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Xu ZH, Xiong CW, Miao KS, Yu ZT, Zhang JJ, Yu CL, Huang Y, Zhou XD. Adipokines regulate mesenchymal stem cell osteogenic differentiation. World J Stem Cells 2023; 15:502-513. [PMID: 37424950 PMCID: PMC10324509 DOI: 10.4252/wjsc.v15.i6.502] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/14/2022] [Revised: 02/26/2023] [Accepted: 04/24/2023] [Indexed: 06/26/2023] Open
Abstract
Mesenchymal stem cells (MSCs) can differentiate into various tissue cell types including bone, adipose, cartilage, and muscle. Among those, osteogenic differentiation of MSCs has been widely explored in many bone tissue engineering studies. Moreover, the conditions and methods of inducing osteogenic differentiation of MSCs are continuously advancing. Recently, with the gradual recognition of adipokines, the research on their involvement in different pathophysiological processes of the body is also deepening including lipid metabolism, inflammation, immune regulation, energy disorders, and bone homeostasis. At the same time, the role of adipokines in the osteogenic differentiation of MSCs has been gradually described more completely. Therefore, this paper reviewed the evidence of the role of adipokines in the osteogenic differentiation of MSCs, emphasizing bone formation and bone regeneration.
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Affiliation(s)
- Zhong-Hua Xu
- Department of Orthopedics, Jintan Hospital Affiliated to Jiangsu University, Changzhou 213200, Jiangsu Province, China
| | - Chen-Wei Xiong
- Department of Orthopedics, The Affiliated Changzhou Second People’s Hospital of Nanjing Medical University, Changzhou 213000, Jiangsu Province, China
- Changzhou Medical Center, Nanjing Medical University, Changzhou 213000, Jiangsu Province, China
| | - Kai-Song Miao
- Department of Orthopedics, The Affiliated Changzhou Second People’s Hospital of Nanjing Medical University, Changzhou 213000, Jiangsu Province, China
- Changzhou Medical Center, Nanjing Medical University, Changzhou 213000, Jiangsu Province, China
| | - Zhen-Tang Yu
- Department of Orthopedics, The Affiliated Changzhou Second People’s Hospital of Nanjing Medical University, Changzhou 213000, Jiangsu Province, China
- Changzhou Medical Center, Nanjing Medical University, Changzhou 213000, Jiangsu Province, China
| | - Jun-Jie Zhang
- Department of Orthopedics, The Affiliated Changzhou Second People’s Hospital of Nanjing Medical University, Changzhou 213000, Jiangsu Province, China
- Changzhou Medical Center, Nanjing Medical University, Changzhou 213000, Jiangsu Province, China
| | - Chang-Lin Yu
- Department of Orthopedics, The Affiliated Changzhou Second People’s Hospital of Nanjing Medical University, Changzhou 213000, Jiangsu Province, China
- Changzhou Medical Center, Nanjing Medical University, Changzhou 213000, Jiangsu Province, China
| | - Yong Huang
- Department of Orthopedics, The Affiliated Changzhou Second People’s Hospital of Nanjing Medical University, Changzhou 213000, Jiangsu Province, China
- Changzhou Medical Center, Nanjing Medical University, Changzhou 213000, Jiangsu Province, China
| | - Xin-Die Zhou
- Department of Orthopedics, The Affiliated Changzhou Second People’s Hospital of Nanjing Medical University, Changzhou 213000, Jiangsu Province, China
- Changzhou Medical Center, Nanjing Medical University, Changzhou 213000, Jiangsu Province, China
- Department of Orthopedics, Gonghe County Hospital of Traditional Chinese Medicine, Hainan Tibetan Autonomous Prefecture 811800, Qinghai Province, China
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Schaper SJ, Wölk E, Hofmann T, Friedrich T, Römer M, de Punder K, Rose M, Stengel A. NUCB2/nesfatin-1 in the acute stress response of obese women with high and low anxiety. Psychoneuroendocrinology 2023; 155:106325. [PMID: 37385089 DOI: 10.1016/j.psyneuen.2023.106325] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2023] [Revised: 06/20/2023] [Accepted: 06/21/2023] [Indexed: 07/01/2023]
Abstract
NUCB2/nesfatin-1 is an anorexigenic peptide hormone first known for its effects on energy homeostasis. More recently, a growing evidence suggests a role of NUCB2/nesfatin-1 in emotion regulation, particularly in the modulation of anxiety, depression and emotional stress response. Since stress-related mood disorders are often comorbid with obesity, we investigated the effect of acute psychosocial stress on circulating NUCB2/nesfatin-1 in obese women and normal-weight controls and its association with symptoms of anxiety. Forty women, 20 obese and 20 normal-weight controls, (aged between 27 and 46 years) were exposed to the Trier Social Stress Test (TSST). We assessed changes of plasma NUCB2/nesfatin-1, salivary cortisol, heart rate and subjective emotional state. Symptoms of anxiety (GAD-7), depressiveness (PHQ-9), perceived stress (PSQ-20), disordered eating (EDE-Q, EDI-2) and health-related