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Strzelczyk J, Bocian-Jastrzębska A, Strzelczyk JK, Wójcik-Giertuga M, Biernacki K, Kajdaniuk D, Kos-Kudła B. Adipokines in Neuroendocrine Tumors: An Evaluation of the Serum Levels of Ghrelin and Leptin. Int J Mol Sci 2024; 25:9820. [PMID: 39337308 PMCID: PMC11432421 DOI: 10.3390/ijms25189820] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2024] [Revised: 09/03/2024] [Accepted: 09/08/2024] [Indexed: 09/30/2024] Open
Abstract
Neuroendocrine tumors (NETs) are a heterogeneous group of tumors that are characteristically different from other malignancies. The difference is not only in the prognosis, which is usually more favorable in such patients, but also in the high clinical progression of the disease, where NET patients do not experience the cachexia typical of other malignancies. The purposes of this study were to evaluate the ghrelin and leptin levels in a group of patients diagnosed with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) and bronchopulmonary neuroendocrine tumors (BP-NETs) and to analyze the relationship between the body mass index (BMI), cachexia and selected NET markers. The study group comprised 52 patients with GEP-NETs and BP-NETs, while the controls comprised 67 healthy volunteers. The ghrelin and leptin concentrations were determined in both groups. The concentrations of chromogranin A, serotonin, 5-hydroxyindoleacetic acid (5-HIAA), total cholesterol, triglycerides and glucose were determined in the study group. Characteristics of the study group and of the controls were defined by age, sex and BMI, and the effects of these factors on the ghrelin and leptin concentrations were assessed. The data obtained were subject to statistical analysis. The study cohort showed higher levels of ghrelin as compared to the controls (142.31 ± 26.00 vs. 121.49 ± 35.45, p = 0.016), and no statistical difference in the levels of leptin (11.15 ± 9.6 vs. 12.94 ± 20.30, p = 0.439) were observed. Significantly lower levels of leptin were found in patients with the small intestine primary location, as compared to individuals with primary locations in the lungs and the pancreas (4.9 ± 6.49 vs. 16.97 ± 15.76, p = 0.045, and 4.9 ± 6.49 vs. 12.89 ± 8.56, p = 0.016, respectively). A positive correlation was observed between the leptin levels and the BMIs in both the study group (rS = 0.33, p = 0.016) and the controls (rS = 0.41, p = 0.001). The study group showed a negative correlation between the leptin levels and 5-HIAA (rS = -0.32, p = 0.026) and a negative correlation between the leptin levels and Ki-67 (rS = -0.33, p = 0.018). The control group showed negative correlations between the ghrelin and the volunteer age (rS = -0.41, p = 0.008), the leptin and the volunteer age (rS = -0.44, p < 0.001), the leptin and total cholesterol (rS = -0.24, p < 0.049) as well as the leptin and triglycerides (rS = -0.33, p < 0.006). The current study emphasized the importance of the markers' determination, where ghrelin appears as a valuable diagnostic biomarker in NETs, probably responsible for maintaining a normal BMI, despite the progression of the disease.
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Affiliation(s)
- Janusz Strzelczyk
- Department of Endocrinology and Neuroendocrine Tumors, Department of Pathophysiology and Endocrinology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, 40-514 Katowice, Poland; (A.B.-J.); (M.W.-G.); (B.K.-K.)
| | - Agnes Bocian-Jastrzębska
- Department of Endocrinology and Neuroendocrine Tumors, Department of Pathophysiology and Endocrinology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, 40-514 Katowice, Poland; (A.B.-J.); (M.W.-G.); (B.K.-K.)
| | - Joanna Katarzyna Strzelczyk
- Department of Medical and Molecular Biology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, 41-808 Katowice, Poland; (J.K.S.); (K.B.)
| | - Monika Wójcik-Giertuga
- Department of Endocrinology and Neuroendocrine Tumors, Department of Pathophysiology and Endocrinology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, 40-514 Katowice, Poland; (A.B.-J.); (M.W.-G.); (B.K.-K.)
| | - Krzysztof Biernacki
- Department of Medical and Molecular Biology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, 41-808 Katowice, Poland; (J.K.S.); (K.B.)
| | - Dariusz Kajdaniuk
- Department of Pathophysiology and Endocrinology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, 41-808 Katowice, Poland;
| | - Beata Kos-Kudła
- Department of Endocrinology and Neuroendocrine Tumors, Department of Pathophysiology and Endocrinology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, 40-514 Katowice, Poland; (A.B.-J.); (M.W.-G.); (B.K.-K.)
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Bai J, Wang Y, Li Y, Liu Y, Wang S. Protective effect of ghrelin in oxidative stress-induced age-related macular degeneration in vitro and in vivo. Mol Med 2024; 30:142. [PMID: 39251914 PMCID: PMC11384690 DOI: 10.1186/s10020-024-00920-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2024] [Accepted: 09/01/2024] [Indexed: 09/11/2024] Open
Abstract
Oxidative damage to human retinal pigment epithelial (RPE) cells is the main cause of age-related macular degeneration (AMD), in our previous work, we showed that ghrelin has an antioxidative effect on human lens epithelium (HLE) cells, however, the studies of using ghrelin in treating the degenerative diseases of the retina have rarely been reported. In this article, we assessed the effect of ghrelin on preventing oxidative stress induced by hydrogen peroxide (H2O2) in ARPE-19 cells and its mechanism. We observed that pretreatment with ghrelin protected ARPE-19 cells from H2O2-induced cell oxidative injuries and apoptosis responses. Furthermore, an oxidative stress-induced mouse model of AMD was established via injection of sodium iodate (NaIO3) to tail veins, and treatment with ghrelin preserved retinal function, and protected photoreceptors.
