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Cho SY, Eun HS, Kim J, Ko YD, Rou WS, Joo JS. The Solute Carrier Superfamily as Therapeutic Targets in Pancreatic Ductal Adenocarcinoma. Genes (Basel) 2025; 16:463. [PMID: 40282424 PMCID: PMC12027052 DOI: 10.3390/genes16040463] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2025] [Revised: 04/10/2025] [Accepted: 04/16/2025] [Indexed: 04/29/2025] Open
Abstract
BACKGROUND Pancreatic ductal adenocarcinoma (PDAC), a challenging and malignant cancer, primarily originates from the exocrine cells of the pancreas. The superfamily of solute carrier (SLC) transporters, consisting of more than 450 proteins divided into 65 families, is integral to various cellular processes and represents a promising target in precision oncology. As therapeutic targets, SLC transporters are explored through an integrative analysis. MATERIALS AND METHODS The expression profiles of SLCs were systematically analyzed using mRNA data from The Cancer Genome Atlas (TCGA) and protein data from the Human Protein Atlas (HPA). Survival analysis was examined to evaluate the prognostic significance of SLC transporters for overall survival (OS) and disease-specific survival (DSS). Genetic alterations were examined using cBioPortal, while structural studies were performed with AlphaFold and AlphaMissense to predict functional impacts. Furthermore, Gene Set Enrichment Analysis (GSEA) was carried out to identify oncogenic pathways linked to SLC transporter expression. RESULTS SLC transporters were significantly upregulated in tumors relative to normal tissues. Higher expression levels of SLC39A10 (HR = 1.89, p = 0.0026), SLC22B5 (HR = 1.84, p = 0.0042), SLC55A2 (HR = 2.15, p = 0.00023), and SLC30A6 (HR = 1.90, p = 0.003) were strongly associated with unfavorable OS, highlighting their connection to poor prognosis in PDAC. GSEA highlighted that these four transporters are significantly involved in key oncogenic pathways, such as epithelial-mesenchymal transition (EMT), TNF-α signaling, and angiogenesis. CONCLUSIONS The study identifies four SLCs as therapeutic targets in PDAC, highlighting their crucial role in essential metabolic pathways. These findings lay the groundwork for developing next-generation metabolic anti-cancer treatment to improve survival for PDAC patients.
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Affiliation(s)
- Sang Yeon Cho
- Graduate School of New Drug Discovery and Development, Chungnam National University, Daejeon 34134, Republic of Korea;
- CHOMEDICINE Inc., TIPS Town, Chungnam National University, Daejeon 34134, Republic of Korea
| | - Hyuk Soo Eun
- Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon 35015, Republic of Korea
- Department of Internal Medicine, Chungnam National University Hospital, Daejeon 35015, Republic of Korea
| | - Jaejeung Kim
- Department of Computer Science and Engineering, Chungnam National University, Daejeon 34134, Republic of Korea;
| | - Yun Dam Ko
- Seoul Teunteun Rehabilitation Clinic, Jeungpyeong-gun, Chungcheongbuk-do 27937, Republic of Korea
| | - Woo Sun Rou
- Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon 35015, Republic of Korea
- Department of Internal Medicine, Chungnam National University Sejong Hospital, Sejong 30099, Republic of Korea
| | - Jong Seok Joo
- Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon 35015, Republic of Korea
- Department of Internal Medicine, Chungnam National University Sejong Hospital, Sejong 30099, Republic of Korea
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Yu XL, Zhou LY, Huang X, Li XY, Wang MK, Yang JS. Role of nutrition in diabetes mellitus and infections. World J Clin Cases 2025; 13:94389. [PMID: 39866654 PMCID: PMC11577521 DOI: 10.12998/wjcc.v13.i3.94389] [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: 03/18/2024] [Revised: 09/28/2024] [Accepted: 10/21/2024] [Indexed: 11/12/2024] Open
Abstract
In this editorial, we have commented on the article that has been published in the recent issue of World Journal of Clinical Cases. The authors have described a case of unilateral thyroid cyst and have opined that the acute onset of infection may be linked to diabetes mellitus (DM). We have focused on the role of nutrition in the association between DM and infection. Patients with DM are at a high risk of infection, which could also be attributed to nutrition-related factors. Nutritional interventions for patients with diabetes are mainly based on a low-calorie diet, which can be achieved by adhering to a low-carbohydrate diet. However, dietary fiber supplementation is recommended to maintain the diversity of the gut microbiota. Furthermore, high-quality protein can prevent the increased risk of infection due to malnutrition. Supplementation of vitamins C, vitamins A, vitamins D, and folic acid improves blood sugar control and facilitates immune regulation. Mineral deficiencies augment the risk of infection, but the relationship with diabetes is mostly U-shaped and a good intake should be maintained.
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Affiliation(s)
- Xue-Lu Yu
- Naval Medical Center of PLA, Naval Medical University, Shanghai 200052, China
| | - Li-Yun Zhou
- Naval Medical Center of PLA, Naval Medical University, Shanghai 200052, China
| | - Xiao Huang
- Naval Medical Center of PLA, Naval Medical University, Shanghai 200052, China
| | - Xin-Yue Li
- Naval Medical Center of PLA, Naval Medical University, Shanghai 200052, China
| | - Ming-Ke Wang
- Naval Medical Center of PLA, Naval Medical University, Shanghai 200052, China
| | - Ji-Shun Yang
- Naval Medical Center of PLA, Naval Medical University, Shanghai 200052, China
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El-Saadony MT, Fang G, Yan S, Alkafaas SS, El Nasharty MA, Khedr SA, Hussien AM, Ghosh S, Dladla M, Elkafas SS, Ibrahim EH, Salem HM, Mosa WFA, Ahmed AE, Mohammed DM, Korma SA, El-Tarabily MK, Saad AM, El-Tarabily KA, AbuQamar SF. Green Synthesis of Zinc Oxide Nanoparticles: Preparation, Characterization, and Biomedical Applications - A Review. Int J Nanomedicine 2024; 19:12889-12937. [PMID: 39651353 PMCID: PMC11624689 DOI: 10.2147/ijn.s487188] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2024] [Accepted: 10/17/2024] [Indexed: 12/11/2024] Open
Abstract
Over the last decade, biomedical nanomaterials have garnered significant attention due to their remarkable biological properties and diverse applications in biomedicine. Metal oxide nanoparticles (NPs) are particularly notable for their wide range of medicinal uses, including antibacterial, anticancer, biosensing, cell imaging, and drug/gene delivery. Among these, zinc oxide (ZnO) NPs stand out for their versatility and effectiveness. Recently, ZnO NPs have become a primary material in various sectors, such as pharmaceutical, cosmetic, antimicrobials, construction, textile, and automotive industries. ZnO NPs can generate reactive oxygen species and induce cellular apoptosis, thus underpinning their potent anticancer and antibacterial properties. To meet the growing demand, numerous synthetic approaches have been developed to produce ZnO NPs. However, traditional manufacturing processes often involve significant economic and environmental costs, prompting a search for more sustainable alternatives. Intriguingly, biological synthesis methods utilizing plants, plant extracts, or microorganisms have emerged as ideal for producing ZnO NPs. These green production techniques offer numerous medicinal, economic, environmental, and health benefits. This review highlights the latest advancements in the green synthesis of ZnO NPs and their biomedical applications, showcasing their potential to revolutionize the field with eco-friendly and cost-effective solutions.