quality of life (SF-8) were measured psychometrically. Obese women were further subdivided in a high and low anxiety group. Women with obesity displayed higher psychopathology compared to normal-weight controls. The TSST induced a biological and psychological stress response in both groups (p < 0.001). In normal-weight controls NUCB2/nesfatin-1 increased in response to stress (p = 0.011) and decreased during recovery (p < 0.050), while in obese women only the decrease during recovery was significant (p = 0.002). Obese women with high anxiety displayed higher NUCB2/nesfatin-1 levels than those in the low anxiety group (TSST: +34 %, p = 0.008; control condition: +52 %, p = 0.013). Our data substantiate the involvement of NUCB2/nesfatin-1 in the modulation of stress and anxiety. It remains unclear whether the attenuated stress response in obese subjects is due to metabolic changes or mental comorbidity.
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Affiliation(s)
- Selina Johanna Schaper
- Charité Center for Internal Medicine and Dermatology, Department for Psychosomatic Medicine, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 12203 Berlin, Germany
| | - Ellen Wölk
- Charité Center for Internal Medicine and Dermatology, Department for Psychosomatic Medicine, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 12203 Berlin, Germany
| | - Tobias Hofmann
- Charité Center for Internal Medicine and Dermatology, Department for Psychosomatic Medicine, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 12203 Berlin, Germany; Department of Psychosomatic Medicine and Psychotherapy, DRK Kliniken Berlin Wiegmann Klinik, Berlin, Germany
| | - Tiemo Friedrich
- Charité Center for Internal Medicine and Dermatology, Department for Psychosomatic Medicine, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 12203 Berlin, Germany
| | - Marthe Römer
- Charité Center for Internal Medicine and Dermatology, Department for Psychosomatic Medicine, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 12203 Berlin, Germany
| | - Karin de Punder
- Institute of Medical Psychology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany; Institute of Psychology, Department of Clinical Psychology-II, University of Innsbruck, Austria
| | - Matthias Rose
- Charité Center for Internal Medicine and Dermatology, Department for Psychosomatic Medicine, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 12203 Berlin, Germany; Department of Quantitative Health Sciences, University of Massachusetts Medical School, Worcester, MA, USA
| | - Andreas Stengel
- Charité Center for Internal Medicine and Dermatology, Department for Psychosomatic Medicine, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 12203 Berlin, Germany; Department of Psychosomatic Medicine and Psychotherapy, Medical University Hospital Tübingen, 72076 Tübingen, Germany.
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NUCB2/Nesfatin-1 Regulation of Chronic Visceral Hyperalgesia. Appl Bionics Biomech 2022; 2022:4079533. [PMID: 35847627 PMCID: PMC9286992 DOI: 10.1155/2022/4079533] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2022] [Revised: 06/09/2022] [Accepted: 06/25/2022] [Indexed: 12/04/2022] Open
Abstract
Objective We previously described that different concentration Nucleobindin-2 (NUCB2)/Nesfatin-1 gradients differently regulated visceral hypersensitivity in irritable bowel syndrome. Therefore, this study is aimed at evaluating the effect of NUCB2/Nesfatin-1 on model rats with chronic visceral hyperalgesia. Methods Neonatal and mature Sprague-Dawley rats were randomly divided into the healthy control and chronic visceral hyperalgesia model groups. The model was built by combining maternal separation with the acetic acid enema. The models were identified by the distension volume threshold to reach abdominal withdraw reflex (AWR) score = 3, histological staining, and myeloperoxidase (MPO) detection. The visceral sensitivity to chronic visceral hyperalgesia was then evaluated. Result Rats in the model group responded more strongly to pulling stimulation than healthy controls; the distension volume threshold causing AWR3 response in model rats was lower than the control group before NUCB2/Nesfatin-1 intervention. After intervention, the distension volume threshold was significantly lower in the NUCB2/Nesfatin-1 central intervention group than in the NUCB2/Nesfatin-1 peripheral intervention group, and the peak value of external oblique muscle electrical activity was significantly higher. Additionally, compared with the male intervention group, in the female intervention group, the volume threshold was significantly lower and the peak value was higher. Conclusion NUCB2/Nesfatin-1 could regulate visceral sensitivity in chronic visceral hyperalgesia model rats; its regulatory effect correlated with the type of NUCB2/Nesfatin-1 intervention approaches (central or peripheral) and sex (male or female).