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Affiliation(s)
- Jie Bai
- Department of Ophthalmology, the Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang University, Yiwu, 322000, Zhejiang, P. R. China.
| | - Yanqing Wang
- Department of Ophthalmology, the Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang University, Yiwu, 322000, Zhejiang, P. R. China
| | - Yanze Li
- Department of Ophthalmology, the Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang University, Yiwu, 322000, Zhejiang, P. R. China
| | - Yan Liu
- Department of Ophthalmology and Otorhinolaryngology, Yiwu Second People's Hospital, Yiwu, 322000, Zhejiang, P. R. China
| | - Shan Wang
- Department of Oral Pathology, School of Stomatology, Hainan Medical University, Haikou, 571199, P. R. China.
- Department of Oral Pathology, School of Stomatology, Hainan Medical College, Haikou, 571199, P. R. China.
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Trotta MC, Gesualdo C, Russo M, Lepre CC, Petrillo F, Vastarella MG, Nicoletti M, Simonelli F, Hermenean A, D’Amico M, Rossi S. Changes in Circulating Acylated Ghrelin and Neutrophil Elastase in Diabetic Retinopathy. MEDICINA (KAUNAS, LITHUANIA) 2024; 60:118. [PMID: 38256379 PMCID: PMC10820226 DOI: 10.3390/medicina60010118] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/13/2023] [Revised: 01/04/2024] [Accepted: 01/05/2024] [Indexed: 01/24/2024]
Abstract
Background and Objectives: The role and the levels of ghrelin in diabetes-induced retinal damage have not yet been explored. The present study aimed to measure the serum levels of total ghrelin (TG), and its acylated (AG) and des-acylated (DAG) forms in patients with the two stages of diabetic retinopathy (DR), non-proliferative (NPDR) and proliferative (PDR). Moreover, the correlation between serum ghrelin and neutrophil elastase (NE) levels was investigated. Materials and Methods: The serum markers were determined via enzyme-linked immunosorbent assays in 12 non-diabetic subjects (CTRL), 15 diabetic patients without DR (Diabetic), 15 patients with NPDR, and 15 patients with PDR. Results: TG and AG serum levels were significantly decreased in Diabetic (respectively, p < 0.05 and p < 0.01 vs. CTRL), NPDR (p < 0.01 vs. Diabetic), and in PDR patients (p < 0.01 vs. NPDR). AG serum levels were inversely associated with DR abnormalities (microhemorrhages, microaneurysms, and exudates) progression (r = -0.83, p < 0.01), serum neutrophil percentage (r = -0.74, p < 0.01), and serum NE levels (r = -0.73, p < 0.01). The latter were significantly increased in the Diabetic (p < 0.05 vs. CTRL), NPDR (p < 0.01 vs. Diabetic), and PDR (p < 0.01 vs. PDR) groups. Conclusions: The two DR stages were characterized by decreased AG and increased NE levels. In particular, serum AG levels were lower in PDR compared to NPDR patients, and serum NE levels were higher in the PDR vs. the NPDR group. Together with the greater presence of retinal abnormalities, this could underline a distinctive role of AG in PDR compared to NPDR.
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Affiliation(s)
- Maria Consiglia Trotta
- Department of Experimental Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (M.C.T.); (C.C.L.); (F.P.); (M.D.)
| | - Carlo Gesualdo
- Multidisciplinary Department of Medical, Surgical and Dental Sciences, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (C.G.); (M.N.); (F.S.)
| | - Marina Russo
- PhD Course in National Interest in Public Administration and Innovation for Disability and Social Inclusion, Department of Mental, Physical Health and Preventive Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy;
- School of Pharmacology and Clinical Toxicology, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy
| | - Caterina Claudia Lepre
- Department of Experimental Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (M.C.T.); (C.C.L.); (F.P.); (M.D.)
- PhD Course in Translational Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy;
| | - Francesco Petrillo
- Department of Experimental Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (M.C.T.); (C.C.L.); (F.P.); (M.D.)
- PhD Course in Translational Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy;
| | - Maria Giovanna Vastarella
- PhD Course in Translational Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy;
| | - Maddalena Nicoletti
- Multidisciplinary Department of Medical, Surgical and Dental Sciences, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (C.G.); (M.N.); (F.S.)
| | - Francesca Simonelli
- Multidisciplinary Department of Medical, Surgical and Dental Sciences, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (C.G.); (M.N.); (F.S.)
| | - Anca Hermenean
- “Aurel Ardelean” Institute of Life Sciences, Vasile Goldis Western University of Arad, 310144 Arad, Romania;
| | - Michele D’Amico
- Department of Experimental Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (M.C.T.); (C.C.L.); (F.P.); (M.D.)
| | - Settimio Rossi
- Multidisciplinary Department of Medical, Surgical and Dental Sciences, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (C.G.); (M.N.); (F.S.)
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Merabet N, Ramoz N, Boulmaiz A, Bourefis A, Benabdelkrim M, Djeffal O, Moyse E, Tolle V, Berredjem H. SNPs-Panel Polymorphism Variations in GHRL and GHSR Genes Are Not Associated with Prostate Cancer. Biomedicines 2023; 11:3276. [PMID: 38137497 PMCID: PMC10741232 DOI: 10.3390/biomedicines11123276] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2023] [Revised: 12/05/2023] [Accepted: 12/09/2023] [Indexed: 12/24/2023] Open
Abstract
Prostate cancer (PCa) is a major public health problem worldwide. Recent studies have suggested that ghrelin and its receptor could be involved in the susceptibility to several cancers such as PCa, leading to their use as an important predictive way for the clinical progression and prognosis of cancer. However, conflicting results of single nucleotide polymorphisms (SNPs) with ghrelin (GHRL) and its receptor (GHSR) genes were demonstrated in different studies. Thus, the present case-control study was undertaken to investigate the association of GHRL and GHSR polymorphisms with the susceptibility to sporadic PCa. A cohort of 120 PCa patients and 95 healthy subjects were enrolled in this study. Genotyping of six SNPs was performed: three tag SNPs in GHRL (rs696217, rs4684677, rs3491141) and three tag SNPs in the GHSR (rs2922126, rs572169, rs2948694) using TaqMan. The allele and genotype distribution, as well as haplotypes frequencies and linked disequilibrium (LD), were established. Multifactor dimensionality reduction (MDR) analysis was used to study gene-gene interactions between the six SNPs. Our results showed no significant association of the target polymorphisms with PCa (p > 0.05). Nevertheless, SNPs are often just markers that help identify or delimit specific genomic regions that may harbour functional variants rather than the variants causing the disease. Furthermore, we found that one GHSR rs2922126, namely the TT genotype, was significantly more frequent in PCa patients than in controls (p = 0.040). These data suggest that this genotype could be a PCa susceptibility genotype. MDR analyses revealed that the rs2922126 and rs572169 combination was the best model, with 81.08% accuracy (p = 0.0001) for predicting susceptibility to PCa. The results also showed a precision of 98.1% (p < 0.0001) and a PR-AUC of 1.00. Our findings provide new insights into the influence of GHRL and GHSR polymorphisms and significant evidence for gene-gene interactions in PCa susceptibility, and they may guide clinical decision-making to prevent overtreatment and enhance patients' quality of life.
