Pub Date : 2025-09-13DOI: 10.1016/j.peptides.2025.171439
Zina Bai , Zelin Chen , Tongxinwei Sun , Cuiqing Ma , Aihong Meng
Irisin, initially described as a myokine, is widely distributed throughout the body and is released during physical exercise. It exerts beneficial effects on multiple tissues and, organs, and in systemic diseases, including neurological, metabolic, cardiovascular, pulmonary, and musculoskeletal disorders. Recent studies have highlighted the role of irisin receptors in various disease models and cell types, identifying integrin αV, particularly integrin αVβ5, as a key irisin-binding receptor. This review summarizes the current findings on irisin receptor biology and elucidates the mechanisms by which irisin mediates its effects via these receptors in various diseases. We propose that integrin αVβ5 receptors may represent promising therapeutic target for the treatment of diseases associated with exercise-induced irisin, offering a novel perspective for the alleviation of systemic diseases through exercise and rehabilitation.
{"title":"Potential role of integrin αV as irisin receptor and advances in research","authors":"Zina Bai , Zelin Chen , Tongxinwei Sun , Cuiqing Ma , Aihong Meng","doi":"10.1016/j.peptides.2025.171439","DOIUrl":"10.1016/j.peptides.2025.171439","url":null,"abstract":"<div><div>Irisin, initially described as a myokine, is widely distributed throughout the body and is released during physical exercise. It exerts beneficial effects on multiple tissues and, organs, and in systemic diseases, including neurological, metabolic, cardiovascular, pulmonary, and musculoskeletal disorders. Recent studies have highlighted the role of irisin receptors in various disease models and cell types, identifying integrin αV, particularly integrin αVβ5, as a key irisin-binding receptor. This review summarizes the current findings on irisin receptor biology and elucidates the mechanisms by which irisin mediates its effects via these receptors in various diseases. We propose that integrin αVβ5 receptors may represent promising therapeutic target for the treatment of diseases associated with exercise-induced irisin, offering a novel perspective for the alleviation of systemic diseases through exercise and rehabilitation.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"193 ","pages":"Article 171439"},"PeriodicalIF":2.9,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145070169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-12DOI: 10.1016/j.peptides.2025.171440
Nathalie van Walraven , Richard J. FitzGerald , Hans-Jürgen Danneel , Miryam Amigo-Benavent
Bioactive peptides are increasingly employed in cosmetic products and these are generically known as cosmetic peptides. This review aims to provide an update on current information related to commercially available cosmetic peptides, and the in vitro and ex vivo evidence for their potential biological effects. A total of 102 commercially available cosmetic peptides were identified. The majority of these peptides are inspired by molecules already found in the human body, including sequences from extracellular matrix molecules, also known as matrikines. Cosmetic peptides are produced either through chemical synthesis or via biotechnological processes. Their claimed biological activities include signaling to increase collagen and hyaluronic acid production, modulation of pigmentation, maintenance of a healthy skin microbiome, antioxidant activity and cellular defense, immunomodulation, neurotransmitter inhibition, enzyme activity inhibition and trace mineral carriers. The primary structure and current scientific evidence for the bioactivities of these peptides are presented and discussed. The review highlights the diverse methodological approaches used and the outcomes measured in the assessment of cosmetic peptide efficacy. Overall, a large range of cosmetic peptides are commercially available whose efficacy is supported by divergent levels of in vitro and ex vivo data.