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Pham V, Pemberton JG, Chang JP, Blanco AM, Nasri A, Unniappan S. Nesfatin-1 stimulates the hypothalamus-pituitary-interrenal axis hormones in goldfish. Am J Physiol Regul Integr Comp Physiol 2021; 321:R603-R613. [PMID: 34405712 DOI: 10.1152/ajpregu.00063.2021] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Stress in vertebrates is mediated by the hypothalamus-pituitary-adrenal (in mammals)/interrenal (in fish) (HPA/I) axis, which produces the corticotropin-releasing factor (CRF), adrenocorticotropic hormone (ACTH), and corticosteroids, respectively. Nesfatin-1, a novel anorexigenic peptide encoded in the precursor nucleobindin-2 (NUCB2), is increasingly acknowledged as a peptide that influences the stress axis in mammals. The primary aim of this study was to characterize the putative effects of nesfatin-1 on the fish HPI axis, using goldfish (Carassius auratus) as an animal model. Our results demonstrated that nucb2/nesfatin-1 transcript abundance was detected in the HPI tissues of goldfish, with most abundant expression in the pituitary. NUCB2/nesfatin-1-like immunoreactivity was found in the goldfish hypothalamus, pituitary, and interrenal cells of the head kidney. GPCR12, a putative receptor for nesfatin-1, was also detected in the pituitary and interrenal cells. NUCB2/nesfatin-1-like immunoreactivity was observed in ACTH-expressing pituitary corticotrophs. Acute netting and restraint stress upregulated nucb2/nesfatin-1 mRNA levels in the forebrain, hypothalamus, and pituitary, as well as crf and crf-r1 expression in the forebrain and hypothalamus. Intraperitoneal and intracerebroventricular administration of nesfatin-1 increased cortisol release and hypothalamic crf mRNA levels, respectively. Finally, we found that nesfatin-1 significantly stimulated ACTH secretion from dispersed pituitary cells in vitro. Collectively, our data provide the first evidence showing that nesfatin-1 is a stress responsive peptide, which modulates the stress axis hormones in fish.
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Affiliation(s)
- Vi Pham
- Laboratory of Integrative Neuroendocrinology, Department of Veterinary Biomedical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada
| | - Joshua G Pemberton
- Department of Biological Sciences, University of Alberta, Edmonton, Alberta, Canada
| | - John P Chang
- Department of Biological Sciences, University of Alberta, Edmonton, Alberta, Canada
| | - Ayelen Melisa Blanco
- Laboratory of Integrative Neuroendocrinology, Department of Veterinary Biomedical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada
| | - Atefeh Nasri
- Laboratory of Integrative Neuroendocrinology, Department of Veterinary Biomedical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada
| | - Suraj Unniappan
- Laboratory of Integrative Neuroendocrinology, Department of Veterinary Biomedical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada
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Luo JJ, Wen FJ, Qiu D, Wang SZ. Nesfatin-1 in lipid metabolism and lipid-related diseases. Clin Chim Acta 2021; 522:23-30. [PMID: 34389280 DOI: 10.1016/j.cca.2021.08.005] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2021] [Revised: 07/28/2021] [Accepted: 08/07/2021] [Indexed: 12/13/2022]
Abstract
Nesfatin-1, an anorexic neuropeptide discovered in 2006, is widely distributed in the central nervous system and peripheral tissues. It has been shown to be involved in the regulation of food intake and lipid metabolism, inhibiting fat accumulation, accelerating lipid decomposition, and in general, inhibiting the development of lipid-related diseases, such as obesity and metabolic syndrome. Potential mechanisms of Nesfatin-1 action in lipid metabolism and lipid-related diseases will be discussed as well as its role as a biomarker in cardiovascular disease. This review expected to provide a new strategy for the diagnosis and prevention of clinically related diseases.