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Affiliation(s)
- Mohamed T El-Saadony
- Department of Agricultural Microbiology, Faculty of Agriculture, Zagazig University, Zagazig, 44511, Egypt
| | - Guihong Fang
- School of Public Health, Heinz Mehlhorn Academician Workstation, Hainan Medical University, Haikou, Hainan, 571199, People’s Republic of China
- Qionghai People’s Hospital, Qionghai, Hainan, 571400, People’s Republic of China
| | - Si Yan
- Qionghai People’s Hospital, Qionghai, Hainan, 571400, People’s Republic of China
| | - Samar Sami Alkafaas
- Molecular Cell Biology Unit, Division of Biochemistry, Department of Chemistry, Faculty of Science, Tanta University, Tanta, 31527, Egypt
| | - Mahmoud A El Nasharty
- Department of Chemistry, Faculty of Science, Ain Shams University, Cairo, 11566, Egypt
| | - Sohila A Khedr
- Industrial Biotechnology Department, Faculty of Science, Tanta University, Tanta, 31733, Egypt
| | - Aya Misbah Hussien
- Biotechnology Department at Institute of Graduate Studies and Research, Alexandria University, Alexandria, 21531, Egypt
| | - Soumya Ghosh
- Natural and Medical Sciences Research Center, University of Nizwa, Nizwa, 616, Oman
| | - Mthokozisi Dladla
- Human Molecular Biology Unit (School of Biomedical Sciences), Faculty of Health Sciences, University of the Free State, Bloemfontein, 9300, South Africa
| | - Sara Samy Elkafas
- Production Engineering and Mechanical Design Department, Faculty of Engineering, Menofia University, Shebin El Kom, Menofia, 32511, Egypt
- Faculty of Control System and Robotics, ITMO University, Saint-Petersburg, 197101, Russia
| | - Essam H Ibrahim
- Biology Department, Faculty of Science, King Khalid University, Abha, 61413, Saudi Arabia
- Blood Products Quality Control and Research Department, National Organization for Research and Control of Biologicals, Cairo, 12611, Egypt
| | - Heba Mohammed Salem
- Department of Poultry Diseases, Faculty of Veterinary Medicine, Cairo University, Giza, 12211, Egypt
| | - Walid F A Mosa
- Plant Production Department (Horticulture-Pomology), Faculty of Agriculture, Saba Basha, Alexandria University, Alexandria, 21531, Egypt
| | - Ahmed Ezzat Ahmed
- Biology Department, Faculty of Science, King Khalid University, Abha, 61413, Saudi Arabia
| | - Dina Mostafa Mohammed
- Nutrition and Food Sciences Department, National Research Centre, Dokki, Giza, 12622, Egypt
| | - Sameh A Korma
- Department of Food Science, Faculty of Agriculture, Zagazig University, Zagazig, 44511, Egypt
| | | | - Ahmed M Saad
- Department of Biochemistry, Faculty of Agriculture, Zagazig University, Zagazig, 44511, Egypt
| | - Khaled A El-Tarabily
- Department of Biology, College of Science, United Arab Emirates University, Al Ain, 15551, United Arab Emirates
| | - Synan F AbuQamar
- Department of Biology, College of Science, United Arab Emirates University, Al Ain, 15551, United Arab Emirates
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Sankova M, Nikolenko V, Oganesyan M, Vinnik Y, Gavryushova L, Redina S, Rizaeva N, Sankov A, Bulygin K, Vovkogon A, Pontes-Silva A, Zharikov Y. Zinc pathogenic importance in correcting immunity and restoring public health in the post-COVID period: An overview. Cytokine 2024; 184:156761. [PMID: 39307118 DOI: 10.1016/j.cyto.2024.156761] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2024] [Revised: 08/30/2024] [Accepted: 09/13/2024] [Indexed: 10/30/2024]
Abstract
CONTEXT The problem of correcting immune system function and compensating for co-morbidities becomes particularly clinically significant in the post-COVID period. There is evidence that certain trace elements in the human body, particularly zinc ions, play a critical role in restoring the function of the immune system and internal organs. OBJECTIVE To analyze the mechanisms of zinc action maintaining the body homeostasis in order to justify pathogenetically the inclusion of zinc drugs in the therapy of patients in the post-COVID period. METHODS Data from Elsevier, Global Health, PubMed-NCBI, Embase, MEDLINE, Scopus, Research gate, RSCI Scopus, Cochrane Library, Google Academy, e-LIBRARY.RU and CyberLeninka were used. RESULTS This review showed that the importance of zinc in maintaining body homeostasis in the post-COVID period is determined by its multifaceted effect on all parts of the immune system, its anti-inflammatory activity, antimicrobial properties and participation in the restoration of internal organ function. Elimination of zinc deficiency in the post-COVID period is essential to support immunity, compensate for comorbidities and reduce the risk of complications. The impossibility of synthesizing zinc in the body requires its constant intake in sufficient quantities. Zinc levels are significantly reduced after infectious diseases, as this element is specifically distributed to organs and tissues to maintain immunological and metabolic functions. The degree of zinc deficiency is associated with the severity of COVID-19 and the post-COVID period. It is pathogenetically justified to prescribe zinc drugs in the post-COVID period, the choice of which should take into account comorbidities and severity of hypozincemia. CONCLUSION Regularly administered therapy with zinc drugs in the post-COVID period will help correct the population immunity and restore public health.
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Affiliation(s)
- Maria Sankova
- I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia.
| | - Vladimir Nikolenko
- I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia.
| | - Marine Oganesyan
- I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia.
| | - Yurii Vinnik
- Voino-Yasenetsky Krasnoyarsk State Medical University, Krasnoyarsk, Russia.
| | - Liliya Gavryushova
- Saratov State Medical University named after V. I. Razumovsky, Saratov, Russia.
| | - Sofya Redina
- I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia.
| | - Negorya Rizaeva
- I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia.
| | - Aleksey Sankov
- I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia.
| | - Kirill Bulygin
- I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia.
| | - Andzhela Vovkogon
- I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia.
| | - André Pontes-Silva
- Postgraduate Program in Physical Therapy, Department of Physical Therapy, Universidade Federal de São Carlos, São Carlos, São Paulo, Brazil.
| | - Yury Zharikov
- I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia.
