Peptides最新文献

{"title":"Plasma angiotensinogen is associated with higher 24-hour ambulatory blood pressure independently of plasma angiotensin II in obese men","authors":"Camilla L. Asferg ,&nbsp;Ulrik B. Andersen ,&nbsp;Jørgen L. Jeppesen","doi":"10.1016/j.peptides.2025.171410","DOIUrl":"10.1016/j.peptides.2025.171410","url":null,"abstract":"<div><div>The introduction of liver-targeted antisense oligonucleotides and small interfering ribonucleic acids that inhibit hepatic angiotensinogen synthesis has led to renewed interest in the role of angiotensinogen in hypertension. Therefore, we decided to do further angiotensinogen analyses in a hypertension research program, where we found that obese hypertensive men, given their high salt intake and high 24-hour ambulatory blood pressure (ABP), had higher than expected renin-angiotensin-system (RAS) activity. In a cross-sectional study, we examined 64 newly diagnosed treatment-naïve obese hypertension men (body mass index (BMI) ≥ 30 kg/m², 24-hour systolic ABP ≥ 130 mm Hg and/or 24-hour diastolic ABP ≥ 80 mm Hg), and 40 obese normotensive men (BMI ≥30 mg/m², 24-hour systolic ABP &lt;130 and 24-hour diastolic ABP &lt;80 mm Hg). Blood for biochemical evaluation of the RAS was drawn after 60 minutes rest in the supine position. We applied multiple linear regression analysis to explore independent associations. The obese hypertensive men had a higher mean fasting plasma concentration of angiotensinogen than the obese normotensive men (970.4 ± 214.3 nmol/L versus 868.4 ± 173.0 nmol/L, <em>P</em> = 0.013). Adjusted for age and angiotensin II, angiotensinogen was significantly associated with 24-hour systolic ABP (regression coefficient±standard error (mm Hg/100 nmol/L angiotensinogen): 1.8 ± 0.6, <em>P</em> = 0.006), 24-hour diastolic ABP (0.8 ± 0.3, <em>P</em> = 0.021), and 24-hour pulse pressure (1.0 ± 0.4, <em>P</em> = 0.028). Thus, plasma angiotensinogen was associated with higher 24-hour ABPs independently of plasma angiotensin II in obese men. However, further studies are warranted to determine whether angiotensinogen is only a risk marker of high BP or has BP raising effects independent of angiotensin II.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"190 ","pages":"Article 171410"},"PeriodicalIF":2.8,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144143284","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}

{"title":"Spexin is a biomarker of the process that regulates leptin sensitivity","authors":"Mohamed Badie Ahmed ,&nbsp;Abdella M. Habib ,&nbsp;Saif Badran ,&nbsp;Abeer Alsherawi ,&nbsp;Asma Syed ,&nbsp;Hoda Khoogaly ,&nbsp;Atalla Hammouda ,&nbsp;Abdul-Badi Abou-Samra ,&nbsp;Suhail A. Doi","doi":"10.1016/j.peptides.2025.171416","DOIUrl":"10.1016/j.peptides.2025.171416","url":null,"abstract":"<div><div>The rising prevalence of obesity poses a critical threat to global health, prompting an urgent need for a comprehensive understanding of its underlying mechanisms. This study aimed to delve into the relationship between obesity, leptin sensitivity, and gut hormones, focusing on spexin, glucagon-like peptide-1 (GLP-1), and gastric inhibitory polypeptide (GIP). We examined patients undergoing body contouring surgeries to assess how these hormones and leptin interact. Blood samples were collected at three different time points, and hormone levels were analyzed. Our findings indicated that increases in GLP-1 and decreases in GIP correlated with improved leptin sensitivity, indicated by decreased plasma leptin levels and associated with increase in steepness of the plasma leptin-spexin slope. These results suggest that spexin may serve as a biomarker for leptin sensitivity, the latter influenced by gut hormones in obese individuals. The study provides further evidence that the modulation of leptin sensitivity by gut hormones could be key in addressing obesity and its metabolic consequences.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"190 ","pages":"Article 171416"},"PeriodicalIF":2.8,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144151405","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}