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Affiliation(s)
- Nesrine Merabet
- Laboratory of Applied Biochemistry and Microbiology, Department of Biochemistry, Faculty of Sciences, Badji Mokhtar University, Annaba 23000, Algeria; (A.B.); (A.B.); (M.B.)
- Unit 85 PRC (Physiology of Reproduction and Behavior), Centre INRAe of Tours, University of Tours, 37380 Nouzilly, France;
| | - Nicolas Ramoz
- University Paris Cité, INSERM U1266, Institute of Psychiatry and Neuroscience of Paris (IPNP), 75014 Paris, France; (N.R.); (V.T.)
| | - Amel Boulmaiz
- Laboratory of Applied Biochemistry and Microbiology, Department of Biochemistry, Faculty of Sciences, Badji Mokhtar University, Annaba 23000, Algeria; (A.B.); (A.B.); (M.B.)
| | - Asma Bourefis
- Laboratory of Applied Biochemistry and Microbiology, Department of Biochemistry, Faculty of Sciences, Badji Mokhtar University, Annaba 23000, Algeria; (A.B.); (A.B.); (M.B.)
| | - Maroua Benabdelkrim
- Laboratory of Applied Biochemistry and Microbiology, Department of Biochemistry, Faculty of Sciences, Badji Mokhtar University, Annaba 23000, Algeria; (A.B.); (A.B.); (M.B.)
| | - Omar Djeffal
- Private Medical Uro-Chirurgical Cabinet, Cité SafSaf, BatR02 n°S01, Annaba 23000, Algeria;
| | - Emmanuel Moyse
- Unit 85 PRC (Physiology of Reproduction and Behavior), Centre INRAe of Tours, University of Tours, 37380 Nouzilly, France;
| | - Virginie Tolle
- University Paris Cité, INSERM U1266, Institute of Psychiatry and Neuroscience of Paris (IPNP), 75014 Paris, France; (N.R.); (V.T.)
| | - Hajira Berredjem
- Laboratory of Applied Biochemistry and Microbiology, Department of Biochemistry, Faculty of Sciences, Badji Mokhtar University, Annaba 23000, Algeria; (A.B.); (A.B.); (M.B.)
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Larsson SC, Höijer J, Sun J, Li X, Burgess S, Michaëlsson K. Genome-Wide Association and Two-Sample Mendelian Randomization Analyses of Plasma Ghrelin and Gastrointestinal Cancer Risk. Cancer Epidemiol Biomarkers Prev 2023; 32:1771-1776. [PMID: 37791980 PMCID: PMC10690139 DOI: 10.1158/1055-9965.epi-23-0757] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2023] [Revised: 08/23/2023] [Accepted: 10/02/2023] [Indexed: 10/05/2023] Open
Abstract
BACKGROUND Observational studies have suggested that the gut hormone ghrelin is an early marker of future risk of developing gastrointestinal cancer. However, whether ghrelin is a causal risk factor remains unclear. We conducted a genome-wide association study (GWAS) of plasma ghrelin and used Mendelian randomization (MR) to investigate the possible causal association between ghrelin and gastrointestinal cancer risk. METHODS Genetic variants associated with plasma ghrelin were identified in a GWAS comprising 10,742 Swedish adults in the discovery (N = 6,259) and replication (N = 4,483) cohorts. The association between ghrelin and gastrointestinal cancer was examined through a two-sample MR analysis using the identified genetic variants as instruments and GWAS data from the UK Biobank, FinnGen, and a colorectal cancer consortium. RESULTS GWAS found associations between multiple genetic variants within ±200 kb of the GHRL gene and plasma ghrelin. A two-sample MR analysis revealed that genetically predicted higher plasma ghrelin levels were associated with a lower risk of gastrointestinal cancer in UK Biobank and in a meta-analysis of the UK Biobank and FinnGen studies. The combined OR per approximate doubling of genetically predicted plasma ghrelin was 0.91 (95% confidence interval, 0.85-0.99; P = 0.02). Colocalization analysis revealed limited evidence of shared causal variants for plasma ghrelin and gastrointestinal cancer at the GHRL locus (posterior probability H4 = 24.5%); however, this analysis was likely underpowered. CONCLUSIONS Our study provides evidence in support of a possible causal association between higher plasma ghrelin levels and a reduced risk of gastrointestinal cancer. IMPACT Elevated plasma ghrelin levels might reduce the risk of gastrointestinal cancer.