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Affiliation(s)
- Jing-Jing Luo
- Institute of Pharmacy and Pharmacology, School of Pharmaceutical Sciences, University of South China, Hengyang 421001, China; Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang 421001, China
| | - Feng-Jiao Wen
- Institute of Cardiovascular Disease, Key Laboratory for Arteriosclerology of Hunan Province, Hunan International Scientific and Technological Cooperation Base of Arteriosclerotic Disease, Department of Cell Biology and Geneties, University of South China, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Hengyang Medical College, University of South China, Hengyang, Hunan 421001, China
| | - Dan Qiu
- Institute of Pharmacy and Pharmacology, School of Pharmaceutical Sciences, University of South China, Hengyang 421001, China; Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang 421001, China
| | - Shu-Zhi Wang
- Institute of Pharmacy and Pharmacology, School of Pharmaceutical Sciences, University of South China, Hengyang 421001, China; Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang 421001, China.
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Xu D, Yu Y, Xu Y, Ge J. Plasma Nesfatin-1: Potential Predictor and Diagnostic Biomarker for Cognitive Dysfunction in T2DM Patient. Diabetes Metab Syndr Obes 2021; 14:3555-3566. [PMID: 34408457 PMCID: PMC8364362 DOI: 10.2147/dmso.s323009] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2021] [Accepted: 07/30/2021] [Indexed: 12/14/2022] Open
Abstract
PURPOSE Nesfatin-1 plays a crucial role in glucose metabolism and cognitive function. This study aimed to investigate the correlation between plasma nesfatin-1 levels and clinical indicators and cognitive function in patients with type 2 diabetes mellitus (T2DM). METHODS Demographic and medical history data, physical examination, and biochemical test results of 132 T2DM patients were collected. The plasma concentrations of nesfatin-1, C-reactive protein (CRP), interleukin-6 (IL-6), soluble triggering receptors expressed on myeloid cells 1 (sTREM1), and sTREM2 in T2DM patients were measured. Cognitive function was evaluated using the Behavior Rating Inventory of Executive Function-Adult (BRIEF-A). The patients were divided into two groups: a low-nesfatin-1 group (n = 75) and a high-nesfatin-1 group (n = 57) based on a plasma nesfatin-1 concentration less than or above the 50th percentile value of all the samples. RESULTS The results showed that plasma HbA1c levels were positively correlated with CRP, IL-6, sTREM1, and sTREM2 levels in patients with T2DM (P < 0.05). Plasma nesfatin-1 concentrations were positively associated with diabetes-related biochemical indicators including glycated haemoglobin (HbA1c), insulin, and homeostatic model assessment of insulin resistance (HOMA-IR), and inflammation-related indicators including CRP, IL-6, sTREM1, and sTREM2 among patients with T2DM (P < 0.05). Moreover, T2DM patients with high nesfatin-1 levels showed higher HbA1c and fasting plasma glucose (FPG) levels (P < 0.05). Furthermore, T2DM patients with high nesfatin-1 levels also showed higher BRIEF-A scores (P = 0.01). Additionally, T2DM patients with high total scores of BRIEF-A (scores > 50th percentile) could be identified with a sensitivity of 59.1% and a specificity of 72.7% by nesfatin-1. CONCLUSION These findings indicate that plasma nesfatin-1 might be involved in the T2DM-associated comorbidities and the development of cognitive dysfunction, and the mechanism underlying this involvement is related to the imbalance in the expression of CRP, IL-6, sTREM1, and sTREM2 levels.