{"title":"IGF-1 contributes to cardiovascular protection in obesity by upregulating Na+/K+-ATPase activity and modulating key signaling pathways in rats on a high-fat diet","authors":"Katarina Banjac ,&nbsp;Milan Obradovic ,&nbsp;Sonja Zafirovic ,&nbsp;Esma R. Isenovic","doi":"10.1016/j.peptides.2025.171418","DOIUrl":"10.1016/j.peptides.2025.171418","url":null,"abstract":"<div><div>This study examined the ability of insulin-like growth factor-1 (IGF-1) to improve the expression and function of cardiac sodium/potassium adenosine triphosphatase (Na⁺/K⁺-ATPase) and reduce heart hypertrophy in obese rats. Adult male Wistar rats received a standard diet or a high-fat (HF) diet for 12 weeks. A bolus injection of IGF-1 (50 μg/kg, i.p.) was administered to half of the HF rats 24 hours before euthanasia. IGF-1 treatment increased: the activity of Na⁺/K⁺-ATPase and expression of phosphorylated and total Na⁺/K⁺-ATPase α₁ subunit, the phosphorylation of IGF-1 receptor β /insulin receptor β at Tyr¹¹³¹/Tyr¹¹⁴⁶, insulin receptor substrate-1 (IRS-1) at Tyr¹²²², mammalian target of rapamycin (mTOR) at Ser²⁴⁸¹, protein kinase B (Akt) at Ser⁴⁷³ and the expression of type-2 angiotensin II <em>(</em>AngII) receptor (AT₂R). Conversely, IGF-1 reduced the levels of IRS-1 phosphorylated at Ser³⁰⁷, mTOR at Ser²⁴⁴⁸, ribosomal protein p70 S6 kinase (S6K) at Thr⁴²¹/Ser⁴²⁴, and the expression of type-1 Ang II receptor (AT₁R) in the heart, as well as the serum levels of Ang II in obese rats. IGF-1 treatment reduced cardiac mass and elevated mRNA expression of the α-myosin heavy chain (MHC), and the α/β MHC ratio in the hearts of obese rats. The results of this study suggest that the administration of IGF-1 to obese rats reduces the adverse effects of HF diet, potentially by lowering Ang II-mediated activation of mTOR/S6K and enhancing the IRS-1/Akt pathway, which promotes Na⁺/K⁺-ATPase activity in the heart and diminishes cardiac hypertrophy.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"190 ","pages":"Article 171418"},"PeriodicalIF":2.8,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144166990","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}

{"title":"Whole body distribution of the regulatory peptide 26RFa in male and female mice","authors":"Marie Picot ,&nbsp;Mélodie Devère ,&nbsp;Saloua Takhlidjt ,&nbsp;Corentin Guillemot ,&nbsp;Caroline Lusurier ,&nbsp;Gaëtan Prévost ,&nbsp;Nicolas Chartrel ,&nbsp;David Godefroy","doi":"10.1016/j.peptides.2025.171417","DOIUrl":"10.1016/j.peptides.2025.171417","url":null,"abstract":"<div><div>26RFa is a regulatory peptide initially isolated from the brain. 26RFa was found to be involved in the regulation of vital functions such as the regulation of energy and glucose metabolism. However, the whole distribution of 26RFa in the organs/tissues of the organism remains fragmentary although it represents a crucial step to discover novel physiological functions for this regulatory peptide. To this aim, we have generated a mouse line that expresses the fluorescent protein tdTomato in 26RFa-expressing cells, and visualization of tdTomato immunostaining <em>in toto</em> was performed using the tridimensional imaging approach.</div><div>Our observations reveal that 26RFa is largely distributed among the organism of male and female mice. 26RFa-expressing cells were notably found in numerous regions of the central nervous system including the olfactory bulbs, the cortex, the hippocampus, the hypothalamus, the cerebellum, the brainstem and the spinal cord. At the periphery, 26RFa-expressing structures were detected all along the gastrointestinal tract, in the liver, the white adipose tissue, the kidney, the adrenal gland, the lungs, the male and female reproductive tracts, the striated muscles, the thymus and a number of exocrine glands such as the salivary glands, the prostate, the seminal vesicles.</div><div>In conclusion, the present anatomical observations are in agreement with the main physiological functions previously reported for 26RFa such the regulation of energy and glucose metabolism or the control of the hypothalamo-pituitary-gonadal or adrenal axis. However, 26RFa is present in other organs/tissues in which its physiological relevance is totally unknown opening therefore a new field of research for this regulatory peptide.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"190 ","pages":"Article 171417"},"PeriodicalIF":2.8,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144192099","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}