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Yang Y, Wang P, Guo J, Ma T, Hu Y, Huang L, Xing B, He Y, Xi J. Zinc Overload Induces Damage to H9c2 Cardiomyocyte Through Mitochondrial Dysfunction and ROS-Mediated Mitophagy. Cardiovasc Toxicol 2023; 23:388-405. [PMID: 37845565 DOI: 10.1007/s12012-023-09811-8] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2023] [Accepted: 09/23/2023] [Indexed: 10/18/2023]
Abstract
Zinc homeostasis is essential for maintaining redox balance, cell proliferation, and apoptosis. However, excessive zinc exposure is toxic and leads to mitochondrial dysfunction. In this study, we established a zinc overload model by treating rat cardiomyocyte H9c2 cells with Zn2+ at different concentrations. Our results showed that zinc overload increased LDH and reactive oxygen species (ROS) levels, leading to cell death, mitochondrial membrane potential decrease and impaired mitochondrial function and dynamics. Furthermore, zinc overload activated the PINK1/Parkin signaling pathway and induced mitochondrial autophagy via ROS, while NAC inhibited mitophagy and weakened the activation of PINK1/Parkin pathway, thereby preserving mitochondrial biogenesis. In addition, our data also showed that Mfn2 deletion increased ROS production and exacerbated cytotoxicity induced by zinc overload. Our results therefore suggest that Zn2+-induced ROS generation causes mitochondrial autophagy and mitochondrial dysfunction, damaging H9c2 cardiomyocytes. Additionally, Mfn2 may play a key role in zinc ion-mediated endoplasmic reticulum and mitochondrial interactions. Our results provide a new perspective on zinc-induced toxicology.
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Affiliation(s)
- Ying Yang
- Basic School of Medicine, Hebei Key Laboratory for Chronic Diseases, North China University of Science and Technology, Tangshan, China
| | - Pei Wang
- School of Public Health, North China University of Science and Technology, Tangshan, China
| | - Jiabao Guo
- Clinic School of Medicine and Affiliated Hospital, Hebei Key Laboratory of Medical-Industrial Integration Precision Medicine, North China University of Science and Technology, Tangshan, 063000, China
| | - Tingting Ma
- Clinic School of Medicine and Affiliated Hospital, Hebei Key Laboratory of Medical-Industrial Integration Precision Medicine, North China University of Science and Technology, Tangshan, 063000, China
| | - Youcheng Hu
- Basic School of Medicine, Hebei Key Laboratory for Chronic Diseases, North China University of Science and Technology, Tangshan, China
| | - Luyao Huang
- Basic School of Medicine, Hebei Key Laboratory for Chronic Diseases, North China University of Science and Technology, Tangshan, China
| | - Bohan Xing
- Basic School of Medicine, Hebei Key Laboratory for Chronic Diseases, North China University of Science and Technology, Tangshan, China
| | - Yonggui He
- Clinic School of Medicine and Affiliated Hospital, Hebei Key Laboratory of Medical-Industrial Integration Precision Medicine, North China University of Science and Technology, Tangshan, 063000, China.
- Affiliated Hospital, North China University of Science and Technology, Tangshan, China.
| | - Jinkun Xi
- Basic School of Medicine, Hebei Key Laboratory for Chronic Diseases, North China University of Science and Technology, Tangshan, China.
- Clinic School of Medicine and Affiliated Hospital, Hebei Key Laboratory of Medical-Industrial Integration Precision Medicine, North China University of Science and Technology, Tangshan, 063000, China.
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Chen A, Gao G, Lian G, Gong J, Luo L, Liu J, Chen W, Xu C, Wang H, Xie L. Zinc promotes cell proliferation via regulating metal-regulatory transcription factor 1 expression and transcriptional activity in pulmonary arterial hypertension. Cell Cycle 2023; 22:1284-1301. [PMID: 37128643 PMCID: PMC10193901 DOI: 10.1080/15384101.2023.2205209] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2022] [Revised: 12/30/2022] [Accepted: 04/17/2023] [Indexed: 05/03/2023] Open
Abstract
Metal responsive transcription factor 1 (MTF-1) is a zinc-dependent transcription factor involved in the development of pulmonary arterial hypertension (PAH), which is a life-threatening disease characterized by elevated pulmonary artery pressure and pulmonary vascular remodeling. However, little is known about the role and regulatory signaling of MTF-1 in PAH. This study aimed to investigate the effect and mechanism of MTF-1 on the proliferation of pulmonary arterial smooth muscle cells (PASMCs). Several techniques including intracellular-free zinc detected by fluorescent indicator-fluozinc-3-AM, western blot, luciferase reporter, and cell proliferation assay were conducted to perform a comprehensive analysis of MTF-1 in proliferation of PASMCs in PAH. Increased cytosolic zinc was shown in monocrotaline (MCT)-PASMCs and ZnSO₄-treated PASMCs, which led to overexpression and overactivation of MTF-1, followed by the up-regulation of placental growth factor (PlGF). Elevated MTF-1 and PlGF were observed in western blot, and high transcriptional activity of MTF-1 was confirmed by luciferase reporter in ZnSO4-treated cells. Further investigation of cell proliferation revealed a favorable impact of zinc ions on PASMCs proliferation, with the deletion of Mtf-1/Plgf attenuating ZnSO4-induced proliferation. Flow cytometry analysis showed that blockade of PKC signaling inhibited the cell cycle of MCT-PASMCs and ZnSO4-treated PASMCs. The Zinc/PKC/MTF-1/PlGF pathway is involved in the up-regulatory effect on the PASMCs proliferation in the process of PAH. This study provided novel insight into zinc homeostasis in the pathogenesis of PAHs, and the regulation of MTF-1 might be a potential target for therapeutic intervention in PAH.