{"title":"Bioactive peptides in cosmetic formulations: Review of current in vitro and ex vivo evidence","authors":"Nathalie van Walraven , Richard J. FitzGerald , Hans-Jürgen Danneel , Miryam Amigo-Benavent","doi":"10.1016/j.peptides.2025.171440","DOIUrl":"10.1016/j.peptides.2025.171440","url":null,"abstract":"<div><div>Bioactive peptides are increasingly employed in cosmetic products and these are generically known as cosmetic peptides. This review aims to provide an update on current information related to commercially available cosmetic peptides, and the <em>in vitro</em> and <em>ex vivo</em> evidence for their potential biological effects. A total of 102 commercially available cosmetic peptides were identified. The majority of these peptides are inspired by molecules already found in the human body, including sequences from extracellular matrix molecules, also known as matrikines. Cosmetic peptides are produced either through chemical synthesis or via biotechnological processes. Their claimed biological activities include signaling to increase collagen and hyaluronic acid production, modulation of pigmentation, maintenance of a healthy skin microbiome, antioxidant activity and cellular defense, immunomodulation, neurotransmitter inhibition, enzyme activity inhibition and trace mineral carriers. The primary structure and current scientific evidence for the bioactivities of these peptides are presented and discussed. The review highlights the diverse methodological approaches used and the outcomes measured in the assessment of cosmetic peptide efficacy. Overall, a large range of cosmetic peptides are commercially available whose efficacy is supported by divergent levels of <em>in vitro</em> and <em>ex vivo</em> data.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"193 ","pages":"Article 171440"},"PeriodicalIF":2.9,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145065366","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-19DOI: 10.1016/j.peptides.2025.171438
Tong Ding , Pengjie Zhang , Kunying Wang , Peng Du , Bin Duan
Renal ischemia-reperfusion injury can lead to severe renal function impairment, manifested by a significant increase in serum creatinine, renal tubular obstruction, and even necrosis, which can lead to acute renal failure. This injury can also trigger systemic inflammatory response syndrome and even lead to multiple organ dysfunction. It poses a serious threat to the life and health of patients, so it is urgent to find potential drugs for treatment. In our current work, we evaluated the effects of FGFs on kidney injury caused by ischemia-reperfusion. We first established a model of kidney cell injury caused by ischemia-reperfusion. The biological functions of FGFs were further evaluated through a series of biochemical techniques. The experimental data showed that, FGFs can effectively improve the damage of kidney cells caused by ischemia-reperfusion. FGFs can alleviate iron death and pyroptosis of kidney cells caused by ischemia-reperfusion. Further work showed that FGF4 also alleviated inflammation and oxidative stress damage caused by ischemia-reperfusion. Mechanism research also showed that FGFs effectively alleviated ischemia-reperfusion-induced kidney injury by activating AMPK-mediated signaling pathways. Furthermore, in vivo, we also found that FGF4 can effectively alleviate the kidney ischemia-reperfusion injury. This finding not only indicates the potential therapeutic prospects of FGF4 for ischemic diseases, but also provides a new pharmacological target for the treatment of renal ischemia-reperfusion injury.
{"title":"FGF4 alleviates renal injury caused by ischemia-reperfusion(I/R) by inhibiting ferroptosis and pyroptosis","authors":"Tong Ding , Pengjie Zhang , Kunying Wang , Peng Du , Bin Duan","doi":"10.1016/j.peptides.2025.171438","DOIUrl":"10.1016/j.peptides.2025.171438","url":null,"abstract":"<div><div>Renal ischemia-reperfusion injury can lead to severe renal function impairment, manifested by a significant increase in serum creatinine, renal tubular obstruction, and even necrosis, which can lead to acute renal failure. This injury can also trigger systemic inflammatory response syndrome and even lead to multiple organ dysfunction. It poses a serious threat to the life and health of patients, so it is urgent to find potential drugs for treatment. In our current work, we evaluated the effects of FGFs on kidney injury caused by ischemia-reperfusion. We first established a model of kidney cell injury caused by ischemia-reperfusion. The biological functions of FGFs were further evaluated through a series of biochemical techniques. The experimental data showed that, FGFs can effectively improve the damage of kidney cells caused by ischemia-reperfusion. FGFs can alleviate iron death and pyroptosis of kidney cells caused by ischemia-reperfusion. Further work showed that FGF4 also alleviated inflammation and oxidative stress damage caused by ischemia-reperfusion. Mechanism research also showed that FGFs effectively alleviated ischemia-reperfusion-induced kidney injury by activating AMPK-mediated signaling pathways. Furthermore, in vivo, we also found that FGF4 can effectively alleviate the kidney ischemia-reperfusion injury. This finding not only indicates the potential therapeutic prospects of FGF4 for ischemic diseases, but also provides a new pharmacological target for the treatment of renal ischemia-reperfusion injury.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"192 ","pages":"Article 171438"},"PeriodicalIF":2.9,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144895137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Previous studies have shown that natriuretic peptides (NPs) respond to hypoxia. Mixed venous oxygen saturation (SvO₂) reflects the oxygen balance and may indicate pulmonary hypoxia. In this study, we investigated whether NPs are influenced by SvO₂ and whether this effect differs between A-type natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) in heart failure patients, using structural equation modeling (SEM). We examined 179 patients with pre-heart failure/heart failure who underwent Swan-Ganz catheterization, and investigated the relationship between NP levels and various clinical parameters, including SvO₂. The path model showed that pulmonary artery wedge pressure (PAWP) and administration of angiotensin receptor-neprilysin inhibitor (ARNI) were significantly positively associated with ANP (PAWP: standardized regression coefficient [St. β] =0.281, P = 0.002; ARNI administration: St. β=0.396, P < 0.001). PAWP and ischemic heart disease (IHD) were positively associated with BNP, whereas the estimated glomerular filtration rate (eGFR) and SvO₂ were negatively associated with BNP (PAWP: St. β =0.370, P < 0.001; IHD: St. β =0.241, P < 0.001; eGFR: St. β =-0.209, P = 0.003; SvO₂: St. β =-0.528, P < 0.001). ANP was not associated with arterial oxygen saturation (SaO₂) or SvO₂, whereas BNP showed a negative relationship with SvO₂ but was not associated with SaO₂. Thus, an increased BNP, but not ANP, correlates strongly with decreased SvO₂, an indicator of hypoxia before pulmonary circulation, independent of hemodynamic indices.