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Affiliation(s)
- Susanna C. Larsson
- Unit of Medical Epidemiology, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden
- Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Jonas Höijer
- Unit of Medical Epidemiology, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden
| | - Jing Sun
- Department of Big Data in Health Science, School of Public Health and The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Xue Li
- Department of Big Data in Health Science, School of Public Health and The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Stephen Burgess
- Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom
- MRC Biostatistics Unit, University of Cambridge, Cambridge, United Kingdom
| | - Karl Michaëlsson
- Unit of Medical Epidemiology, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden
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Muszyński S, Hułas-Stasiak M, Dobrowolski P, Arciszewski MB, Hiżewska L, Donaldson J, Mozel S, Rycerz K, Kapica M, Puzio I, Tomaszewska E. Maternal acrylamide exposure changes intestinal epithelium, immunolocalization of leptin and ghrelin and their receptors, and gut barrier in weaned offspring. Sci Rep 2023; 13:10286. [PMID: 37355724 PMCID: PMC10290718 DOI: 10.1038/s41598-023-37590-3] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2023] [Accepted: 06/23/2023] [Indexed: 06/26/2023] Open
Abstract
Acrylamide (ACR) is an amide formed as a byproduct in many heat-processed starchy-rich foods. In utero ACR exposure has been associated with restricted fetal growth, but its effects of postnatal functional development of small intestine is completely unknown. The current study investigated the time- and segment-dependent effects of prenatal ACR exposure on morphological and functional development of small intestine in weaned rat offspring. Four groups of pregnant female Wistar rats were exposed to ACR (3 mg/kg b.w./day) for 0, 5, 10 and 15 days during pregnancy. Basal intestinal morphology, immunolocalization of gut hormones responsible for food intake and proteins of intestinal barrier, activity of the intestinal brush border disaccharidases, apoptosis and proliferation in intestinal mucosa were analyzed in offspring at weaning (postnatal day 21). The results showed that in utero ACR exposure disturbs offspring gut structural and functional postnatal development in a time- and segment-depended manner and even a short prenatal exposure to ACR resulted in changes in intestinal morphology, immunolocalization of leptin and ghrelin and their receptors, barrier function, activity of gut enzymes and upregulation of apoptosis and proliferation. In conclusion, prenatal ACR exposure disturbed the proper postnatal development of small intestine.
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Affiliation(s)
- Siemowit Muszyński
- Department of Biophysics, Faculty of Environmental Biology, University of Life Sciences in Lublin, Akademicka St. 13, 20-950, Lublin, Poland
| | - Monika Hułas-Stasiak
- Department of Functional Anatomy and Cytobiology, Faculty of Biology and Biotechnology, Maria Curie-Sklodowska University, Akademicka St. 19, 20-033, Lublin, Poland
| | - Piotr Dobrowolski
- Department of Functional Anatomy and Cytobiology, Faculty of Biology and Biotechnology, Maria Curie-Sklodowska University, Akademicka St. 19, 20-033, Lublin, Poland
| | - Marcin B Arciszewski
- Department of Animal Anatomy and Histology, Faculty of Veterinary Medicine, University of Life Sciences in Lublin, Akademicka St. 12, 20-950, Lublin, Poland
| | - Ligia Hiżewska
- Department of Animal Anatomy and Histology, Faculty of Veterinary Medicine, University of Life Sciences in Lublin, Akademicka St. 12, 20-950, Lublin, Poland
| | - Janine Donaldson
- School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, 7 York Road, Parktown, Johannesburg, 2193, South Africa
| | - Sylwia Mozel
- Department of Animal Anatomy and Histology, Faculty of Veterinary Medicine, University of Life Sciences in Lublin, Akademicka St. 12, 20-950, Lublin, Poland
| | - Karol Rycerz
- Department of Animal Anatomy and Histology, Faculty of Veterinary Medicine, University of Life Sciences in Lublin, Akademicka St. 12, 20-950, Lublin, Poland
| | - Małgorzata Kapica
- Department of Animal Physiology, Faculty of Veterinary Medicine, University of Life Sciences in Lublin, Akademicka St. 12, 20-950, Lublin, Poland
| | - Iwona Puzio
- Department of Animal Physiology, Faculty of Veterinary Medicine, University of Life Sciences in Lublin, Akademicka St. 12, 20-950, Lublin, Poland
| | - Ewa Tomaszewska
- Department of Animal Physiology, Faculty of Veterinary Medicine, University of Life Sciences in Lublin, Akademicka St. 12, 20-950, Lublin, Poland.
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Tomaszewska E, Rudyk H, Dobrowolski P, Arciszewski MB, Donaldson J, Kras K, Abramowicz B, Kuc D, Muszyński S. Basal Intestinal Morphology, Immunolocalization of Leptin and Ghrelin and Their Receptors in Newborn Wistar Rats after Prenatal Exposure to Fumonisins. Animals (Basel) 2023; 13:ani13091538. [PMID: 37174575 PMCID: PMC10177403 DOI: 10.3390/ani13091538] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2023] [Revised: 04/24/2023] [Accepted: 05/02/2023] [Indexed: 05/15/2023] Open
Abstract
Animal feed is very frequently contaminated with different types of mold, the metabolites of which are toxic to living organisms. Mold-contaminated cereal is rich in heat-resistant and harmful metabolites such as fumonisins (FBs). The amount of FBs consumed as part of animal feed, including livestock feed, is unknown. Therefore, this study aimed to evaluate the effects of maternal oral FB intoxication on basal duodenum morphology and the immunolocalization of gut hormones responsible for food intake (leptin and ghrelin), as well as their receptors, in newborn rat offspring. Pregnant Wistar rats were randomly allocated to one of three groups: a control group or one of two FB-intoxicated groups (60 or 90 mg FB/kg b.w., respectively). Basal morphological duodenal parameters changed in a dose- and sex-dependent manner. The intensity of the ghrelin immunoreaction was unchanged in females, while in males it increased after FB exposure (60 mg/kg b.w.), with a simultaneous decrease in expression of the ghrelin receptor. Leptin and its receptor immunoreaction intensity was decreased in both sexes following FB exposure. The current study highlighted the potential involvement of intestinal ghrelin and leptin in the metabolic disturbances observed later in life in offspring that were prenatally exposed to fumonisins.