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Affiliation(s)
- Ai Chen
- Department of Geriatrics, The First Affiliated Hospital of Fujian Medical University, Fuzhou, People’s Republic of China
- Fujian Hypertension Research Institute, The First Affiliated Hospital of Fujian Medical University, Fuzhou, People’s Republic of China
- Clinical Research Center for Geriatric Hypertension Disease of Fujian province, The First Affiliated Hospital of Fujian Medical University, Fuzhou, People’s Republic of China
- Branch of National Clinical Research Center for Aging and Medicine, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, People’s Republic of China
- Department of Geriatrics, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, People’s Republic of China
| | - Gufeng Gao
- Department of Geriatrics, The First Affiliated Hospital of Fujian Medical University, Fuzhou, People’s Republic of China
- Fujian Hypertension Research Institute, The First Affiliated Hospital of Fujian Medical University, Fuzhou, People’s Republic of China
- Clinical Research Center for Geriatric Hypertension Disease of Fujian province, The First Affiliated Hospital of Fujian Medical University, Fuzhou, People’s Republic of China
- Branch of National Clinical Research Center for Aging and Medicine, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, People’s Republic of China
- Department of Geriatrics, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, People’s Republic of China
| | - Guili Lian
- Department of Geriatrics, The First Affiliated Hospital of Fujian Medical University, Fuzhou, People’s Republic of China
- Fujian Hypertension Research Institute, The First Affiliated Hospital of Fujian Medical University, Fuzhou, People’s Republic of China
- Clinical Research Center for Geriatric Hypertension Disease of Fujian province, The First Affiliated Hospital of Fujian Medical University, Fuzhou, People’s Republic of China
- Branch of National Clinical Research Center for Aging and Medicine, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, People’s Republic of China
- Department of Geriatrics, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, People’s Republic of China
| | - Jin Gong
- Department of Geriatrics, The First Affiliated Hospital of Fujian Medical University, Fuzhou, People’s Republic of China
- Fujian Hypertension Research Institute, The First Affiliated Hospital of Fujian Medical University, Fuzhou, People’s Republic of China
- Clinical Research Center for Geriatric Hypertension Disease of Fujian province, The First Affiliated Hospital of Fujian Medical University, Fuzhou, People’s Republic of China
- Branch of National Clinical Research Center for Aging and Medicine, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, People’s Republic of China
- Department of Geriatrics, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, People’s Republic of China
| | - Li Luo
- Department of Geriatrics, The First Affiliated Hospital of Fujian Medical University, Fuzhou, People’s Republic of China
- Fujian Hypertension Research Institute, The First Affiliated Hospital of Fujian Medical University, Fuzhou, People’s Republic of China
- Clinical Research Center for Geriatric Hypertension Disease of Fujian province, The First Affiliated Hospital of Fujian Medical University, Fuzhou, People’s Republic of China
- Branch of National Clinical Research Center for Aging and Medicine, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, People’s Republic of China
- Department of Geriatrics, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, People’s Republic of China
| | - Junping Liu
- Department of Geriatrics, The First Affiliated Hospital of Fujian Medical University, Fuzhou, People’s Republic of China
- Fujian Hypertension Research Institute, The First Affiliated Hospital of Fujian Medical University, Fuzhou, People’s Republic of China
- Clinical Research Center for Geriatric Hypertension Disease of Fujian province, The First Affiliated Hospital of Fujian Medical University, Fuzhou, People’s Republic of China
- Branch of National Clinical Research Center for Aging and Medicine, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, People’s Republic of China
- Department of Geriatrics, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, People’s Republic of China
| | - Weixiao Chen
- Fujian Hypertension Research Institute, The First Affiliated Hospital of Fujian Medical University, Fuzhou, People’s Republic of China
| | - Changsheng Xu
- Fujian Hypertension Research Institute, The First Affiliated Hospital of Fujian Medical University, Fuzhou, People’s Republic of China
| | - Huajun Wang
- Fujian Hypertension Research Institute, The First Affiliated Hospital of Fujian Medical University, Fuzhou, People’s Republic of China
| | - Liangdi Xie
- Department of Geriatrics, The First Affiliated Hospital of Fujian Medical University, Fuzhou, People’s Republic of China
- Fujian Hypertension Research Institute, The First Affiliated Hospital of Fujian Medical University, Fuzhou, People’s Republic of China
- Clinical Research Center for Geriatric Hypertension Disease of Fujian province, The First Affiliated Hospital of Fujian Medical University, Fuzhou, People’s Republic of China
- Branch of National Clinical Research Center for Aging and Medicine, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, People’s Republic of China
- Department of Geriatrics, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, People’s Republic of China
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7
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Zhu L, An P, Zhao W, Xia Y, Qi J, Luo J, Luo Y. Low Zinc Alleviates the Progression of Thoracic Aortic Dissection by Inhibiting Inflammation. Nutrients 2023; 15:1640. [PMID: 37049478 PMCID: PMC10096567 DOI: 10.3390/nu15071640] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2023] [Revised: 03/24/2023] [Accepted: 03/24/2023] [Indexed: 03/30/2023] Open
Abstract
Vascular inflammation triggers the development of thoracic aortic dissection (TAD). Zinc deficiency could dampen tissue inflammation. However, the role of zinc as a nutritional intervention in the progression of TAD remains elusive. In this study, we employed a classical β-aminopropionitrile monofumarate (BAPN)-induced TAD model in mice treated with low zinc and observed that the TAD progression was greatly ameliorated under low zinc conditions. Our results showed that low zinc could significantly improve aortic dissection and rupture (BAPN + low zinc vs. BAPN, 36% vs. 100%) and reduce mortality (BAPN + low zinc vs. BAPN, 22% vs. 57%). Mechanically, low zinc attenuated the infiltration of macrophages and inhibited the expression of inflammatory cytokines, suppressed the phenotype switch of vascular smooth muscle cells from contractile to synthetic types, and eventually alleviated the development of TAD. In conclusion, this study suggested that low zinc may serve as a potential nutritional intervention approach for TAD prevention.
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Affiliation(s)
- Lin Zhu
- Department of Nutrition and Health, China Agricultural University, Beijing 100193, China
- Food Laboratory of Zhongyuan, Luohe 462300, China
| | - Peng An
- Department of Nutrition and Health, China Agricultural University, Beijing 100193, China
| | - Wenting Zhao
- Department of Nutrition and Health, China Agricultural University, Beijing 100193, China
| | - Yi Xia
- Department of Nutrition and Health, China Agricultural University, Beijing 100193, China
| | - Jingyi Qi
- Department of Nutrition and Health, China Agricultural University, Beijing 100193, China
- Food Laboratory of Zhongyuan, Luohe 462300, China
| | - Junjie Luo
- Department of Nutrition and Health, China Agricultural University, Beijing 100193, China
- Food Laboratory of Zhongyuan, Luohe 462300, China
| | - Yongting Luo
- Department of Nutrition and Health, China Agricultural University, Beijing 100193, China
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8
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Chen X, He C, Zhang K, Wang J, Ding X, Zeng Q, Peng H, Bai J, Lv L, Xuan Y, Bai S. Comparison of zinc bioavailability in zinc-glycine and zinc-methionine chelates for broilers fed with a corn-soybean meal diet. Front Physiol 2022; 13:983954. [PMID: 36467690 PMCID: PMC9714021 DOI: 10.3389/fphys.2022.983954] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2022] [Accepted: 11/02/2022] [Indexed: 11/26/2023] Open
