GLP-1RAs. Aβ42 fibrils formed with semaglutide or tirzepatide had morphological properties and templating efficiencies that were similar to unmodified fibrils, while liraglutide significantly reduced fibril maturity, increased fibril tortuosity and length, and attenuated the ability of fibrils to passively self-replicate whether they were formed in the presence of liraglutide or exposed to this GLP-1RA after their formation. These results provide molecular-level insight into how specific GLP-1RAs can selectively target the fundamental steps governing toxic Aβ42 aggregation. Further studies are warranted to determine if current or next-generation anti-amyloid GLP-1RAs can delay or prevent AD through multifaceted protective mechanisms, including the direct inhibition of Aβ42 aggregation.
Corpora amylacea and glymphatic system in temporal lobe epilepsy patients: Clinicopathological correlation.
Epilepsia
Dalila Biancheri, Laura Rossini, Cinzia Cagnoli +12 more
Corpora amylacea (CA), now called wasteosomes, are basophilic inclusions associated with aging, neurodegeneration, and impaired glymphatic waste clearance. Their presence is well described in temporal lobe epilepsy with hippocampal sclerosis (TLE-HS) and related to hippocampal neuronal loss and longer epilepsy duration. Here, we assessed CA deposition in TLE patients submitted to epilepsy surgery with any histological diagnosis and explored its relationship with clinical and neuropsychological variables. Histological signs of the glymphatic system were evaluated.
Health-related quality of life domains relevant to people in Europe undergoing cancer treatment: a systematic review of qualitative research.
Qual Life Res
Catalina Lizano-Barrantes, Clara Amat-Fernandez, Olatz Garin +76 more
To identify and synthesize evidence from European qualitative studies on cancer-related quality of life outcomes, needs, experiences, preferences, and concerns of people undergoing cancer treatment in the last decade.
Superoxide dismutase in intervertebral disc degeneration: from pathophysiological mechanism to therapeutic strategies.
Mol Biol Rep
Huan Liu, Fengguang Yang, Guangzhi Zhang +4 more
Reactive oxygen species (ROS) induce inflammation, senescence and various forms of cell death in nucleus pulposus cells. By promoting these reactions and their interplay, ROS significantly accelerate intervertebral disc degeneration (IDD). Conventional surgical interventions and analgesics can alleviate symptoms but fail to halt the disease progression mechanistically. Eliminating ROS may serve as a fundamental therapeutic approach to mitigate IDD. Within the endogenous antioxidant defense system for scavenging ROS, superoxide dismutase (SOD) serves as the first line of defense, playing an irreplaceable role in initiating the clearance of reactive species. Furthermore, transcriptomics and single-cell sequencing analyses have identified SOD as a key gene in nucleus pulposus tissue degeneration, underscoring its unique value in the research of antioxidant therapies for IDD. Recently, a range of SOD-centered therapeutic strategies, including the enhancement of endogenous SOD via drugs, hormones, herbal medicines, exosomes, genetically engineered stem cells, in addition to the use of exogenous SOD nanozymes have been explored. Despite these advancements, a comprehensive overview of these emerging approaches remains elusive. This review details how ROS contribute to IDD and critically assesses current and future SOD-centered therapeutic strategies, providing valuable insights for clinical practice and research directions.
Oat β-glucan reshapes gut microbiota to enhance glucose homeostasis via coordinated modulation of bile acid conjugation and succinate-dependent intestinal gluconeogenesis.
Food Chem
Yantong Meng, Siqi Li, Keyi Zhou +4 more
Dietary fibers-induced gut microbiota changes influence diabetes through bile acid metabolism. Oat β-glucan is a beneficial dietary fiber that improves glucose metabolism, but its mechanism of regulating gut microbiota-mediated bile acid metabolism and exerting hypoglycemic effects remains unclear. Here, we found that oat β-glucan improved glucose intolerance and insulin resistance and promoted glucagon-like peptide-1 (GLP-1) secretion in obese mice. The enhanced production of secondary bile acids such as lithocholic acid (LCA) and deoxycholic acid (DCA), which were associated with the enriched Faecalibaculum, norank_f_Muribaculaceae, Bifidobacterium and Akkermansia induced by oat β-glucan, were proven to promote GLP-1 secretion via inhibiting FXR. Simultaneously, succinic acid, which was elevated in fecal metabolites by oat β-glucan, was linked to enhanced intestinal gluconeogenesis and contributed to GLP-1 secretion. Overall, oat β-glucan modulated gut microbiota to increase secondary bile acids and succinic acid, thereby stimulating GLP-1 secretion to promote glucose metabolism in mice fed a Western diet.