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Affiliation(s)
- Ewa Tomaszewska
- Department of Animal Physiology, Faculty of Veterinary Medicine, University of Life Sciences in Lublin, 20-950 Lublin, Poland
| | - Halyna Rudyk
- Department of Animal Physiology, Faculty of Veterinary Medicine, University of Life Sciences in Lublin, 20-950 Lublin, Poland
- Laboratory of Feed Additives and Premixtures Control, State Research Control Institute of Veterinary Drugs and Feed Additives, 79000 Lviv, Ukraine
| | - Piotr Dobrowolski
- Department of Functional Anatomy and Cytobiology, Faculty of Biology and Biotechnology, Maria Curie-Sklodowska University, 20-033 Lublin, Poland
| | - Marcin B Arciszewski
- Department of Animal Anatomy and Histology, Faculty of Veterinary Medicine, University of Life Sciences in Lublin, 20-950 Lublin, Poland
| | - Janine Donaldson
- School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, Parktown, Johannesburg 2193, South Africa
| | - Katarzyna Kras
- Department of Animal Anatomy and Histology, Faculty of Veterinary Medicine, University of Life Sciences in Lublin, 20-950 Lublin, Poland
| | - Beata Abramowicz
- Department and Clinic of Animal Internal Diseases, Faculty of Veterinary Medicine, University of Life Sciences in Lublin, 20-612 Lublin, Poland
| | - Damian Kuc
- Chair and Department of Developmental Dentistry, Medical University of Lublin, 20-081 Lublin, Poland
| | - Siemowit Muszyński
- Department of Biophysics, Faculty of Environmental Biology, University of Life Sciences in Lublin, 20-950 Lublin, Poland
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Bodén S, Harbs J, Sundkvist A, Fuchs K, Myte R, Gylling B, Zingmark C, Löfgren Burström A, Palmqvist R, Harlid S, Van Guelpen B. Plasma Concentrations of Gut Hormones Acyl Ghrelin and Peptide YY and Subsequent Risk of Colorectal Cancer and Molecular Tumor Subtypes. Cancer Prev Res (Phila) 2023; 16:75-87. [PMID: 36367526 PMCID: PMC9900320 DOI: 10.1158/1940-6207.capr-22-0325] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2022] [Revised: 09/30/2022] [Accepted: 11/03/2022] [Indexed: 11/13/2022]
Abstract
Obesity and metabolic dysfunction are implicated in colorectal cancer development. Appetite-regulating gut hormones might have a role in colorectal cancer risk. We investigated whether circulating levels of the gut hormones ghrelin (analyzed as acyl ghrelin) and Peptide YY (PYY) were associated with subsequent colorectal cancer risk, including clinical and molecular tumor subtypes. We also provide descriptive data on these hormones in relation to background participant characteristics and metabolic biomarkers. This population-based study included 1,010 matched case-control pairs with a median of 12.3 years of follow-up. Acyl ghrelin and PYY were measured by multiplex immunoassay. Data on KRAS and BRAF mutations and microsatellite instability (MSI) status were available for 704 and 708 cases, respectively. Conditional logistic regression models estimated association to colorectal cancer risk. Partial correlation and linear regression were used to investigate relationships between background and metabolic variables and variation in plasma gut hormone concentrations. Acyl ghrelin was not clearly associated with colorectal cancer risk (multivariable OR per 1 SD increase: 1.11; 95% CI, 1.00-1.23). Positive associations were observed for specific subtypes, in particular BRAF-mutated colorectal cancer and right-sided colon cancer, although with nonsignificant heterogeneity. PYY was not related to colorectal cancer risk (multivariable OR per 1 SD: 1.04; 95% CI, 0.95-1.14) or any tumor subtype. In the control participants, ghrelin was inversely correlated with BMI, and PYY was positively correlated with C-peptide and insulin levels. These findings provide limited support for a possible role for ghrelin in colorectal cancer development, primarily in specific anatomical and molecular tumor subtypes. PREVENTION RELEVANCE The findings of this study do not support a major role for the metabolic gut hormones ghrelin and PYY in colorectal cancer development but suggest the possibility of an involvement for ghrelin in specific tumor subtypes. Elucidating subtype-specific risk factors and mechanisms of carcinogenesis may have implications for precision prevention.
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Affiliation(s)
- Stina Bodén
- Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden
| | - Justin Harbs
- Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden
| | - Anneli Sundkvist
- Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden
| | - Klara Fuchs
- Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden
| | - Robin Myte
- Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden
| | - Björn Gylling
- Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden
| | - Carl Zingmark
- Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden
| | | | - Richard Palmqvist
- Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden
| | - Sophia Harlid
- Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden
| | - Bethany Van Guelpen
- Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden.,Wallenberg Centre for Molecular Medicine, Umeå University, Umeå, Sweden.,Corresponding Author: Bethany Van Guelpen, Department of Radiation Sciences, Oncology, Umeå University, SE-90187 Umeå, Sweden. E-mail:
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9
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Chen X, Mi J, Huang H, Wang J, Wu Y, Wu X, Zhang S. Ghrelin and ghrelin receptor (GHSR) in Chinese alligator, alligator sinensis: Molecular characterization, tissue distribution and mRNA expression changes during the active and hibernating periods. Gen Comp Endocrinol 2022; 327:114097. [PMID: 35853503 DOI: 10.1016/j.ygcen.2022.114097] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2022] [Revised: 07/02/2022] [Accepted: 07/13/2022] [Indexed: 11/20/2022]
Abstract
The Chinese alligator (Alligator sinensis) is a freshwater crocodilian endemic to China. So far, the endocrine regulation of feeding and growth in Chinese alligator is poorly understood. In this study, the molecular structure and tissue expression profiles of ghrelin and its receptor GHSR in the Chinese alligator were characterized for the first time. The full-length cDNA of ghrelin was 1770 bp, including a 37 bp 5 '-UTR (untranslated region), a 435 bp ORF (open reading frame) and a 1298 bp 3 '-UTR. The ORF encodes a ghrelin precursor, which consists of 145 amino acid residues, including a signal peptide with 52 amino acid residues at the N-terminus, a mature peptide with 28 amino acid residues, and a possibly obestain at the C-terminus. The full-length cDNA of GHSR was 3961 bp, including a 5'-UTR of 375-bp, an ORF of 1059-bp and a 3' -UTR of 2527-bp. The ORF encodes a protein of 352 amino acid residues containing seven transmembrane domains, with multiple N glycosylation modification sites and conserved cysteine residue sites. The active core "GSSF" of Chinese alligator ghrelin was identical to that of mammals and birds, and the ghrelin binding site of GHSR was similar to that of mammals. The amino acid sequences of both ghrelin and GHSR share high identity with American alligator (Alligator mississippiensis) and birds. Ghrelin was highly expressed in cerebrum, mesencephalon, hypothalamus and multiple peripheral tissues, including lung, stomach and intestine, suggesting that it could play functions in paracrine and/or autocrine manners in addition to endocrine manner. GHSR expression level was higher in hypothalamus, epencephalon and medulla oblongata, and moderate in multiple peripheral tissues including lung, kindey, stomach and oviduct, implicating that ghrelin/GHSR system may participate in the regulation of energy balance, food intake, water and mineral balance, gastrointestinal motility, gastric acid secretion and reproduction. During hibernation, the expression of ghrelin and GHSR in the brain was significantly increased, while ghrelin was significantly decreased in heart, liver, lung, stomach, pancreas and ovary, and GHSR was significantly decreased in heart, liver, spleen, lung, kindey, stomach, ovary and oviduct. These temporal changes in ghrelin and GHSR expression could facilitate the physiological adaption to the hibernation of Chinese alligator. Our study could provide basic data for further studies on the regulation of feeding, physiological metabolism and reproduction of Chinese alligator, which could also be useful for the improvement of artificial breeding of this endangered species.