{"title":"Acute effects of peripherally administered nicotine on food intake via the central anorectic peptide nesfatin-1/nucleobindin-2 in adult male rats","authors":"Reiko Saito ,&nbsp;Yukiyo Yamamoto ,&nbsp;Reiji Fukano ,&nbsp;Masatomo Mori ,&nbsp;Takashi Maruyama ,&nbsp;Yoichi Ueta","doi":"10.1016/j.peptides.2025.171409","DOIUrl":"10.1016/j.peptides.2025.171409","url":null,"abstract":"<div><div>Acute/chronic exposure to nicotine modulates feeding behavior in experimental animals and humans. However, how nicotine modulates food intake remains unclear. This study examined the acute effects of the peripheral administration of nicotine on food intake in adult male rats, focusing on the possible involvement of the anorectic peptide nesfatin-1/nucleobindin-2 (NucB2) in the central nervous system (CNS). Initially, cumulative food intake, but not water intake, was significantly decreased 0.5, 1, and 1.5 h after the intraperitoneal administration of nicotine (0.5 mg/kg) in 24h-fasted rats. Subsequently, the double-labeled immunohistochemical study revealed that nesfatin-1/NucB2-immunoreactive (ir) neurons expressed Fos-ir in various nuclei of the hypothalamic and brainstem areas, including the supraoptic nucleus and ventral tegmental areas, 90 min after the intraperitoneal administration of nicotine. Finally, pretreatment with intracerebroventricular administration of antisense RNA against nesfatin-1/NucB2 significantly attenuated the suppression of food intake induced by intraperitoneal nicotine administration. The results indicated that the acute effects of peripherally administered nicotine on the suppression of food intake may be partially involved in nesfatin-1/NucB2-containing neurons in the CNS in male adult rats.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"189 ","pages":"Article 171409"},"PeriodicalIF":2.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143942556","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}

{"title":"JHP-7 (QLLEELKR), a heptapeptide derived from Jinhua ham, may ameliorate intrauterine adhesion (IUA) via inhibiting inflammatory response and apoptosis","authors":"Yixiang Wang ,&nbsp;Yang Wu ,&nbsp;Luming Wu ,&nbsp;Xue Fan ,&nbsp;Tong Chen ,&nbsp;Jijun Tao ,&nbsp;Shiyan Tu ,&nbsp;Yiqing Wang ,&nbsp;Xuehong Zhang","doi":"10.1016/j.peptides.2025.171406","DOIUrl":"10.1016/j.peptides.2025.171406","url":null,"abstract":"<div><h3>Objective</h3><div>This study aimed to investigate the effect of <strong>JHP-7</strong>(QLLEELKR) derived from Jinhua ham on IUA, in order to provide new methods and new ideas for the clinical treatment of IUA.</div></div><div><h3>Methods</h3><div>The <strong>JHP-7</strong> was synthesized by solid-phase peptide synthesis (SPPS). An in vitro model (human endometrial epithelial cells (HEECs) induced by 10 ng/mL TGF-β1) and an in vivo model (C57BL/6 mice induced by mechanical curettage and LPS stimulation) were used in the study. In vitro, HEEC were co-cultured with TGF-β1with or without <strong>JHP-7</strong> (1 μM and 10 μM) for 48 h, followed by RT-qPCR and Western blotting analysis. Meanwhile, the fluorescent ROS probe was employed to assess oxidative stress levels. In vivo, IUA mice were preventively treated with <strong>JHP-7</strong> (150 μg/kg/d and 300 μg/kg/d) for 14 days, after which uterine tissues were collected for histopathological evaluation using H&amp;E and Masson staining, as well as molecular analysis <em>via</em> RT-qPCR and Western blotting to measure mRNA and protein expression levels.</div></div><div><h3>Results</h3><div>In vitro, <strong>JHP-7</strong> significantly inhibited the expression of proinflammatory and fibrosis markers, reduced the ROS, and protected endometrial function. Further studies showed that <strong>JHP-7</strong> inhibited the apoptosis of TGF-β1-induced HEECs, and reduced the expression of TLR4, p-NF-κB, and p-MAPK. In vivo, <strong>JHP-7</strong> significantly improved the uterine morphology and reduced collagen deposition in IUA mice. Reduced expression of TLR4, MyD88, p-NF-κB, p-MAPK and up-regulating expression of Bcl2 were also detected after <strong>JHP-7</strong> treatment.</div></div><div><h3>Conclusion</h3><div><strong>JHP-7</strong> could ameliorate IUA <em>via</em> inhibiting inflammation and apoptosis, which may be related to the TLR4/MyD88/MAPK/NF-κB signaling pathway.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"188 ","pages":"Article 171406"},"PeriodicalIF":2.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143824434","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}