先前的研究表明，利钠肽（NPs）对缺氧有反应。混合静脉氧饱和度（SvO₂）反映氧平衡，可能提示肺缺氧。在本研究中，我们利用结构方程模型（SEM）研究了心力衰竭患者的NPs是否受到SvO₂的影响，以及这种影响在a型利钠肽（ANP）和b型利钠肽（BNP）之间是否存在差异。我们检查了179例接受Swan-Ganz导管置入的心衰前期/心衰患者，并研究了NP水平与包括SvO₂在内的各种临床参数的关系。路径模型显示肺动脉楔压（PAWP）和血管紧张素受体-neprilysin抑制剂（ARNI）给药与ANP呈显著正相关(PAWP：标准化回归系数[St. β] =0.281， P=0.002；ARNI给药：St. β=0.396， P
{"title":"Correlation Between decreased mixed venous oxygen saturation and increased B-type natriuretic peptides independent of hemodynamics in pre-heart failure/heart failure patients","authors":"Yusuke Kashiwagi , Tomohisa Nagoshi , Ryuji Funaki , Yuto Mashitani , Satoshi Ito , Kazuo Ogawa , Makoto Kawai , Michifumi Tokuda , Michihiro Yoshimura","doi":"10.1016/j.peptides.2025.171433","DOIUrl":"10.1016/j.peptides.2025.171433","url":null,"abstract":"<div><div>Previous studies have shown that natriuretic peptides (NPs) respond to hypoxia. Mixed venous oxygen saturation (SvO₂) reflects the oxygen balance and may indicate pulmonary hypoxia. In this study, we investigated whether NPs are influenced by SvO₂ and whether this effect differs between A-type natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) in heart failure patients, using structural equation modeling (SEM). We examined 179 patients with pre-heart failure/heart failure who underwent Swan-Ganz catheterization, and investigated the relationship between NP levels and various clinical parameters, including SvO₂. The path model showed that pulmonary artery wedge pressure (PAWP) and administration of angiotensin receptor-neprilysin inhibitor (ARNI) were significantly positively associated with ANP (PAWP: standardized regression coefficient [St. β] =0.281, P = 0.002; ARNI administration: St. β=0.396, P < 0.001). PAWP and ischemic heart disease (IHD) were positively associated with BNP, whereas the estimated glomerular filtration rate (eGFR) and SvO₂ were negatively associated with BNP (PAWP: St. β =0.370, P < 0.001; IHD: St. β =0.241, P < 0.001; eGFR: St. β =-0.209, P = 0.003; SvO₂: St. β =-0.528, P < 0.001). ANP was not associated with arterial oxygen saturation (SaO₂) or SvO₂, whereas BNP showed a negative relationship with SvO₂ but was not associated with SaO₂. Thus, an increased BNP, but not ANP, correlates strongly with decreased SvO₂, an indicator of hypoxia before pulmonary circulation, independent of hemodynamic indices.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"192 ","pages":"Article 171433"},"PeriodicalIF":2.8,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144708415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-07-22DOI: 10.1016/j.peptides.2025.171434
Ming-Jie Yuan , Peng Zhong , Zhi-Xuan Shu , Li-Hua Zheng , Tao Liu , Song Dang
Background
Therapeutic angiogenesis has demonstrated efficacy in revascularizing ischemic heart tissue and reducing the progression of cardiac remodeling following myocardial infarction. Recent studies have highlighted the significance of the glycolytic process in maintaining endothelial cell function and cardiac homeostasis. However, the specific role of glycolysis in angiogenesis post-myocardial infarction remains poorly understood. This study aims to explore whether ghrelin/GHSR-1a promotes angiogenesis after myocardial infarction through glycolysis.