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Affiliation(s)
- Dandan Xu
- School of Pharmacy, Anhui Medical University, Hefei, People’s Republic of China
- Anhui Province Key Laboratory of Major Autoimmune Diseases, Anhui Institute of Innovative Drugs, Hefei, People’s Republic of China
- The Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anhui Medical University, Hefei, People’s Republic of China
| | - Yue Yu
- School of Pharmacy, Anhui Medical University, Hefei, People’s Republic of China
- Department of Pharmacy, The Fourth Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China
| | - Yayun Xu
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, People’s Republic of China
| | - Jinfang Ge
- School of Pharmacy, Anhui Medical University, Hefei, People’s Republic of China
- Anhui Province Key Laboratory of Major Autoimmune Diseases, Anhui Institute of Innovative Drugs, Hefei, People’s Republic of China
- The Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anhui Medical University, Hefei, People’s Republic of China
- Correspondence: Jinfang Ge School of Pharmacy, Anhui Medical University, 81 Mei-Shan Road, Hefei, Anhui, 230032, People’s Republic of ChinaTel +86 551 65172131Fax +86 551 65161115 Email
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Xu Y, Chen F. Antioxidant, Anti-Inflammatory and Anti-Apoptotic Activities of Nesfatin-1: A Review. J Inflamm Res 2020; 13:607-617. [PMID: 33061526 PMCID: PMC7532075 DOI: 10.2147/jir.s273446] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2020] [Accepted: 08/29/2020] [Indexed: 12/12/2022] Open
Abstract
Nesfatin-1, a newly identified energy-regulating peptide, is widely expressed in the central and peripheral tissues, and has a variety of physiological activities. A large number of recent studies have shown that nesfatin-1 exhibits antioxidant, anti-inflammatory, and anti-apoptotic properties and is involved in the occurrence and progression of various diseases. This review summarizes current data focusing on the therapeutic effects of nesfatin-1 under different pathophysiological conditions and the mechanisms underlying its antioxidant, anti-inflammatory, and anti-apoptotic activities.
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Affiliation(s)
- Yayun Xu
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, People's Republic of China.,The Key Laboratory of Major Autoimmune Diseases of Anhui Province, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei, People's Republic of China.,The Key Laboratory of Anti-Inflammatory and Immune Medicines, Ministry of Education, Hefei, People's Republic of China
| | - Feihu Chen
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, People's Republic of China.,The Key Laboratory of Major Autoimmune Diseases of Anhui Province, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei, People's Republic of China.,The Key Laboratory of Anti-Inflammatory and Immune Medicines, Ministry of Education, Hefei, People's Republic of China
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Liu QJ, Lv JX, Liu J, Zhang XB, Wang LB. Nucleobindin-2 Promotes the Growth and Invasion of Glioblastoma. Cancer Biother Radiopharm 2020; 34:581-588. [PMID: 31697592 DOI: 10.1089/cbr.2019.2829] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
Background: Glioblastoma is one of the most malignant tumors in the brain with high mortality. In recent years, immunotherapy and targeted therapy show great prospects in the treatments for glioblastoma, whereas more effective therapeutic targets are still urgently needed to be developed. Nucleobindin-2 (NUCB2) is the precursor protein of nesfatin-1, which have a variety of metabolic functions, such as food intake and temperature regulation. In recent years, the potential link between NUCB2 and the development of multiple cancer was gradually revealed; however, the effects of NUCB2 on the progression of glioblastoma are still unclear. Methods: Immunohistochemical assays were performed to explore the NUCB2 expression levels in 94 samples of glioblastoma and corresponding nontumor tissues; patients were divided into NUCB2 high expression group and low expression group. Clinical analysis related to the clinical features, the potential link between NUCB2 expression levels, and clinical features were analyzed; the effects of NUCB2 on cell proliferation and invasion of glioblastoma were detected through colony formation and MTT assay, and transwell assay respectively. The possible effects of NUCB2 on tumor growth and metastasis were measured in mice. Results: In this study, we demonstrated that NUCB2 over-expression was correlated with the high degree of recurrence of patients with glioblastoma. Further, we also revealed that NUCB2 promoted cell proliferation and invasion of glioblastoma in vitro and promoted the growth and metastasis of glioblastoma in mice. Conclusion: This study provided evidence that NUCB2 might be a novel therapeutic target of glioblastoma.