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Affiliation(s)
- Xianxian Chen
- Key Laboratory for Conservation and Use of Important Biological Resources of Anhui Province, College of Life Sciences, Anhui Normal University, Wuhu, Anhui 241000, China
| | - Jicong Mi
- Key Laboratory for Conservation and Use of Important Biological Resources of Anhui Province, College of Life Sciences, Anhui Normal University, Wuhu, Anhui 241000, China
| | - Hongbin Huang
- Key Laboratory for Conservation and Use of Important Biological Resources of Anhui Province, College of Life Sciences, Anhui Normal University, Wuhu, Anhui 241000, China
| | - Jing Wang
- Key Laboratory for Conservation and Use of Important Biological Resources of Anhui Province, College of Life Sciences, Anhui Normal University, Wuhu, Anhui 241000, China
| | - Yu Wu
- Key Laboratory for Conservation and Use of Important Biological Resources of Anhui Province, College of Life Sciences, Anhui Normal University, Wuhu, Anhui 241000, China
| | - Xiaobing Wu
- Key Laboratory for Conservation and Use of Important Biological Resources of Anhui Province, College of Life Sciences, Anhui Normal University, Wuhu, Anhui 241000, China
| | - Shengzhou Zhang
- Key Laboratory for Conservation and Use of Important Biological Resources of Anhui Province, College of Life Sciences, Anhui Normal University, Wuhu, Anhui 241000, China.
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10
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Pavlidis ET, Pavlidis TE. Molecular factors, diagnosis and management of gastrointestinal tract neuroendocrine tumors: An update. World J Clin Cases 2022; 10:9573-9587. [PMID: 36186187 PMCID: PMC9516923 DOI: 10.12998/wjcc.v10.i27.9573] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2022] [Revised: 07/16/2022] [Accepted: 08/17/2022] [Indexed: 02/05/2023] Open
Abstract
The prevalence of gastrointestinal neuroendocrine tumors (GI-NETs) is increasing, and despite recent advances in their therapy, it remains inadequate in patients with advanced well-differentiated neuroendocrine tumors. These tumors present many challenges concerning the molecular basis and genomic profile, pathophysiology, clinicopathological features, histopathologic classification, diagnosis and treatment. There has been an ongoing debate on diagnostic criteria and clinical behavior, and various changes have been made over the last few years. Neuroendocrine carcinoma of the gastrointestinal system is a rare but highly malignant neoplasm that is genetically distinct from gastrointestinal system neuroendocrine tumors (NETs). The diagnosis and management have changed over the past decade. Emerging novel biomarkers and metabolic players in cancer cells are useful and promising new diagnostic tools. Progress in positron emission tomography-computerized tomography and scintigraphy with new radioactive agents (64Cu-DOTATATE or 68Ga-DOTATATE) replacing enough octreoscan, has improved further the current diagnostic imaging. Promising results provide targeted therapies with biological agents, new drugs, chemotherapy and immunotherapy. However, the role of surgery is important, since it is the cornerstone of management. Simultaneous resection of small bowel NETs with synchronous liver metastases is a surgical challenge. Endoscopy offers novel options not only for diagnosis but also for interventional management. The therapeutic option should be individualized based on current multidisciplinary information.
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Affiliation(s)
- Efstathios Theodoros Pavlidis
- Department of 2nd Surgical Propedeutic, Hippocration Hospital, Aristotle University of Thessaloniki, School of Medicine, Thessaloniki 54642, Greece
| | - Theodoros Efstathios Pavlidis
- Department of 2nd Surgical Propedeutic, Aristotle University of Thessaloniki, School of Medicine, Thessaloniki 54642, Greece
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Role of the Ghrelin System in Colorectal Cancer. Int J Mol Sci 2022; 23:ijms23105380. [PMID: 35628187 PMCID: PMC9141034 DOI: 10.3390/ijms23105380] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2022] [Revised: 05/06/2022] [Accepted: 05/10/2022] [Indexed: 02/06/2023] Open
Abstract
The ghrelin system contains several components (e.g., ghrelin with growing number of alternative peptides, growth hormone secretagogue receptors (GHS-Rs), and ghrelin-O-acyl-transferase (GOAT) and participates in regulation of a number of key processes of gastrointestinal (GI) tract cancer progression, including cell proliferation, migration, invasion, apoptosis, inflammation, and angiogenesis. However, its exact role in promoting or inhibiting cancer progression is still unclear. Colorectal cancer (CRC) is one of the most common human malignancies worldwide. Molecular studies suggest an autocrine/paracrine mechanism for the secretion of ghrelin in colorectal carcinogenesis and its contribution to its initial stages. However, the signalling pathways of CRC development involving the ghrelin system are poorly understood. Potential mechanisms of colon carcinogenesis involving components of the ghrelin system were previously described in an animal model and in in vitro studies. However, the diagnostic–prognostic role of serum ghrelin concentrations, tissue expression, or genetic changes of this system in various stages of CRC progression remains an open case. Thus, the aim of this study is to discuss the role of the ghrelin system in colon carcinogenesis, diagnostics and CRC prognostics, as well as the results of studies on the use of ghrelin and its analogues in the therapy of CRC-related syndromes (e.g., cachexia and sarcopenia).