Methods and results
Myocardial infarction was induced in mice, and our experiments showed that GHSR-1a overexpression led to a significant increase in the density of α-SMA-positive vessels in the peri-infarct zones, compared to the MI group, at day 7 post-infarction. Furthermore, elevated FGF-21 levels were observed in the border zone of the infarcted area seven days post-acute myocardial infarction. We also identified a modified GHSR-1a/FGF-21 axis in cardiac endothelial cells, where GHSR-1a knockdown reduced the expression of both FGF-21 and AMPK. In vitro, ghrelin enhanced glycolytic activity by increasing the expression of glycolytic enzymes. Moreover, ghrelin significantly stimulated endothelial tube formation and enhanced cell viability; however, these effects were attenuated following FGF-21 knockdown.
Conclusion
Our findings demonstrate that ghrelin/GHSR-1a improves neovascularization and enhances glycolysis in cardiac endothelial cells by modulating FGF-21. These results lay the groundwork for further experimental and clinical investigations to explore pharmaceutical approaches for treating ischemic heart disease.
{"title":"Ghrelin/GHSR-1a promotes angiogenesis after myocardial infarction through the glycolytic process","authors":"Ming-Jie Yuan , Peng Zhong , Zhi-Xuan Shu , Li-Hua Zheng , Tao Liu , Song Dang","doi":"10.1016/j.peptides.2025.171434","DOIUrl":"10.1016/j.peptides.2025.171434","url":null,"abstract":"<div><h3>Background</h3><div>Therapeutic angiogenesis has demonstrated efficacy in revascularizing ischemic heart tissue and reducing the progression of cardiac remodeling following myocardial infarction. Recent studies have highlighted the significance of the glycolytic process in maintaining endothelial cell function and cardiac homeostasis. However, the specific role of glycolysis in angiogenesis post-myocardial infarction remains poorly understood. This study aims to explore whether ghrelin/GHSR-1a promotes angiogenesis after myocardial infarction through glycolysis.</div></div><div><h3>Methods and results</h3><div>Myocardial infarction was induced in mice, and our experiments showed that GHSR-1a overexpression led to a significant increase in the density of α-SMA-positive vessels in the peri-infarct zones, compared to the MI group, at day 7 post-infarction. Furthermore, elevated FGF-21 levels were observed in the border zone of the infarcted area seven days post-acute myocardial infarction. We also identified a modified GHSR-1a/FGF-21 axis in cardiac endothelial cells, where GHSR-1a knockdown reduced the expression of both FGF-21 and AMPK. In vitro, ghrelin enhanced glycolytic activity by increasing the expression of glycolytic enzymes. Moreover, ghrelin significantly stimulated endothelial tube formation and enhanced cell viability; however, these effects were attenuated following FGF-21 knockdown.</div></div><div><h3>Conclusion</h3><div>Our findings demonstrate that ghrelin/GHSR-1a improves neovascularization and enhances glycolysis in cardiac endothelial cells by modulating FGF-21. These results lay the groundwork for further experimental and clinical investigations to explore pharmaceutical approaches for treating ischemic heart disease.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"192 ","pages":"Article 171434"},"PeriodicalIF":2.8,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144702115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-07-16DOI: 10.1016/j.peptides.2025.171429
Xuepin Chen , Tianying Wang , Yan Gao , Guo an Wang , Jun Guan , Hongyan Dai
Recent research indicates that inhibiting myocardial ferroptosis may help alleviate diabetic cardiomyopathy (DCM). Liraglutide (LIRA), a glucagon-like peptide-1 receptor agonist, has been shown to offer cardiovascular protective effects. Nevertheless, the specific role of LIRA and its relationship with myocardial ferroptosis in type 2 DCM is still not well understood. An in vivo model of type 2 diabetes mellitus (T2DM) was created using spontaneous diabetes Goto-Kakizaki (GK) rats. These rats received LIRA at a dose of 200 μg/kg/day through daily subcutaneous injections for 8 weeks. In vitro experiments involved treating H9C2 cells with different concentrations of glucose, LIRA, siRNA-Nrf2, Fer-1, or their combinations. The results demonstrated that LIRA enhanced glucose metabolism, improved cardiac remodeling and function, reduced lipid peroxidation, and mitigated myocardial ferroptosis in diabetic rats. Additionally, LIRA was found to increase the levels of proteins associated with ferroptosis, such as Cyto-NRF2, Nu-NRF2, PTGS2, FTH-1, and GPX4 in DCM. In vitro, high glucose levels intensified the production of lipid reactive oxygen species (ROS) and lipid peroxidation, diminished mitochondrial mass, and lowered the levels of ferroptosis-related proteins, ultimately triggering ferroptosis. Notably, these detrimental effects were mitigated by LIRA treatment. Overall, these results indicate that LIRA may serve as a valuable therapeutic option for addressing myocardial ferroptosis by promoting NRF2 expression in type 2 DCM.