Combination amino acids and glucose effects on insulin and GLP-1 secretion.
Biochem J
Kenneth H C Koh, Junhe Zhao, Sarah X Luo +3 more
Dietary nutrients such as amino acids possess an insulinogenic effect. However, not all amino acids were meticulously investigated for their effect on both insulin and incretin secretion, and the effect of amino acids given in different combinations remained incompletely characterized. In the present work, we reported the quantitative effect of individual and combinatorial amino acids in conjunction with low and high glucose, respectively, on insulin secretion from human islets and on glucagon-like peptide-1 (GLP-1) secretion from secretin tumor cell (STC-1). STC-1 cells were incubated with amino acid treatment solutions individually and in combinations at low and high glucose to investigate GLP-1 secretion. Batches of 15 islets were sequentially treated with 3 mM glucose, combinatorial amino acid treatment solutions at low and high glucose, and finally 25 mM KCl to quantify insulin secretion. Lysine, threonine, tryptophan, phenylalanine, and aspartic acid significantly increased GLP-1 secretion in STC-1 cells compared with negative control. Branched-chain amino acids (BCAAs) stimulated greater GLP-1 secretion only at high glucose and significantly induce insulin secretion in islets even in low glucose. Other amino acid combinations tested were able to augment GLP-1 secretion even in the absence of glucose but failed to further stimulate insulin secretion in human islets when given concurrently at higher glucose concentrations. In conclusion, the findings from our work could be used to infer the expected insulinogenic effect and glycemic response for proteins with different amino acid compositions.
Direct or Indirect Action? Mechanisms of the Antiatherosclerotic Effects of Glucagon-Like Peptide-1 Receptor Agonists.
Cardiovasc Ther
Michał Zawadzki, Monika Karczewska-Kupczewska
Cardiovascular diseases (CVD) remain the leading cause of global mortality. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) significantly reduce major adverse cardiovascular events in patients with and without Type 2 diabetes, offering benefits that extend beyond glycemic control. This review summarizes proposed multifactorial mechanisms underlying these effects, categorizing them into indirect and direct pathways. Indirect mechanisms include, among others, improvements in lipid metabolism, insulin sensitivity, blood pressure, and renal protection. In addition to the previously described effects, GLP-1 RAs may exert direct vascular actions, including anti-inflammatory actions, suppression of oxidative stress, improved endothelial function, modulation of macrophage polarization, reduction of adhesion molecule expression, and inhibition of vascular smooth muscle cell proliferation and migration, as well as downregulation of matrix metalloproteinases and plasminogen activator inhibitor-1. Collectively, these processes contribute to plaque stabilization and reduced atherothrombotic risk. Although clinical evidence for cardiovascular risk reduction of GLP-1 RAs is robust, mechanistic insights are predominantly derived from preclinical or animal models. Therefore, further functional studies in humans are warranted to clarify the direct antiatherogenic actions of GLP-1 RAs.
GLP-1 Receptor Agonist Associated Unmasking of Insulinoma.
Eur J Case Rep Intern Med
Eden Simonov, Rina Berger, Olga Shishkina +2 more
Insulinoma is a rare functional pancreatic neuroendocrine tumour and the most common cause of endogenous hyperinsulinaemic hypoglycaemia in adults. Diagnosis is frequently delayed due to non-specific and intermittent symptoms, and a high index of suspicion is needed.
Glucagon-like peptide 1 receptor agonists: anti-inflammatory effects in cardiovascular diseases.