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Affiliation(s)
- Qing-Jun Liu
- Department of Neurosurgery, Tianjin Huanhu Hospital, Tianjin, China
| | - Jia-Xi Lv
- Department of Neurosurgery, The Second People's Hospital of Guilin, Guilin, China
| | - Jun Liu
- Department of Neurosurgery, Tianjin Huanhu Hospital, Tianjin, China
| | - Xue-Bin Zhang
- Department of Pathology, Tianjin Huanhu Hospital, Tianjin, China
| | - Lei-Bo Wang
- Department of Neurosurgery, Tianjin Huanhu Hospital, Tianjin, China
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Tai KY, Wong K, Aghakhanian F, Parhar IS, Dhaliwal J, Ayub Q. Selected neuropeptide genes show genetic differentiation between Africans and non-Africans. BMC Genet 2020; 21:31. [PMID: 32171244 PMCID: PMC7071772 DOI: 10.1186/s12863-020-0835-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2019] [Accepted: 02/28/2020] [Indexed: 11/10/2022] Open
Abstract
Background Publicly available genome data provides valuable information on the genetic variation patterns across different modern human populations. Neuropeptide genes are crucial to the nervous, immune, endocrine system, and physiological homeostasis as they play an essential role in communicating information in neuronal functions. It remains unclear how evolutionary forces, such as natural selection and random genetic drift, have affected neuropeptide genes among human populations. To date, there are over 100 known human neuropeptides from the over 1000 predicted peptides encoded in the genome. The purpose of this study is to analyze and explore the genetic variation in continental human populations across all known neuropeptide genes by examining highly differentiated SNPs between African and non-African populations. Results We identified a total of 644,225 SNPs in 131 neuropeptide genes in 6 worldwide population groups from a public database. Of these, 5163 SNPs that had ΔDAF |(African - non-African)| ≥ 0.20 were identified and fully annotated. A total of 20 outlier SNPs that included 19 missense SNPs with a moderate impact and one stop lost SNP with high impact, were identified in 16 neuropeptide genes. Our results indicate that an overall strong population differentiation was observed in the non-African populations that had a higher derived allele frequency for 15/20 of those SNPs. Highly differentiated SNPs in four genes were particularly striking: NPPA (rs5065) with high impact stop lost variant; CHGB (rs6085324, rs236150, rs236152, rs742710 and rs742711) with multiple moderate impact missense variants; IGF2 (rs10770125) and INS (rs3842753) with moderate impact missense variants that are in linkage disequilibrium. Phenotype and disease associations of these differentiated SNPs indicated their association with hypertension and diabetes and highlighted the pleiotropic effects of these neuropeptides and their role in maintaining physiological homeostasis in humans. Conclusions We compiled a list of 131 human neuropeptide genes from multiple databases and literature survey. We detect significant population differentiation in the derived allele frequencies of variants in several neuropeptide genes in African and non-African populations. The results highlights SNPs in these genes that may also contribute to population disparities in prevalence of diseases such as hypertension and diabetes.
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Affiliation(s)
- Kah Yee Tai
- School of Information Technology, Monash University Malaysia, 47500, Bandar Sunway, Selangor Darul Ehsan, Malaysia
| | - KokSheik Wong
- School of Information Technology, Monash University Malaysia, 47500, Bandar Sunway, Selangor Darul Ehsan, Malaysia
| | - Farhang Aghakhanian
- Monash University Malaysia Genomics Facility, 47500, Bandar Sunway, Selangor Darul Ehsan, Malaysia
| | - Ishwar S Parhar
- Jeffrey Cheah School of Medicine and Health Sciences, Brain Research Institute, Monash University Malaysia, 47500, Bandar Sunway, Selangor Darul Ehsan, Malaysia
| | - Jasbir Dhaliwal
- School of Information Technology, Monash University Malaysia, 47500, Bandar Sunway, Selangor Darul Ehsan, Malaysia.
| | - Qasim Ayub
- Monash University Malaysia Genomics Facility, 47500, Bandar Sunway, Selangor Darul Ehsan, Malaysia.,School of Science, Monash University Malaysia, 47500, Bandar Sunway, Selangor Darul Ehsan, Malaysia
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Bülbül M, Travagli RA. Novel transmitters in brain stem vagal neurocircuitry: new players on the pitch. Am J Physiol Gastrointest Liver Physiol 2018; 315:G20-G26. [PMID: 29597355 PMCID: PMC6109706 DOI: 10.1152/ajpgi.00059.2018] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
The last few decades have seen a major increase in the number of neurotransmitters and neuropeptides recognized as playing a role in brain stem neurocircuits, including those involved in homeostatic functions such as stress responsiveness, gastrointestinal motility, feeding, and/or arousal/wakefulness. This minireview will focus on the known physiological role of three of these novel neuropeptides, i.e., apelin, nesfatin-1, and neuropeptide-S, with a special emphasis on their hypothetical roles in vagal signaling related to gastrointestinal motor functions.