{"title":"Liraglutide suppresses ferroptosis by upregulation NRF2 in type 2 diabetic cardiomyopathy","authors":"Xuepin Chen , Tianying Wang , Yan Gao , Guo an Wang , Jun Guan , Hongyan Dai","doi":"10.1016/j.peptides.2025.171429","DOIUrl":"10.1016/j.peptides.2025.171429","url":null,"abstract":"<div><div>Recent research indicates that inhibiting myocardial ferroptosis may help alleviate diabetic cardiomyopathy (DCM). Liraglutide (LIRA), a glucagon-like peptide-1 receptor agonist, has been shown to offer cardiovascular protective effects. Nevertheless, the specific role of LIRA and its relationship with myocardial ferroptosis in type 2 DCM is still not well understood. An <em>in vivo</em> model of type 2 diabetes mellitus (T2DM) was created using spontaneous diabetes Goto-Kakizaki (GK) rats. These rats received LIRA at a dose of 200 μg/kg/day through daily subcutaneous injections for 8 weeks. <em>In vitro</em> experiments involved treating H9C2 cells with different concentrations of glucose, LIRA, siRNA-Nrf2, Fer-1, or their combinations. The results demonstrated that LIRA enhanced glucose metabolism, improved cardiac remodeling and function, reduced lipid peroxidation, and mitigated myocardial ferroptosis in diabetic rats. Additionally, LIRA was found to increase the levels of proteins associated with ferroptosis, such as Cyto-NRF2, Nu-NRF2, PTGS2, FTH-1, and GPX4 in DCM. <em>In vitro</em>, high glucose levels intensified the production of lipid reactive oxygen species (ROS) and lipid peroxidation, diminished mitochondrial mass, and lowered the levels of ferroptosis-related proteins, ultimately triggering ferroptosis. Notably, these detrimental effects were mitigated by LIRA treatment. Overall, these results indicate that LIRA may serve as a valuable therapeutic option for addressing myocardial ferroptosis by promoting NRF2 expression in type 2 DCM.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"192 ","pages":"Article 171429"},"PeriodicalIF":2.8,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144656018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Diabetes mellitus (DM) is a chronic metabolic disease considered the “epidemic” of the new millennium, with devastating impacts on quality of life and global prevalence. One of the most common ocular complications is diabetic keratopathy (DK), often overlooked compared to other diabetes-related diseases. This disease causes significant corneal damage and is characterized by an overactive inflammatory condition, alteration of the corneal epithelial barrier, and delayed wound healing. Current therapies do not always ensure effective restoration of corneal function. In our previous study, we found that changes in the endogenous pituitary adenylate cyclase-activating polypeptide (PACAP) expression can concur for delayed epithelial wound healing in diabetic cornea. Moreover, the peptide showed cytoprotective effects on the corneal epithelium, promoting cell viability and wound healing under high glucose conditions, suggesting its potential effect in this diabetes-related disease. Therefore, this study aims to investigate the effect of PACAP against hyperglycemia-induced inflammation. To better resemble the natural conditions of corneal epithelium in vivo, an air-liquid interface (ALI) culture of the corneal epithelial cells was performed. The ALI corneal epithelium was cultured under high-glucose conditions to generate a model of DK. Our model reproduced well-established molecular and cellular characteristics of this pathology, including barrier thickness decrease and inflammation, with increased expression of IL-1β, TNF-α, and p-NF-kB. Our results indicated that PACAP significantly reduced the levels of proinflammatory cytokines IL-1β and TNF-α and inhibited the activation of NF-kB, an important mediator of inflammation. Moreover, PACAP improved epithelial morphology and corneal barrier thickness, suggesting its therapeutic potential in the treatment of DK.