Abstract
The objective of this study was to compare the bioavailability of zinc (Zn) from zinc-glycine (Zn-Gly) and zinc-methionine (Zn-Met) as compared with zinc sulfate (ZnSO4) used as a standard in broilers. A total of 1,200 one-day-old male broilers (Cobb 500) were randomly allotted to one of 10 treatments with eight replicate cages of 15 birds each. The broilers were fed a corn-soybean meal basal diet (containing 26.46 mg Zn/kg; control) or the basal diet added with 40, 80, and 120 mg Zn/kg as Zn-Gly, Zn-Met, or ZnSO4 for 14 days. The relative bioavailability value (RBV) was calculated based on multiple linear regression slope ratios of Zn concentrations in tibia and pancreas, pancreas metallothionein (MT) concentration, and pancreas MT mRNA abundance on added Zn intake. When comparing the control with all Zn-supplemented treatments, Zn addition did not significantly affect average feed intake and bodyweight gain during days 1-14 (p > 0.10). However, Zn concentrations in the tibia, pancreas, and liver and pancreas MT concentration and MT mRNA abundance increased in all Zn-supplemented treatments compared with the control (p < 0.05), and these indices increased linearly (p < 0.001) with increasing added Zn levels on days 7 and 14. The RBV of Zn as Zn-Met was similar to that as Zn-Gly or ZnSO4 (p > 0.40) on days 7 and 14, based on tibia and pancreas Zn. In contrast, on days 7 and 14, the RBVs of Zn were in the following order: Zn-Met > Zn-Gly > ZnSO4 (p < 0.05), based on pancreas MT concentration. The bioavailable Zn from Zn-Met was 1.20 or 1.25 times that from Zn-Gly on day 7 or 14, respectively, evaluated by pancreas MT content. The RBV of Zn as Zn-Met was similar to that as Zn-Gly or ZnSO4 on day 7, whereas it was higher than that as Zn-Gly or ZnSO4 on day 14, based on pancreas MT mRNA abundance. In conclusion, Zn-Met had higher bioavailable Zn than Zn-Gly for the starter broilers fed with the corn-soybean meal diet, using pancreas MT concentration as the response criterion.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | | | - Shiping Bai
- Animal Nutrition Institute, Feed Engineering Research Centre of Sichuan Province, Sichuan Agricultural University, Chengdu, China
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9
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Kang J, Yan Q, Zhou C, Zhou X, Tan Z. Replacing ZnSO 4 with Zn-glycine in the diet of goat promotes the pancreatic function of the offspring. ANIMAL NUTRITION (ZHONGGUO XU MU SHOU YI XUE HUI) 2022; 12:63-71. [PMID: 36514374 PMCID: PMC9731826 DOI: 10.1016/j.aninu.2022.08.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/17/2021] [Revised: 06/20/2022] [Accepted: 08/12/2022] [Indexed: 12/16/2022]
Abstract
Zinc supplementation in the diet of goats affects pancreas development in offspring. However, the impact of maternal inorganic and organic zinc supplementation in offspring is poorly defined. In this study, 14 late-pregnant goats were assigned at random to the zinc sulfate group (ZnSO4, n = 7) and the zinc-glycine chelate group (Zn-Gly, n = 7), respectively. Serum samples and pancreas tissue were collected from kids whose mothers were fed ZnSO4 and Zn-Gly at the late pregnancy, respectively. Histologic examination showed no morphologic differences between the 2 groups. Pancreatic zinc content in kids tended to be increased when replacing ZnSO4 with Zn-Gly. The serum insulin concentration was greater and glucagon less in the Zn-Gly group when compared to the ZnSO4 group. The activities of lipase and chymotrypsin were enhanced when replacing ZnSO4 with Zn-Gly. Proteomics results showed that 234 proteins were differentially expressed between the 2 groups, some of which were associated with the secretion of insulin, enzyme activity and signal transduction. The results suggested that supply of dietary Zn-Gly to goats during late pregnancy promoted pancreatic function in offspring compared with dietary ZnSO4 supplementation. This provides new information about pancreatic function when supplementing different zinc sources in the diets of late pregnant goats.
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Affiliation(s)
- Jinhe Kang
- CAS Key Laboratory for Agro-Ecological Processes in Subtropical Region, National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Hunan Provincial Key Laboratory of Animal Nutrition & Physiology and Metabolism, South-Central Experimental Station of Animal Nutrition and Feed Science in Ministry of Agriculture, Institute of Subtropical Agriculture, The Chinese Academy of Sciences, Changsha 410125, China
| | - Qiongxian Yan
- CAS Key Laboratory for Agro-Ecological Processes in Subtropical Region, National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Hunan Provincial Key Laboratory of Animal Nutrition & Physiology and Metabolism, South-Central Experimental Station of Animal Nutrition and Feed Science in Ministry of Agriculture, Institute of Subtropical Agriculture, The Chinese Academy of Sciences, Changsha 410125, China
| | - Chuanshe Zhou
- CAS Key Laboratory for Agro-Ecological Processes in Subtropical Region, National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Hunan Provincial Key Laboratory of Animal Nutrition & Physiology and Metabolism, South-Central Experimental Station of Animal Nutrition and Feed Science in Ministry of Agriculture, Institute of Subtropical Agriculture, The Chinese Academy of Sciences, Changsha 410125, China
| | - Xiaoling Zhou
- College of Animal Science, Tarim University, Alaer 843300, China
| | - Zhiliang Tan
- CAS Key Laboratory for Agro-Ecological Processes in Subtropical Region, National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Hunan Provincial Key Laboratory of Animal Nutrition & Physiology and Metabolism, South-Central Experimental Station of Animal Nutrition and Feed Science in Ministry of Agriculture, Institute of Subtropical Agriculture, The Chinese Academy of Sciences, Changsha 410125, China
- Corresponding author.
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10
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Luan F, Chen Y, Xu Y, Jiang X, Liu B, Wang Y. Associations between whole blood trace elements concentrations and HbA1c levels in patients with type 2 diabetes. Biometals 2022; 35:1011-1022. [PMID: 35864276 DOI: 10.1007/s10534-022-00419-z] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2022] [Accepted: 07/04/2022] [Indexed: 11/28/2022]
Abstract
Previous researches have been conducted to study the associations of trace elements on Type 2 diabetes (T2D) risk. The present study focuses on the evaluation of potential associations between trace elements and Hemoglobin A1c (HbA1c) in patients with T2D, via the determination of their levels in human whole blood. 100 diabetes without complications, 75 prediabetes and 40 apparently healthy subjects were studied. The levels of eleven trace elements including lithium (Li), vanadium (V), chromium (Cr), manganese (Mn), iron (Fe), cobalt (Co), copper (Cu), zinc (Zn), selenium (Se), strontium (Sr) and molybdenum (Mo) were measured using inductively coupled plasma mass spectrometry (ICP-MS). The levels of fasting glucose, HbA1c, Hemoglobin, lipid, liver function, kidney function, thyroid function and demographic data were obtained from the Laboratory Information System. Nonparametric correlation (Spearman) was used to analyze the relationship between trace elements and HbA1c. The contents of V, Cr, Mn, Fe, Co, Cu, Zn and Mo in diabetes increased comparing with the healthy subject while Li decreased. But the levels of Li, V, Cr, Mn, Co, Se and Mo negatively correlated with HbA1c in the diabetes subjects (r value: - 0.2189, - 0.2421, - 0.3260, - 0.2744, - 0.2812, - 0.2456, - 0.2240; 95% confidence interval - 0.4032 to - 0.0176, - 0.4235 to - 0.0420, - 0.4955 to - 0.1326, - 0.4515 to - 0.0765, - 0.4573 to - 0.0838, - 0.4266 to - 0.0458, - 0.4076 to - 0.0229; p < 0.05, p < 0.05, p < 0.001, p < 0.01, p < 0.01, p < 0.05, p < 0.05). Accordingly, the contents of V, Cr, Mn and Se showed lower in HbA1c ≥ 7.0% group in contrast to HbA1c < 7.0% group. No correlation of HbA1c (or FBG) and trace elements was found in the healthy subjects. Trace element levels and metabolic abnormalities of blood glucose may be mutually affected. The extra supplement of trace elements needs to be cautious.