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Affiliation(s)
- Mehmet Bülbül
- 1Faculty of Medicine, Department of Physiology, Akdeniz UniversityAntalya, Turkey
| | - R. Alberto Travagli
- 2Department of Neural and Behavioral Neurosciences, Pennsylvania State University College of Medicine, Hershey, Pennsylvania
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Nesfatin-1 in the dorsal raphe nucleus influences visceral sensitivity via 5-HT neurons in male maternally separated rats. Sci Rep 2018; 8:9334. [PMID: 29921870 PMCID: PMC6008476 DOI: 10.1038/s41598-018-27592-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2018] [Accepted: 06/04/2018] [Indexed: 12/19/2022] Open
Abstract
Nesfatin-1, a satiety molecule processed from nucleobindin2 (NUCB2), is implicated in visceral hypersensitivity in rats and colocalized with 5-hydroxytryptamine (5-HT) in the dorsal raphe nucleus (DRN). Maternal separation (MS) in rats contributes to visceral hypersensitivity via elevated expression of 5-HT in the DRN. Intracerebroventricular injection of nesfatin-1 activates DRN 5-HT neurons. In this study, A model of visceral hypersensitivity was developed by subjecting rats to MS. Colorectal distension was used to detect visceral sensitivity, which was evaluated by abdominal withdrawal reflex (AWR) scores and electromyogram (EMG) magnitude. MS rats exhibited higher AWR scores and EMG magnitude compared with controls. The numbers of nesfatin-1- and tryptophan hydroxylase (TPH, the rate-limiting enzyme for 5-HT synthesis)-positive cells in the DRN were significantly elevated accordingly. Visceral hypersensitivity was significantly alleviated in MS rats treated with intra-DRN administration of anti-nesfatin-1/NUCB2, accompanied by decreased expression of 5-HT and TPH in the DRN, compared with the vehicle-treated group. In contrast, intra-DRN administration of nesfatin-1 into normal adult rats induced visceral hypersensitivity, which correlated with elevated expression of 5-HT and TPH in the DRN. In conclusion, Nesfatin-1 has critical effects on visceral hypersensitivity; the underlying mechanisms might be related to the activation of DRN 5-HT neurons.
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Ozcan ATD, Altin CB, Erdogan S, Ergin M, Çiftçi A, Kara H, Aksoy SM, But A. The effects of Desflurane and Sevoflurane on Nesfatin-1 levels in laparoscopic Cholecystectomy: a randomized controlled trial. BMC Anesthesiol 2018; 18:23. [PMID: 29452603 PMCID: PMC5815222 DOI: 10.1186/s12871-018-0484-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2017] [Accepted: 01/25/2018] [Indexed: 11/10/2022] Open
Abstract
Background Nesfatin-1 is involved in cardiovascular regulation, stress-related responses. The objective of this study is to investigate the impact of volatile anesthetics on Nesfatin-1 levels. Method Fourty-two patients aged 30–65 years with the American Society Anesthesiology (ASA) Class I-II who were scheduled for laparoscopic cholecystectomy were included in the study Patients were randomized into two group; desflurane administered group (Group I, n = 21) and sevoflurane administered group (Group II, n = 21). For anesthesia maintenance, the patients received 6% desflurane or 2% sevoflurane in 40% O2 and 60% air. The patient’s heart rate (HR), mean, systolic and diastolic arterial pressures (MAP, SAP, DAP), peripheral O2 saturation (SpO2) were monitored and recorded before induction, after induction, after intubation, and during extubation. Blood samples were collected before induction (T1), and after extubation when aldrete score was 10 (T2). Results Demographic data were similar between the groups. The preoperative levels of nesfatin were similar in the two groups (p = 0.715). In desflurane group, post-operative nesfatin levels were similar compared to preoperative levels (p = 0.073). In sevoflurane group, post-operative nesfatin levels were similar (p = 0.131). The nesfatin levels (postoperative vs preoperative) were similar between the groups (p = 0.900). Conclusion In conclusion, this study results suggest that nesfatin-1 levels are not affected by the use of sevoflurane or desflurane in patients undergoing laparoscopic cholecystectomy. Trial registration Australian New Zealand Clinical Trials Registry, ACTRN12617001023347, retrospectively registered on 17 July 2017.
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Affiliation(s)
- A T D Ozcan
- Atatürk Training and Research Hospital, Anesthesiology and Reanimation Department, Atatürk Training and Research Hospital, Bilkent, Ankara, Turkey.