{"title":"Oxyntomodulin - past, present and future","authors":"Jens Juul Holst ,&nbsp;Mette M. Rosenkilde","doi":"10.1016/j.peptides.2025.171393","DOIUrl":"10.1016/j.peptides.2025.171393","url":null,"abstract":"<div><div>Almost since its discovery, glucagon was suspected to be formed in the gastrointestinal tract, and the L-cells were shown to contain glucagon-like immunoreactivity. This was due to the presence of two peptides that both contained the full glucagon sequence:glicentin of 69 amino acids and oxyntomodulin of 37 amino acids. While glicentin is a part of the glucagon precursor, proglucagon, and probably is inactive, oxyntomodulin, a fragment of glicentin, interacts although weakly with the glucagon as well as the GLP-1 receptor. However, in agreement with these activities, oxyntomodulin inhibited appetite and food intake in humans and inspired development of long acting, potent glucagon-GLP-1 co-agonists. Several such co-agonists are currently in clinical development and show promise because they combine GLP-1 like activities with those of glucagon agonism: additive weight loss and a stimulation of hepatic lipid metabolism with unique effectiveness on hepatic steatosis. They may therefore be effective in the treatment of metabolic dysfunction-associated steatotic liver disease (MASLD).</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"188 ","pages":"Article 171393"},"PeriodicalIF":2.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143788497","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}

{"title":"Peptide therapeutics: current status and future opportunity with focus on nose-to-brain delivery☆","authors":"Eva-Maria Jülke,&nbsp;Annette G. Beck-Sickinger","doi":"10.1016/j.peptides.2025.171404","DOIUrl":"10.1016/j.peptides.2025.171404","url":null,"abstract":"<div><div>Peptide drugs are a highly diverse group of therapeutic agents. Over the last decade, more than 40 peptides have been approved for clinical use. They target different structures, ranging from G protein-coupled receptors (GPCRs) to pathogens and are used to treat a variety of indications, including metabolic disorders, genetic diseases, acute illnesses and more. Structurally, peptide therapeutics are a heterogeneous class. This diversity allows them to bridge the gap between small molecules and biologics. However, limited metabolic stability and bioavailability must be addressed. Strategies to improve the half-life include backbone and sequence modification, cyclization and the addition of stabilizing moieties. Great strides have been made in recent years towards achieving sufficient drug uptake for oral application have been achieved within recent years. However, these methods require specialized peptide design or involve permeabilization of the gastrointestinal tract. Consequently, other routes of administration are being explored. One promising approach is the nasal application of peptides. This method can be used for systemic uptake, but also allows for direct nose-to-brain delivery of compounds. While successful nose-to-brain delivery is already used in the clinic, the underlining mechanisms are poorly understood. Strategies for rational optimization are needed to make this method more applicable to a wider range of compounds. Overall, approved peptide therapeutics cover a wide range of applications and have demonstrated a growing and novel potential in recent drug discovery.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"188 ","pages":"Article 171404"},"PeriodicalIF":2.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143847670","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}