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Affiliation(s)
- Fang Luan
- Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, No. 324 Jingwu Road, Jinan, Shandong, People's Republic of China
| | - Yuan Chen
- Department of Pediatry, Shandong Provincial Hospital Afliated to Shandong First Medical University, Jinan, Shandong, China
| | - Yanqiu Xu
- Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, No. 324 Jingwu Road, Jinan, Shandong, People's Republic of China
| | - Xuerui Jiang
- Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, No. 324 Jingwu Road, Jinan, Shandong, People's Republic of China
| | - Bin Liu
- Department of Biomedical Engineering, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
| | - Yong Wang
- Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, No. 324 Jingwu Road, Jinan, Shandong, People's Republic of China.
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11
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Beloucif A, Kechrid Z, Bekada AMA. Effect of Zinc Deficiency on Blood Glucose, Lipid Profile, and Antioxidant Status in Streptozotocin Diabetic Rats and the Potential Role of Sesame Oil. Biol Trace Elem Res 2022; 200:3236-3247. [PMID: 34613584 DOI: 10.1007/s12011-021-02934-5] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/12/2021] [Accepted: 09/20/2021] [Indexed: 02/08/2023]
Abstract
Zinc is recognized to have a crucial function in insulin production. As a result, its absence may have a deleterious impact on the progression of diabetes and associated consequences. So, this study was undertaken to evaluate the effect of sesame oil on biochemical parameters, zinc status, and oxidative stress biomarkers in streptozotocin (STZ)-induced diabetic rats fed zinc-deficient diet. Rats were divided into four groups. The first group consisted of non-diabetic rats that were fed in a sufficient zinc diet, whereas the second was a diabetic group which received also sufficient zinc diet, while the third and fourth groups were diabetic rats fed in a deficient zinc diet, one was non-treated and the other was treated with sesame oil 6% diet for 27 days. Zinc deficiency has affected the weight of the diabetic animals. It was also noticed that inadequate dietary zinc intake increased concentrations of glucose, cholesterol, triglycerides, malondialdehyde, and transaminases activities. Furthermore, zinc deficiency feed provoked a decrease in zinc level in tissues (femur, liver, and pancreas); glutathione concentration; and lactic dehydrogenase, amylase, catalase, superoxide dismutase, and glutathione-S-transferase activities. However, sesame oil treatment ameliorated all the previous parameters approximately to their normal values. It was found out that sesame oil supplementation is a potent factor in mitigating the oxidative severity of zinc deficiency in diabetes through its effective antioxidant potential.
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Affiliation(s)
- Afaf Beloucif
- Laboratory of Applied Biochemistry and Microbiology, Department of Biochemistry, Faculty of Sciences, University of Annaba, Annaba, Algeria
| | - Zine Kechrid
- Laboratory of Applied Biochemistry and Microbiology, Department of Biochemistry, Faculty of Sciences, University of Annaba, Annaba, Algeria.
| | - Ahmed Mohamed Ali Bekada
- Laboratory of Food Technology and Nutrition, Department of Biology, Faculty of Sciences, University of Mostaganem, Mostaganem, Algeria
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MacKenzie S, Bergdahl A. Zinc Homeostasis in Diabetes Mellitus and Vascular Complications. Biomedicines 2022; 10:biomedicines10010139. [PMID: 35052818 PMCID: PMC8773686 DOI: 10.3390/biomedicines10010139] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2021] [Revised: 01/03/2022] [Accepted: 01/04/2022] [Indexed: 12/20/2022] Open
Abstract
Oxidative stress represents an impaired metabolic system that promotes damage to cells and tissues. This is the predominant factor that leads to the development and progression of diabetes and diabetic complications. Research has indicated that zinc plays a consequential mechanistic role in the protection against oxidative stress as zinc is required for the proper functioning of the antioxidant system, the suppression of inflammatory mediators, and the modulation of zinc transporters. Recently, the mechanisms surrounding ZnT8, ZIP7, and metallothionein have shown to be of particular pathogenic importance and are considered as potential therapeutic targets in disease management. The literature has shown that zinc dysregulation is associated with diabetes and may be considered as a leading contributor to the deleterious vascular alterations exhibited by the disease. Although further investigation is required, studies have indicated the favorable use of zinc supplementation in the protection against and prevention of oxidative stress and its consequences over the course of the condition. This review aims to provide a comprehensive account of zinc homeostasis, the oxidative mechanisms governed by zinc status, current therapeutic targets, and the impact of zinc supplementation in the prevention of disease onset and in mitigating vascular complications.
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Distinct Hypoxia-Related Gene Profiling Characterizes Clinicopathological Features and Immune Status of Mismatch Repair-Deficient Colon Cancer. JOURNAL OF ONCOLOGY 2021; 2021:2427427. [PMID: 34917146 PMCID: PMC8670907 DOI: 10.1155/2021/2427427] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/18/2021] [Revised: 11/07/2021] [Accepted: 11/13/2021] [Indexed: 12/09/2022]
Abstract
Despite dramatic responses to immune checkpoint inhibitors (ICIs) in patients with colon cancer (CC) harboring deficient mismatch repair (dMMR), more than half of these patients ultimately progress and experience primary or secondary drug resistance. There is no useful biomarker that is currently validated to accurately predict this resistance or stratify patients who may benefit from ICI-based immunotherapy. As hypoxic and acidic tumor microenvironment would greatly impair tumor-suppressing functions of tumor-infiltrating lymphocytes (TILs), we sought to explore distinct immunological phenotypes by analysis of the intratumoral hypoxia state using a well-established gene signature. Based on the Gene Expression Omnibus (GEO) (n = 88) and The Cancer Genome Atlas (TCGA) (n = 49) databases of patients with CC, we found that dMMR CC patients could be separated into normoxia subgroup (NS) and hypoxia subgroup (HS) with different levels of expression of hypoxia-related genes (lower in NS group and higher in HS group) using NMF package. Tumoral parenchyma in the HS group had a relatively lower level of immune cell infiltration, particularly CD8+ T cells and M1 macrophages than the NS group, and coincided with higher expression of immune checkpoint molecules and C-X-C motif chemokines, which might be associated with ICI resistance and prognosis. Furthermore, three genes, namely, MT1E, MT2A, and MAFF, were identified to be differentially expressed between NS and HS groups in both GEO and TCGA cohorts. Based on these genes, a prognostic model with stable and valuable predicting ability has been built for clinical application. In conclusion, the varying tumor-immune microenvironment (TIME) classified by hypoxia-related genes might be closely associated with different therapeutic responses of ICIs and prognosis of dMMR CC patients.