Can J Physiol Pharmacol
Zorislava Bajic, Tanja Sobot, Miloš P Stojiljković +2 more
The potential therapeutic applications of glucagon-like peptide-1 (GLP-1) have led to the development of GLP-1 receptor agonists (GLP-1RAs), which replicate GLP-1's effects. The primary use of GLP-1RAs is the management of type 2 diabetes (T2DM) by stimulation of insulin secretion. In addition to its metabolic functions, GLP-1 exhibits significant anti-inflammatory effects through various molecular pathways, utilizing both direct and indirect mechanisms. Experimental studies have revealed that GLP-1RAs modulate multiple inflammatory pathways, including cytokine production, oxidative stress, glucotoxicity, lipotoxicity, and immune cell recruitment across multiple organs. They interact with their receptors on immune cells, thereby reducing the production of inflammatory cytokines and decreasing the infiltration of immune cells into tissues. There is considerable overlap among the pathways activated by GLP-1R in cardiovascular tissue, which can lead to anti-apoptotic, antioxidative, and anti-inflammatory effects. Clinical studies have confirmed the anti-inflammatory effects of GLP-1RAs in conditions such as acute myocardial infarction, left ventricular dysfunction, coronary artery disease, and ST-segment elevation myocardial infarction. Notably, GLP-1RAs are included in the European Society of Cardiology guidelines for managing cardiovascular disease in patients with T2DM.
[Efficacy of the 3-month formulation of triptoreli in children with idiopathic central precocious puberty].
Zhongguo Dang Dai Er Ke Za Zhi
Kang Yu, Yu-Hang Bei, Shuang-Lin-Zi Deng +1 more
To evaluate the clinical efficacy and safety of the 3-month formulation of triptorelin (triptorelin pamoate) in the treatment of idiopathic central precocious puberty (ICPP) in children.
Transcriptomic and Molecular Insights into the Response of Multidrug-Resistant Helicobacter pylori to Human Neutrophil Peptide 1 (HNP-1).
Probiotics Antimicrob Proteins
Zarith Nameyrra Md Nesran, Alfizah Hanafiah, Asif Sukri +3 more
Multidrug-resistant (MDR) H. pylori infections present significant challenges in treatment, driving the need for novel therapeutic agents. Human neutrophil peptide 1 (HNP-1), an antimicrobial peptide, has shown potential activity against antibiotic-resistant pathogens, yet its specific efficacy and mechanisms against MDR H. pylori remain unexplored. The objective of this study was to evaluate the antibacterial activity of HNP-1 against multidrug-resistant (MDR) H. pylori. This study investigated the effects of HNP-1 on MDR H. pylori through a combination of in vitro and in silico approaches, including minimum inhibitory concentration (MIC) assays, molecular docking, and RNA sequencing. The MIC assay revealed that H. pylori strains exhibited high resistance to HNP-1 at 512 μg/mL, highlighting the need to understand this interaction at a molecular level. Molecular docking analysis identified key protein targets, RdxA, 23S rRNA, GyrA, and GyrB with varying binding affinities to HNP-1, suggesting potential pathways impacted by the peptide. RNA sequencing further revealed significant transcriptomic changes, with the ribosomal pathway and other metabolic pathways significantly upregulated upon treatment with HNP-1. These findings provide insights into H. pylori's adaptive responses to HNP-1, enhance our understanding of its interactions with MDR H. pylori strains, and highlight pathways that may serve as future therapeutic targets, underscoring the need for continued research into AMPs as complementary therapeutic strategies.
Development of specific ELISAs for luteinizing hormone and follicle-stimulating hormone in the commercially important cyprinid fish.
Gen Comp Endocrinol
Jiying Chen, Yu Ouyang, Xiangtong Zeng +9 more
Grass carp (Ctenopharyngodon idella) is an important aquaculture species, yet no specific immunoassay is available for quantifying its pituitary gonadotropins-luteinizing hormone (LH) and follicle-stimulating hormone (FSH)-which are key regulators of reproduction in vertebrates. Here, we developed and validated competitive enzyme-linked immunosorbent assays (ELISAs) for grass carp LH and FSH using recombinant proteins and specific polyclonal antibodies. The recombinant proteins were expressed in E. coli based on the native hormone sequences, and polyclonal antibodies were generated in rabbits. Antibody specificity was validated by immunohistochemistry and western blotting, which confirmed that LH and FSH are produced by distinct cell populations in the grass carp pituitary, consistent with the organizational pattern observed in other teleosts. The standard curves showed excellent correlation (mean R2 = 0.994). Assay sensitivities were 1.27 ng/mL for LH and 1.18 ng/mL for FSH, with IC50 values of 9.19 ng/mL and 9.29 ng/mL, respectively. Intra-assay CVs ranged from 0.68% to 4.10% (LH) and 0.44% to 4.27% (FSH), while inter-assay CVs averaged 5.43% and 1.92%, demonstrating good reproducibility. Using this assay, we quantified LH and FSH levels in grass carp across different developmental stages, revealing distinct age- and sex-specific secretion patterns that provide insights into the differential regulation of gonadotropins during sexual maturation in cyprinids. The assay also successfully detected hormone responses to salmon gonadotropin-releasing hormone (sGnRH) stimulation both in vivo and in vitro. This ELISA system provides a reliable tool for investigating gonadotropin dynamics in grass carp and offers a methodological foundation for comparative studies on the endocrine regulation of reproduction in teleost fishes.