{"title":"Protective effects of PACAP against high glucose-induced inflammation on air-liquid interface corneal epithelium barrier","authors":"Grazia Maugeri , Agata Grazia D’Amico , Nicoletta Palmeri , Elisabetta Pricoco , Desiree Brancato , Concetta Federico , Velia D’Agata","doi":"10.1016/j.peptides.2025.171432","DOIUrl":"10.1016/j.peptides.2025.171432","url":null,"abstract":"<div><div>Diabetes mellitus (DM) is a chronic metabolic disease considered the “epidemic” of the new millennium, with devastating impacts on quality of life and global prevalence. One of the most common ocular complications is diabetic keratopathy (DK), often overlooked compared to other diabetes-related diseases. This disease causes significant corneal damage and is characterized by an overactive inflammatory condition, alteration of the corneal epithelial barrier, and delayed wound healing. Current therapies do not always ensure effective restoration of corneal function. In our previous study, we found that changes in the endogenous pituitary adenylate cyclase-activating polypeptide (PACAP) expression can concur for delayed epithelial wound healing in diabetic cornea. Moreover, the peptide showed cytoprotective effects on the corneal epithelium, promoting cell viability and wound healing under high glucose conditions, suggesting its potential effect in this diabetes-related disease. Therefore, this study aims to investigate the effect of PACAP against hyperglycemia-induced inflammation. To better resemble the natural conditions of corneal epithelium in vivo, an air-liquid interface (ALI) culture of the corneal epithelial cells was performed. The ALI corneal epithelium was cultured under high-glucose conditions to generate a model of DK. Our model reproduced well-established molecular and cellular characteristics of this pathology, including barrier thickness decrease and inflammation, with increased expression of IL-1β, TNF-α, and p-NF-kB. Our results indicated that PACAP significantly reduced the levels of proinflammatory cytokines IL-1β and TNF-α and inhibited the activation of NF-kB, an important mediator of inflammation. Moreover, PACAP improved epithelial morphology and corneal barrier thickness, suggesting its therapeutic potential in the treatment of DK.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"192 ","pages":"Article 171432"},"PeriodicalIF":2.8,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144656020","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-07-12DOI: 10.1016/j.peptides.2025.171430
Laure Guilhaudis , Taylor S. Cunning , Jack J. Delaney , Nigel G. Ternan , Milena Mechkarska , Samir Attoub , J. Michael Conlon
Figainin-2PL (FLGTVLKLGKAIAKTVVPMLTNAMQPKQ.NH2) is active against a range of antibiotic-resistant bacteria as well as human tumor-derived cells. The study aimed to determine the effects of a proline-substitution on the biological potency of the peptide. Secondary structure predictions indicate that figainin-2PL can adopt a helix-turn-helix conformation in membrane-mimetic environments. Circular dichroism spectra are consistent with these predictions. Replacement of the Pro18 residue by either L-Ala, L-Lys or D-Lys increased the extent and stability of the helical domains. All substitutions increased cytotoxic activity against a range of human tumor-derived cells (between 1.5- and 3-fold) but major (between 4- and 10-fold) increases in hemolytic activity against mouse erythrocytes were also observed. While the substitutions Pro18 → L-Ala and Pro18 → L-Ala produced only minor and inconsistent changes in antibacterial activity, the [P18k] analog displayed a 2- to 4-fold greater (MIC and MBC in the range 1–8 µM) against the ESKAPE pathogens Enterococcus faecalis, Enterococcus faecium, Klebsiella pneumoniae and Pseudomonas aeruginosa compared with figainin-2PL and the peptide retained high potency against Acinetobacter baumannii, Escherichia coli, Staphylococcus aureus and Clostridium difficile (MIC and MBC = 2 µM). Consequently, the [P18k] peptide shows therapeutic potential for development into a broad-spectrum, topical antimicrobial agent.