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14
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Ściskalska M, Ołdakowska M, Milnerowicz H. Importance of Genetic Polymorphisms in MT1 and MT2 Genes in Metals Homeostasis and Their Relationship with the Risk of Acute Pancreatitis Occurrence in Smokers-Preliminary Findings. Int J Mol Sci 2021; 22:5725. [PMID: 34072023 PMCID: PMC8197913 DOI: 10.3390/ijms22115725] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2021] [Revised: 05/13/2021] [Accepted: 05/25/2021] [Indexed: 02/06/2023] Open
Abstract
This study was aimed at evaluating the changes in metallothionein (MT) concentration in the blood of patients with acute pancreatitis (AP) and healthy subjects, taking into account the extracellular (plasma) and intracellular (erythrocyte lysate) compartments. The impact of single-nucleotide polymorphisms (SNPs) in the MT1A (rs11640851), MT1B (rs964372) and MT2A (rs10636) genes on MT concentration and their association with the concentration of metals (Cu, Zn, Cd) and ceruloplasmin as Cu-related proteins were analyzed. The concentration of a high-sensitivity C-reactive protein (hs-CRP) and IL-6 as markers of inflammation, and malonyldialdehyde (MDA), superoxide dismutase (SODs) activity and the value of total antioxidant capacity (TAC) as parameters describing the pro/antioxidative balance were also assessed. In the AP patient groups, an increased MT concentration in erythrocyte lysate compared to healthy subjects was shown, especially in individuals with the GG genotype for rs964372 in the MT1B gene. A Zn concentration was especially decreased in the blood of smoking AP patients with the AA genotype for SNP rs11640851 in the MT1A gene and the GC genotype for SNP rs10636 in MT2A, compared to non-smokers with AP, which was accompanied by an increase in the value of the Cu/Zn ratio. The exposure to tobacco smoke xenobiotics increased the risk of AP occurrence in subjects with the CC genotype for SNP rs11640851 in the MT1A gene by more than fourfold. The investigated polymorphisms, rs11640851 in the MT1A gene, rs964372 in the MT1B gene and rs10636 in the MT2A gene, seem to be an important factor in maintaining homeostasis in an organism under oxidative stress conditions.
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Affiliation(s)
- Milena Ściskalska
- Department of Biomedical and Environmental Analyses, Faculty of Pharmacy, Wroclaw Medical University, 50-556 Wroclaw, Poland; (M.O.); (H.M.)
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15
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Zhu B, Huo R, Zhi Q, Zhan M, Chen X, Hua ZC. Increased expression of zinc transporter ZIP4, ZIP11, ZnT1, and ZnT6 predicts poor prognosis in pancreatic cancer. J Trace Elem Med Biol 2021; 65:126734. [PMID: 33631610 DOI: 10.1016/j.jtemb.2021.126734] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2020] [Revised: 02/11/2021] [Accepted: 02/15/2021] [Indexed: 01/19/2023]
Abstract
INTRODUCTION Zinc homeostasis is regulated by SLC39A/ZIP, SLC30A/ZnT, and metallothionein (MT) families in human cells. Zinc dyshomeostasis may affect or be affected by the abnormal behavior of cancer cells. Although decreased serum zinc levels are observed in patients with pancreatic adenocarcinoma (PAAD), limited information is available regarding the expression pattern and prognostic roles of zinc homeostasis-related genes in PAAD. OBJECTIVES The primary objective of this study was to explore the expression pattern and prognostic roles of zinc homeostasis-related genes in PAAD. METHODS The expression pattern of 35 known zinc homeostasis-related genes in PAAD was systemically explored based on RNA-sequencing data from the Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) projects. The association between the expression levels of zinc homeostasis-related genes and survival of PAAD patients was evaluated using the Kaplan-Meier method and the log-rank test. Expressional correlation between zinc homeostasis-related genes with potential prognostic value in PAAD and normal pancreatic controls was evaluated using Pearson's correlation analysis. Functional enrichment analyses were performed to elucidate possible mechanisms for the potential prognostic and therapeutic roles of these zinc homeostasis-related genes in PAAD. Effects of ZIP11, ZnT1, or ZnT6 knockdown on the proliferation and the migration of Capan-1 pancreatic cancer cells were assessed by the CCK-8 assay and the wound healing assay respectively. RESULTS We demonstrated that the expression levels of ZIP1, ZIP3, ZIP4, ZIP6, ZIP7, ZIP9, ZIP10, ZIP11, ZIP13, ZnT1, ZnT5, ZnT6, ZnT7, and ZnT9 were increased, whereas the expression levels of ZIP5, ZIP14, ZnT2, MT1 G, MT1H, and MT1X were decreased in PAAD tumors compared with normal pancreatic controls. Among these differentially-expressed genes related to zinc homeostasis, higher expression of ZIP4, ZIP11, ZnT1 or ZnT6 predicted poorer prognosis with the possible involvement of several cancer-related processes and pathways in PAAD patients. We further demonstrated that knockdown of ZIP11 attenuated Capan-1 cell proliferation with decreased activation of ERK1/2 pathway; knockdown of ZnT1 attenuated Capan-1 cell proliferation with decreased activation of ERK1/2, p38 MAPK, NF-kB, and mTOR pathways; knockdown of ZnT6 attenuated Capan-1 cell proliferation with decreased activation of ERK1/2, p38 MAPK, and NF-kB pathways. CONCLUSIONS Higher expression of the zinc transporter ZIP4, ZIP11, ZnT1 or ZnT6 predicted poorer prognosis in patients with PAAD. These findings provide new clues for understanding the complex relationship between zinc homeostasis and pancreatic cancer.
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Affiliation(s)
- Bo Zhu
- School of Biopharmacy, China Pharmaceutical University, Nanjing 211198, PR China; School of Medicine and Holistic Integrative Medicine and Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210023, PR China; School of Life Sciences, Nanjing University, Nanjing 210023, PR China.
| | - Ruwei Huo
- School of Medicine and Holistic Integrative Medicine and Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210023, PR China
| | - Qi Zhi
- School of Medicine and Holistic Integrative Medicine and Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210023, PR China
| | - Mingjie Zhan
- School of Biopharmacy, China Pharmaceutical University, Nanjing 211198, PR China
| | - Xiao Chen
- School of Medicine and Holistic Integrative Medicine and Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210023, PR China; School of Life Sciences, Nanjing University, Nanjing 210023, PR China
| | - Zi-Chun Hua
- School of Biopharmacy, China Pharmaceutical University, Nanjing 211198, PR China; School of Life Sciences, Nanjing University, Nanjing 210023, PR China; Changzhou High-Tech Research Institute of Nanjing University and Jiangsu Target Pharma Laboratories Inc., Changzhou 213164, PR China.