{"title":"Irisin prevents visceral hypersensitivity and colonic hyperpermeability in a rat model of irritable bowel syndrome","authors":"Tsukasa Nozu ,&nbsp;Saori Miyagishi ,&nbsp;Masatomo Ishioh ,&nbsp;Kaoru Takakusaki ,&nbsp;Toshikatsu Okumura","doi":"10.1016/j.peptides.2025.171394","DOIUrl":"10.1016/j.peptides.2025.171394","url":null,"abstract":"<div><div>Visceral hypersensitivity and impaired gut barrier function, accompanied by minor inflammation, are crucial components of the pathophysiology of irritable bowel syndrome (IBS). Research has demonstrated that corticotropin-releasing factor (CRF) and toll-like receptor 4 (TLR4) signaling mutually activate to produce proinflammatory cytokines, which modulate these gastrointestinal changes. Irisin, a myokine, has been shown to inhibit TLR4-proinflammatory cytokine signaling, thereby improving inflammation driven by obesity and metabolic syndrome. Based on this, we hypothesized that irisin could improve visceral hypersensitivity and impaired gut barrier function induced by lipopolysaccharide (LPS) or CRF (IBS rat models), and tested this hypothesis. The visceral pain threshold, triggered by colonic balloon distention, was assessed by electrophysiologically monitoring abdominal muscle contractions in male Sprague-Dawley rats. Colonic permeability was evaluated by measuring the amount of Evans blue dye absorbed within the colonic tissue. Intraperitoneal irisin prevented LPS-induced visceral hypersensitivity and colonic hyperpermeability in a dose-dependent manner. Irisin also prevented CRF-induced gastrointestinal alterations. The beneficial effects of irisin in the LPS model were reversed by compound C, an AMP-activated protein kinase (AMPK) inhibitor; N^G-nitro-L-arginine methyl ester, a nitric oxide (NO) synthesis inhibitor; sulpiride or domperidone, a dopamine D₂ receptor antagonist; atropine and intracisternal injection of SB-334867, a selective orexin 1 receptor antagonist. Overall, these findings suggest that irisin improves visceral sensation and colonic barrier function through AMPK, NO and dopamine D₂, cholinergic and brain orexin signaling in IBS model. Thus, irisin may be a promising therapeutic agent for treating IBS.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"188 ","pages":"Article 171394"},"PeriodicalIF":2.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143726086","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}

{"title":"Spexin expression in the human bile duct and perihilar cholangiocarcinoma","authors":"Sara Huber ,&nbsp;Theresia Fitzner ,&nbsp;René G. Feichtinger ,&nbsp;Theo Kraus ,&nbsp;Stefanie Gaisbauer ,&nbsp;Sarah Hochmann ,&nbsp;Karl Sotlar ,&nbsp;Barbara Kofler ,&nbsp;Martin Varga","doi":"10.1016/j.peptides.2025.171405","DOIUrl":"10.1016/j.peptides.2025.171405","url":null,"abstract":"<div><div>The bile duct transports bile fluid from the liver to the gallbladder and small intestine. It contains bioactive peptides, including galanin (GAL) and its receptors (GAL_1–3-R). Spexin (SPX), a member of the GAL peptide family, activates GAL₂-R and GAL₃-R. Its expression in perihilar bile ducts or in perihilar cholangiocarcinoma (pCCA), the most common biliary cancer, is largely unknown. This study investigated SPX expression in healthy, cholestatic, and malignant bile duct tissues. Immunohistochemistry was used to evaluate SPX in healthy (n = 4), peritumoral (PIT) (n = 23) and pCCA (n = 34) tissues. Score values of SPX expression were calculated and statistically analyzed. In healthy and PIT tissues with or without cholestasis, SPX expression was predominantly observed in cholangiocytes and nerve fibers. In pCCA, tumor cells also expressed SPX. SPX levels were similar across healthy, peritumoral, and cholangiocytes/tumor cells. In a small pCCA patient cohort (n = 19), SPX expression did not correlate with tumor grade or patient survival (<em>p</em> = 0.0838). The substantial expression of SPX in cholangiocytes and nerve fibers in the bile duct indicates that SPX contributes via galaninergic signaling to gall bladder function. The presence of SPX in submucosal nerve fibers suggests a neuromodulatory role, possibly involving bile duct motility. SPX expression did not correlate with survival in pCCA, whereas previous findings on GAL suggest a prognostic value. This highlights the need for joint studies of SPX and GAL in larger cohorts.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"188 ","pages":"Article 171405"},"PeriodicalIF":2.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143803919","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}