{"title":"Substitution of a proline residue in the frog skin host-defense peptide, figainin-2PL by D-lysine generates an analog with potent activity against antibiotic-resistant ESKAPE pathogens","authors":"Laure Guilhaudis , Taylor S. Cunning , Jack J. Delaney , Nigel G. Ternan , Milena Mechkarska , Samir Attoub , J. Michael Conlon","doi":"10.1016/j.peptides.2025.171430","DOIUrl":"10.1016/j.peptides.2025.171430","url":null,"abstract":"<div><div>Figainin-2PL (FLGTVLKLGKAIAKTVVPMLTNAMQPKQ.NH<sub>2</sub>) is active against a range of antibiotic-resistant bacteria as well as human tumor-derived cells. The study aimed to determine the effects of a proline-substitution on the biological potency of the peptide. Secondary structure predictions indicate that figainin-2PL can adopt a helix-turn-helix conformation in membrane-mimetic environments. Circular dichroism spectra are consistent with these predictions. Replacement of the Pro<sup>18</sup> residue by either L-Ala, L-Lys or D-Lys increased the extent and stability of the helical domains. All substitutions increased cytotoxic activity against a range of human tumor-derived cells (between 1.5- and 3-fold) but major (between 4- and 10-fold) increases in hemolytic activity against mouse erythrocytes were also observed. While the substitutions Pro<sup>18</sup> → L-Ala and Pro<sup>18</sup> → L-Ala produced only minor and inconsistent changes in antibacterial activity, the [P18k] analog displayed a 2- to 4-fold greater (MIC and MBC in the range 1–8 µM) against the ESKAPE pathogens <em>Enterococcus faecalis</em>, <em>Enterococcus faecium, Klebsiella pneumoniae</em> and <em>Pseudomonas aeruginosa</em> compared with figainin-2PL and the peptide retained high potency against <em>Acinetobacter baumannii</em>, <em>Escherichia coli, Staphylococcus aureus</em> and <em>Clostridium difficile</em> (MIC and MBC = 2 µM). Consequently, the [P18k] peptide shows therapeutic potential for development into a broad-spectrum, topical antimicrobial agent.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"192 ","pages":"Article 171430"},"PeriodicalIF":2.8,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144637713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Phoenixin (PNX), first discovered in the rat hypothalamus, was initially identified as a reproductive peptide. PNX-14 (14 amino acid isoform) has also been shown to function in cardiovascular regulation, neuroprotection, glucose metabolism, appetite, anxiety, and memory. We aimed to investigate the potential therapeutic role of PNX-14 in acetic acid (AA)-induced ulcerative colitis. Rats were given intrarectally 1 ml saline (control) or 5 % AA (colitis groups). The control group was treated intraperitoneally with saline, while the colitis groups were treated intraperitoneally with saline or PNX-14 (50 μg/kg/d) or gonadotrophin-releasing hormone (GnRH)-antagonist cetrorelix (CTX; 100 µg/kg/d) or CTX and PNX-14 or sulfasalazine as a positive control (100 mg/kg/d) instantly and once a day for 3 days following colitis induction. Colonic samples were evaluated histologically and biochemically [malondialdehyde (MDA), glutathione (GSH), myeloperoxidase (MPO), chemiluminescence (CL), pro-inflammatory cytokines (tumor necrosis factor-α, interferon-γ, interleukin (IL)-1β, IL-6, IL-8), caspase-3, and 8-hydroxy-2’-deoxyguanosine (8-OHdG) measurements] on the 3rd day. Elevated damage scores (macroscopic and microscopic), MPO, MDA, caspase-3, cytokines, and CL values, and decreased GSH levels of the colitis group were reversed by PNX-14 treatment (p < 0.05–0.001). CTX or CTX plus PNX-14 reduced damage scores, caspase-3, 8-OHdG, cytokines, and CL values (p < 0.05–0.001). Sulfasalazine treatment improved all parameters except MDA and GSH. PNX-14, which alleviates macroscopic, histological and biochemical parameters, can be considered as a potential therapeutic agent in ulcerative colitis with its anti-inflammatory, antioxidant and anti-apoptotic actions. Furthermore, despite its effects as an GnRH-antagonist, CTX has also revealed a similar beneficial role as PNX-14 in this ulcerative colitis model.