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Wang D, Yang Y, Song Y, Fu S, He X, Wang B, Wang L, Chen X, Li X, Liu Y, Cao G. The Effect of Ghrelin on the Maturation of Sheep Oocytes and Early Embryonic Development In Vitro. Animals (Basel) 2022; 12:ani12091158. [PMID: 35565584 PMCID: PMC9100601 DOI: 10.3390/ani12091158] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2022] [Revised: 04/26/2022] [Accepted: 04/28/2022] [Indexed: 02/04/2023] Open
Abstract
Simple Summary Different gradients of ghrelin (0, 100, 200, and 300 ng/mL) were added to the IVM system of sheep oocytes to observe their changes, and 200 ng/mL ghrelin was found to be the optimal concentration. The RNA-seq analysis showed that the Cell cycle signaling pathway was enriched. The results suggest that adding ghrelin shortens the duration of IVM of sheep oocytes and hinders early embryonic development. Abstract In vitro maturation (IVM) of sheep oocytes and early embryonic development are of great scientific importance for the study of reproductive development in sheep. Ghrelin is an important hormone that regulates the secretion of the growth hormone (GH). In this study, different gradients of ghrelin (0, 100, 200, and 300 ng/mL) were added to the IVM system of sheep oocytes to observe their cell morphology, and Hosesth 33342 staining was used to determine the time taken for oocytes to reach different developmental stages. We found 200 ng/mL ghrelin to be the optimal concentration. The RNA-seq analysis showed that many signaling pathways were significantly altered by ghrelin. Cell cycle, Wnt, and oxidative phosphorylation were activated; the P53 was inhibited. These pathways together regulate the maturation of oocytes and early embryonic development in vitro. The effects of the addition of ghrelin were verified by the expression of GLUT1 in early embryonic development. The results suggest that adding ghrelin shortens the duration of the IVM of sheep oocytes and hinders early embryonic development. This study provides new insights into the effects of exogenous ghrelin on sheep oocyte maturation and early embryonic development in vitro.
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Affiliation(s)
- Daqing Wang
- Institute of Animal Husbandry, Inner Mongolia Academy of Agricultural and Animal Husbandry Sciences, Hohhot 010031, China; (D.W.); (Y.Y.); (S.F.); (X.H.); (B.W.); (L.W.); (X.C.)
- School of Veterinary Medicine, Inner Mongolia Agricultural University, Hohhot 010010, China
| | - Yanyan Yang
- Institute of Animal Husbandry, Inner Mongolia Academy of Agricultural and Animal Husbandry Sciences, Hohhot 010031, China; (D.W.); (Y.Y.); (S.F.); (X.H.); (B.W.); (L.W.); (X.C.)
| | - Yongli Song
- Research Center for Animal Genetic Resources of Mongolia Plateau, School of Life Sciences, Inner Mongolia University, Hohhot 010021, China;
| | - Shaoyin Fu
- Institute of Animal Husbandry, Inner Mongolia Academy of Agricultural and Animal Husbandry Sciences, Hohhot 010031, China; (D.W.); (Y.Y.); (S.F.); (X.H.); (B.W.); (L.W.); (X.C.)
| | - Xiaolong He
- Institute of Animal Husbandry, Inner Mongolia Academy of Agricultural and Animal Husbandry Sciences, Hohhot 010031, China; (D.W.); (Y.Y.); (S.F.); (X.H.); (B.W.); (L.W.); (X.C.)
| | - Biao Wang
- Institute of Animal Husbandry, Inner Mongolia Academy of Agricultural and Animal Husbandry Sciences, Hohhot 010031, China; (D.W.); (Y.Y.); (S.F.); (X.H.); (B.W.); (L.W.); (X.C.)
| | - Liwei Wang
- Institute of Animal Husbandry, Inner Mongolia Academy of Agricultural and Animal Husbandry Sciences, Hohhot 010031, China; (D.W.); (Y.Y.); (S.F.); (X.H.); (B.W.); (L.W.); (X.C.)
| | - Xin Chen
- Institute of Animal Husbandry, Inner Mongolia Academy of Agricultural and Animal Husbandry Sciences, Hohhot 010031, China; (D.W.); (Y.Y.); (S.F.); (X.H.); (B.W.); (L.W.); (X.C.)
| | - Xihe Li
- Research Center for Animal Genetic Resources of Mongolia Plateau, School of Life Sciences, Inner Mongolia University, Hohhot 010021, China;
- Correspondence: (X.L.); (Y.L.); (G.C.)
| | - Yongbin Liu
- The State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, School of Life Sciences, Inner Mongolia University, Hohhot 010021, China
- Correspondence: (X.L.); (Y.L.); (G.C.)
| | - Guifang Cao
- School of Veterinary Medicine, Inner Mongolia Agricultural University, Hohhot 010010, China
- Correspondence: (X.L.); (Y.L.); (G.C.)