The dynamic adrenal response of children to cardiac surgery and cardiac catheterisation.
J Clin Endocrinol Metab
Daniel Paul Fudulu, Isabella Marinelli, Daniel Galvis +22 more
The hypothalamic-pituitary-adrenal (HPA) axis is the key homeostatic system regulating the response to surgical stress. Imbalances in HPA axis hormones increase morbidity and mortality in children after cardiac surgery. Despite this, the physiology of the HPA axis in children undergoing cardiac surgery is poorly understood, leading to controversies in clinical practice.
Endothelium-Dependent Nitric Oxide-Mediated Vasorelaxant Effects of BPC 157 in Human Internal Mammary Artery.
J Clin Med
Alperen Kutay Yildirim, Ahmet Onur Dastan, Meric Demeli Ertus +3 more
Background/Objectives: Body Protection Compound-157 (BPC 157) is a stable gastric pentadecapeptide with cytoprotective, pro-angiogenic, and nitric oxide (NO)-modulating properties that has gained increasing attention for its therapeutic potential. Although vasodilatory effects have been demonstrated in animal models, functional evidence in human arterial tissue remains limited. This study investigated the effects of BPC 157 on vascular tone in human internal mammary artery (IMA) rings and evaluated the contribution of endothelial NO signaling. Methods: Residual IMA segments obtained from elective coronary artery bypass graft surgeries (n = 12) were dissected into endothelium-intact and endothelium-denuded rings. Following equilibration, the rings were challenged by phenylephrine (PheE; 3 × 10-6 M) to induce contraction. Cumulative concentration-response curves of BPC 157 (0.01-1 mg/mL) for five consecutive doses were constructed. The involvement of NO was assessed by BPC 157 dose-response curves in the nitric oxide synthase (NOS) inhibitor Nω-nitro-L-arginine methyl ester (L-NAME; 10-6 M) pre-incubated rings. Maximum force of contraction, area under the curve, maximum response (Emax), and negative logarithm of the half-maximal effective concentration (pEC50) values were analyzed. Results: BPC 157 produced a concentration-dependent reduction in PheE-induced contraction in both groups, with significantly greater relaxation in endothelium-intact rings (p < 0.05). L-NAME increased contractile responsiveness in intact rings and attenuated BPC 157-induced relaxation. Under NOS inhibition, differences between groups progressively diminished and concentration-response curves converged at higher concentrations. Emax analysis demonstrated that endothelial integrity markedly enhanced maximal vasorelaxation, whereas this advantage was largely abolished after NOS inhibition. Conclusions: BPC 157 induces concentration-dependent vasorelaxation in human arterial tissue, predominantly mediated via an endothelium-dependent NO pathway. Endothelial integrity primarily enhances maximal efficacy, while residual effects indicate additional mechanisms. These findings provide early mechanistic evidence for the vascular activity of BPC 157, although further molecular and in vivo studies are required to clarify its clinical relevance.
Therapeutic Peptides in Aesthetic, Metabolic and Endocrine Conditions: Effects, Safety, Clinical Applications, and Future Perspectives.
Int J Mol Sci
Guilherme Renke, Lucas Chinellato
Therapeutic peptides are short chains of amino acids used to treat metabolic and endocrine conditions such as obesity and type 2 diabetes. While several peptide drugs have undergone rigorous approval processes that evaluate both safety and efficacy, novel, unapproved compounds have emerged and are rapidly expanding into preventive medicine and performance enhancement. Our objective is to present the effects, clinical applications, safety profiles, and regulatory status of prominent peptides used to treat several conditions. We reviewed 106 articles, prioritizing systematic reviews, meta-analyses, and randomized controlled trials in the PubMed, ScienceDirect, and SciELO databases. Our results suggest that therapeutic peptides are a promising tool for treating type 2 diabetes and obesity, for skin rejuvenation, and as hormone analogs for specific diseases and conditions. Although these are strategic and innovative options that can improve health, performance, and longevity, further studies are needed before most new peptides can be used safely in humans.