{"title":"Phoenixin-14 ameliorates acetic acid-induced ulcerative colitis in rats via antioxidant, anti-inflammatory and anti-apoptotic mechanisms","authors":"Hülya Buzcu , Meral Yüksel , Seda Kırmızıkan , Esra Çikler , Berna Karakoyun","doi":"10.1016/j.peptides.2025.171431","DOIUrl":"10.1016/j.peptides.2025.171431","url":null,"abstract":"<div><div>Phoenixin (PNX), first discovered in the rat hypothalamus, was initially identified as a reproductive peptide. PNX-14 (14 amino acid isoform) has also been shown to function in cardiovascular regulation, neuroprotection, glucose metabolism, appetite, anxiety, and memory. We aimed to investigate the potential therapeutic role of PNX-14 in acetic acid (AA)-induced ulcerative colitis. Rats were given intrarectally 1 ml saline (control) or 5 % AA (colitis groups). The control group was treated intraperitoneally with saline, while the colitis groups were treated intraperitoneally with saline or PNX-14 (50 μg/kg/d) or gonadotrophin-releasing hormone (GnRH)-antagonist cetrorelix (CTX; 100 µg/kg/d) or CTX and PNX-14 or sulfasalazine as a positive control (100 mg/kg/d) instantly and once a day for 3 days following colitis induction. Colonic samples were evaluated histologically and biochemically [malondialdehyde (MDA), glutathione (GSH), myeloperoxidase (MPO), chemiluminescence (CL), pro-inflammatory cytokines (tumor necrosis factor-α, interferon-γ, interleukin (IL)-1β, IL-6, IL-8), caspase-3, and 8-hydroxy-2’-deoxyguanosine (8-OHdG) measurements] on the 3rd day. Elevated damage scores (macroscopic and microscopic), MPO, MDA, caspase-3, cytokines, and CL values, and decreased GSH levels of the colitis group were reversed by PNX-14 treatment (p < 0.05–0.001). CTX or CTX plus PNX-14 reduced damage scores, caspase-3, 8-OHdG, cytokines, and CL values (p < 0.05–0.001). Sulfasalazine treatment improved all parameters except MDA and GSH. PNX-14, which alleviates macroscopic, histological and biochemical parameters, can be considered as a potential therapeutic agent in ulcerative colitis with its anti-inflammatory, antioxidant and anti-apoptotic actions. Furthermore, despite its effects as an GnRH-antagonist, CTX has also revealed a similar beneficial role as PNX-14 in this ulcerative colitis model.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"192 ","pages":"Article 171431"},"PeriodicalIF":2.8,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144634082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-07-11DOI: 10.1016/j.peptides.2025.171428
Damien Gruson , Gaetano Caforio , Daniel D’Angela
Heart failure (HF) remains a significant global health challenge, requiring cost-effective strategies to optimize patient outcomes and resource allocation. Natriuretic peptide (NP) testing has demonstrated substantial clinical and economic value in HF diagnosis, risk stratification, and management. This article examines the international evidence supporting NP testing, highlighting its role in reducing hospitalizations, optimizing medication use, and lowering healthcare expenditures. Addressing disparities in access and reimbursement policies can further enhance its adoption and impact across healthcare systems.
{"title":"Maximizing cost savings in heart failure management: The economic value of natriuretic peptide testing","authors":"Damien Gruson , Gaetano Caforio , Daniel D’Angela","doi":"10.1016/j.peptides.2025.171428","DOIUrl":"10.1016/j.peptides.2025.171428","url":null,"abstract":"<div><div>Heart failure (HF) remains a significant global health challenge, requiring cost-effective strategies to optimize patient outcomes and resource allocation. Natriuretic peptide (NP) testing has demonstrated substantial clinical and economic value in HF diagnosis, risk stratification, and management. This article examines the international evidence supporting NP testing, highlighting its role in reducing hospitalizations, optimizing medication use, and lowering healthcare expenditures. Addressing disparities in access and reimbursement policies can further enhance its adoption and impact across healthcare systems.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"192 ","pages":"Article 171428"},"PeriodicalIF":2.8,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144626812","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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