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Stojsavljevic-Shapeski S, Virovic-Jukic L, Tomas D, Duvnjak M, Tomasic V, Hrabar D, Kralj D, Budimir I, Barsic N, Ljubicic N. Expression of adipokine ghrelin and ghrelin receptor in human colorectal adenoma and correlation with the grade of dysplasia. World J Gastrointest Surg 2021; 13:1708-1720. [PMID: 35070075 PMCID: PMC8727187 DOI: 10.4240/wjgs.v13.i12.1708] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2021] [Revised: 08/20/2021] [Accepted: 11/03/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Ghrelin is an adipokine that plays an important role in energy balance. Expression of ghrelin and ghrelin receptor has been investigated in different tissues and tumors. Studies regarding expression of ghrelin and ghrelin receptor in colorectal tumors are scarce and no data on expression of ghrelin and its receptor in colorectal adenomas has been published. Ghrelin and ghrelin receptor were highly expressed in colon carcinoma cells while expression was decreased in less differentiated tumors, presuming that ghrelin might be important in early phases of tumorigenesis. AIM To investigate the expression of ghrelin and ghrelin receptor in human colorectal adenomas and adjacent colorectal tissue. METHODS In this prospective study (conducted from June 2015 until May 2019) we included 92 patients (64 male and 28 female) who underwent polypectomy for colorectal adenomas in the Department of Gastroenterology and Hepatology, "Sestre milosrdnice" Clinical Hospital Center in Zagreb, Croatia. After endoscopic removal of colorectal adenoma, an additional sample of colon mucosa in the proximity of the adenoma was collected for pathohistological analysis. Adenomas were graded according to the stage of dysplasia, and ghrelin and ghrelin receptor expression were determined immunohistochemically in both adenoma and adjacent colon tissue using the polyclonal antibody for ghrelin (ab150514, ABCAM Inc, Cambridge, United States) and ghrelin receptor (ab48285, ABCAM Inc, Cambridge, United States). Categorical and nominal variables were described through frequencies and proportions and the difference between specific groups were analyzed with Fisher's and Fisher-Freeman-Halton's method respectively. Spearman's rank correlation coefficient was determined for correlation of expression of ghrelin and ghrelin receptor in adenoma and adjacent colon tissue with the grade of adenoma dysplasia. RESULTS Among 92 patients with colorectal adenoma 43 had adenomas with high-grade dysplasia (46.7%). High expression of ghrelin was 7 times more common in high-grade adenoma compared to low-grade adenomas (13.95% to 2.04%, P = 0.048), while the expression of ghrelin in adjacent colon tissue was low. We found no correlation between ghrelin receptor expression in adenoma and adjacent colon tissue and the grade of colorectal adenoma dysplasia. The most significant correlation was found between ghrelin and ghrelin receptor expression in adenomas with high-grade dysplasia (rho = 0.519, P < 0.001). CONCLUSION Ghrelin and ghrelin receptor are expressed in colorectal adenoma and adjacent tissue with ghrelin expression being more pronounced in high grade dysplasia as a possible consequence of increased local synthesis.
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Affiliation(s)
- Sanja Stojsavljevic-Shapeski
- Division of Gastroenterology, Department of Internal Medicine, «Sestre Milosrdnice» University Hospital Center, Zagreb 10000, Croatia
| | - Lucija Virovic-Jukic
- Division of Gastroenterology, Department of Internal Medicine, «Sestre Milosrdnice» University Hospital Center, Zagreb 10000, Croatia
- Department of Internal Medicine, School of Medicine, University of Zagreb, Zagreb 10000, Croatia
| | - Davor Tomas
- Ljudevit Jurak Department of Pathology, «Sestre Milosrdnice» University Hospital Center, Zagreb 10000, Croatia
- Department of Pathology, School of Medicine, University of Zagreb, Zagreb 10000, Croatia
| | - Marko Duvnjak
- Department of Internal Medicine, School of Medicine, University of Zagreb, Zagreb 10000, Croatia
| | - Vedran Tomasic
- Division of Gastroenterology, Department of Internal Medicine, «Sestre Milosrdnice» University Hospital Center, Zagreb 10000, Croatia
| | - Davor Hrabar
- Division of Gastroenterology, Department of Internal Medicine, «Sestre Milosrdnice» University Hospital Center, Zagreb 10000, Croatia
- Department of Internal Medicine, School of Medicine, University of Zagreb, Zagreb 10000, Croatia
| | - Dominik Kralj
- Division of Gastroenterology, Department of Internal Medicine, «Sestre Milosrdnice» University Hospital Center, Zagreb 10000, Croatia
| | - Ivan Budimir
- Division of Gastroenterology, Department of Internal Medicine, «Sestre Milosrdnice» University Hospital Center, Zagreb 10000, Croatia
| | - Neven Barsic
- Department of Internal Medicine, School of Medicine, University of Zagreb, Zagreb 10000, Croatia
- Division of Gastroenterology, Department of Internal Medicine, «Sestre Milosrdnice» University Hospital Center, Zagreb 10000, Croatia
| | - Neven Ljubicic
- Division of Gastroenterology, Department of Internal Medicine, «Sestre Milosrdnice» University Hospital Center, Zagreb 10000, Croatia
- Department of Internal Medicine, School of Medicine, University of Zagreb, Zagreb 10000, Croatia
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Batty MJ, Chabrier G, Sheridan A, Gage MC. Metabolic Hormones Modulate Macrophage Inflammatory Responses. Cancers (Basel) 2021; 13:cancers13184661. [PMID: 34572888 PMCID: PMC8467249 DOI: 10.3390/cancers13184661] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2021] [Revised: 08/31/2021] [Accepted: 09/13/2021] [Indexed: 12/17/2022] Open
Abstract
Simple Summary Macrophages are a type of immune cell which play an important role in the development of cancer. Obesity increases the risk of cancer and obesity also causes disruption to the normal levels of hormones that are produced to coordinate metabolism. Recent research now shows that these metabolic hormones also play important roles in macrophage immune responses and so through macrophages, disrupted metabolic hormone levels may promote cancer. This review article aims to highlight and summarise these recent findings so that the scientific community may better understand how important this new area of research is, and how these findings can be capitalised on for future scientific studies. Abstract Macrophages are phagocytotic leukocytes that play an important role in the innate immune response and have established roles in metabolic diseases and cancer progression. Increased adiposity in obese individuals leads to dysregulation of many hormones including those whose functions are to coordinate metabolism. Recent evidence suggests additional roles of these metabolic hormones in modulating macrophage inflammatory responses. In this review, we highlight key metabolic hormones and summarise their influence on the inflammatory response of macrophages and consider how, in turn, these hormones may influence the development of different cancer types through the modulation of macrophage functions.
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