| | - C B Altin
- Yıldırım Beyazıt University Anesthesiology and Reanimation Department, Ankara, Turkey
| | - S Erdogan
- Atatürk Training and Research Hospital, Biochemistry Department, Ankara, Turkey
| | - M Ergin
- Atatürk Training and Research Hospital, Biochemistry Department, Ankara, Turkey
| | - A Çiftçi
- Atatürk Training and Research Hospital, Anesthesiology and Reanimation Department, Atatürk Training and Research Hospital, Bilkent, Ankara, Turkey
| | - H Kara
- Yıldırım Beyazıt University Pharmacology Department, Ankara, Turkey
| | - S M Aksoy
- Yıldırım Beyazıt University Anesthesiology and Reanimation Department, Ankara, Turkey
| | - A But
- Yıldırım Beyazıt University Anesthesiology and Reanimation Department, Ankara, Turkey
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Affiliation(s)
- Predrag Sikiric
- Medical Faculty, University of Zagreb Šalata 3, 10000 Zagreb Croatia
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St-Pierre DH, Martin J, Shimizu H, Tagaya Y, Tsuchiya T, Marceau S, Biertho L, Bastien M, Caron-Cantin SM, Simard S, Richard D, Cianflone K, Poirier P. Association between nesfatin-1 levels and metabolic improvements in severely obese patients who underwent biliopancreatic derivation with duodenal switch. Peptides 2016; 86:6-12. [PMID: 27681383 DOI: 10.1016/j.peptides.2016.09.014] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/24/2016] [Revised: 09/09/2016] [Accepted: 09/23/2016] [Indexed: 02/01/2023]
Abstract
CONTEXT Nesfatin-1 is a neuroendocrine peptide with potent anorexigenic activity in rodents. The potential role of nesfatin-1 on the regulation of energy balance, metabolic functions and inflammation is currently debated in obese humans. In the present study, nesfatin-1 fluctuations and their associations with metabolic factors were investigated in severely obese patients who underwent biliopancreatic diversion with duodenal switch (BPD/DS) and severely obese controls (SOC). BASIC PROCEDURES Sixty severely obese patients who underwent BPD/DS and 15 SOC (matched for BMI and age) were included in the study. Associations between nesfatin-1 levels and body composition, glucose metabolism, lipid profile as well as inflammatory markers were evaluated at baseline and over a post-surgery12-month (12M) period. MAIN FINDINGS Body weight was reduced at 6M and at 12M in BPD/DS patients (P<0.001). Nesfatin-1 levels were reduced at 6M (women: P<0.05) and at 12M (men and women; P<0.001) in BPD/DS patients. At baseline, nesfatin-1 levels negatively correlated with weight, fat (FM) and fat-free mass (FFM) in the whole population (combined BPD/DS and SOC patients). At 12M, nesfatin-1 concentrations positively correlated with weight, FM, fasting insulin, insulin resistance, total cholesterol, LDL-cholesterol, triglyceride and apoB values. At 12M, % changes in nesfatin-1 were positively associated with% changes in weight, FM, FFM, fasting insulin, insulin resistance, total cholesterol, LDL-cholesterol, apoB and C-reactive protein. CONCLUSION Nesfatin-1 levels decrease following BPD/DS-induced weight loss and are significantly associated with parameters of metabolic health.
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Affiliation(s)
- David H St-Pierre
- Centre de Recherche du CHU Sainte-Justine, Montréal, Québec, Canada; Département des Sciences de l'Activité Physique, Université du Québec à Montréal, Montréal, Québec, Canada
| | - Julie Martin
- Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Québec, Québec, Canada; Faculty of Pharmacy, Université Laval, Québec, Québec, Canada
| | - Hiroyuki Shimizu
- Faculty of Health Science, Kiryu University, Midori, Gunma, Japan
| | - Yuko Tagaya
- Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan
| | | | - Simon Marceau
- Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Québec, Québec, Canada; Faculty of Medicine, Université Laval, Québec, Québec, Canada
| | - Laurent Biertho
- Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Québec, Québec, Canada; Faculty of Medicine, Université Laval, Québec, Québec, Canada
| | - Marjorie Bastien
- Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Québec, Québec, Canada; Faculty of Pharmacy, Université Laval, Québec, Québec, Canada
| | - Sarah-Maude Caron-Cantin
- Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Québec, Québec, Canada; Faculty of Pharmacy, Université Laval, Québec, Québec, Canada
| | - Serge Simard
- Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Québec, Québec, Canada
| | - Denis Richard
- Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Québec, Québec, Canada; Faculty of Medicine, Université Laval, Québec, Québec, Canada
| | - Katherine Cianflone
- Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Québec, Québec, Canada; Faculty of Medicine, Université Laval, Québec, Québec, Canada
| | - Paul Poirier
- Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Québec, Québec, Canada; Faculty of Pharmacy, Université Laval, Québec, Québec, Canada.
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