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16
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Ferguson MQ, DeRosa MC. Optimized experimental pre-treatment strategy for temporary inhibition of islet amyloid polypeptide aggregation. Biochem Biophys Rep 2021; 26:100964. [PMID: 33912690 PMCID: PMC8063701 DOI: 10.1016/j.bbrep.2021.100964] [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: 10/02/2020] [Revised: 02/21/2021] [Accepted: 02/22/2021] [Indexed: 11/24/2022] Open
Abstract
Islet amyloid polypeptide (IAPP) is a neuroendocrine hormone from pancreatic β-cells. Misfolded, aggregated IAPP is believed to be toxic to islet cells and amyloid deposits in the pancreas are pathological hallmarks of type 2 diabetes. Rapid fibrillization of this peptide makes it difficult to study in its soluble form, impeding a better understanding of its role. In this study, a variety of popular pretreatment methods were tested for their ability to delay aggregation of IAPP, including solutions of hexafluoroisopropanol, sodium hydroxide, hydrochloric acid, phosphate buffered saline, ammonium hydroxide, as well as tris buffer at different pH and containing either calcium (II), zinc (II), or iron (II). Aggregation was assessed using the thioflavin T fluorescence assay as well as by transmission electron microscopy. Tris buffer at pH 8.1 containing Zn(II) was found to have the best balance of temporary inhibition of aggregation and biological relevance.
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Affiliation(s)
- Madison Q Ferguson
- Department of Chemistry, Carleton University, 1125 Colonel By Drive, Ottawa, Ontario, K1S 5B6, Canada
| | - Maria C DeRosa
- Department of Chemistry, Carleton University, 1125 Colonel By Drive, Ottawa, Ontario, K1S 5B6, Canada
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17
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Barragán-Álvarez CP, Padilla-Camberos E, Díaz NF, Cota-Coronado A, Hernández-Jiménez C, Bravo-Reyna CC, Díaz-Martínez NE. Loss of Znt8 function in diabetes mellitus: risk or benefit? Mol Cell Biochem 2021; 476:2703-2718. [PMID: 33666829 DOI: 10.1007/s11010-021-04114-4] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2020] [Accepted: 02/18/2021] [Indexed: 12/13/2022]
Abstract
The zinc transporter 8 (ZnT8) plays an essential role in zinc homeostasis inside pancreatic β cells, its function is related to the stabilization of insulin hexameric form. Genome-wide association studies (GWAS) have established a positive and negative relationship of ZnT8 variants with type 2 diabetes mellitus (T2DM), exposing a dual and controversial role. The first hypotheses about its role in T2DM indicated a higher risk of developing T2DM for loss of function; nevertheless, recent GWAS of ZnT8 loss-of-function mutations in humans have shown protection against T2DM. With regard to the ZnT8 role in T2DM, most studies have focused on rodent models and common high-risk variants; however, considerable differences between human and rodent models have been found and the new approaches have included lower-frequency variants as a tool to clarify gene functions, allowing a better understanding of the disease and offering possible therapeutic targets. Therefore, this review will discuss the physiological effects of the ZnT8 variants associated with a major and lower risk of T2DM, emphasizing the low- and rare-frequency variants.
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Affiliation(s)
- Carla P Barragán-Álvarez
- Biotecnología Médica y Farmacéutica, Centro de Investigación y Asistencia en Tecnología y Diseño del Estado de Jalisco, Guadalajara, Mexico
| | - Eduardo Padilla-Camberos
- Biotecnología Médica y Farmacéutica, Centro de Investigación y Asistencia en Tecnología y Diseño del Estado de Jalisco, Guadalajara, Mexico
| | - Nestor F Díaz
- Departamento de Fisiología y Desarrollo Celular, Instituto Nacional de Perinatología, Mexico City, Mexico
| | - Agustín Cota-Coronado
- Biotecnología Médica y Farmacéutica, Centro de Investigación y Asistencia en Tecnología y Diseño del Estado de Jalisco, Guadalajara, Mexico
| | - Claudia Hernández-Jiménez
- Departamento de Cirugía Experimental, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, Mexico
| | - Carlos C Bravo-Reyna
- Departamento de Cirugía Experimental, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Nestor E Díaz-Martínez
- Biotecnología Médica y Farmacéutica, Centro de Investigación y Asistencia en Tecnología y Diseño del Estado de Jalisco, Guadalajara, Mexico.
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18
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Rios-Lugo MJ, Madrigal-Arellano C, Gaytán-Hernández D, Hernández-Mendoza H, Romero-Guzmán ET. Association of Serum Zinc Levels in Overweight and Obesity. Biol Trace Elem Res 2020; 198:51-57. [PMID: 32020525 DOI: 10.1007/s12011-020-02060-8] [Citation(s) in RCA: 53] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2019] [Accepted: 01/30/2020] [Indexed: 02/06/2023]
Abstract
Low levels of zinc (Zn) have adverse effects on physiological and metabolic functions in humans, especially in processes linked with obesity. In this work, serum Zn levels and their associations with biochemical parameters (glucose, triglycerides, and total cholesterol), sex, and body mass index (BMI) were determined. The distribution of the study sample by sex was homogeneous: 52.6% were women and 47.4% were men. Women had higher BMI and Zn levels (normal weight and obesity) than men, but the differences in BMI and serum Zn levels by sex were not significant (p > 0.05). Nevertheless, the results obtained showed a decrease in serum Zn levels in overweight and obese individuals (p < 0.05) and a negative correlation between BMI and serum Zn levels (r = - 0.663 and p < 0.001); additionally, a significant correlation was identified between cholesterol and triglyceride values (r = 0.493 and p < 0.001). In conclusion, this study demonstrated decreased serum Zn levels in overweight and obese individuals.
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Affiliation(s)
- María Judith Rios-Lugo
- Unidad de Posgrado, Facultad de Enfermería y Nutrición, UASLP, Avda. Niño Artillero 130, CP 78210, San Luis Potosí, S.L.P., Mexico
- Sección de Medicina Molecular y Traslacional, Centro de Investigación en Ciencias de Salud y Biomedicina. UASLP, Avda Sierra Leona 550, CP 78210, San Luis, S.L.P., Mexico
| | - Casandra Madrigal-Arellano
- Unidad de Posgrado, Facultad de Enfermería y Nutrición, UASLP, Avda. Niño Artillero 130, CP 78210, San Luis Potosí, S.L.P., Mexico
| | - Darío Gaytán-Hernández
- Unidad de Posgrado, Facultad de Enfermería y Nutrición, UASLP, Avda. Niño Artillero 130, CP 78210, San Luis Potosí, S.L.P., Mexico
| | - Héctor Hernández-Mendoza
- Instituto de Investigación de Zonas Desérticas, UASLP, Altair 200, CP 78377, San Luis, S.L.P., Mexico.
- Universidad del Centro de México, Capitán Caldera 75, CP 78250, San Luis, S.L.P., Mexico.
| | - Elizabeth Teresita Romero-Guzmán
- Laboratorio Nacional de Investigaciones en Forense Nuclear (LANAFONU), Gerencia de Tecnología Nuclear, Dirección de Investigación Tecnológica, Carretera México s/n, CP 52750, Toluca, La Marquesa Ocoyoacác, Mexico
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Magrì A, Tabbì G, Di Natale G, La Mendola D, Pietropaolo A, Zoroddu MA, Peana M, Rizzarelli E. Zinc Interactions with a Soluble Mutated Rat Amylin to Mimic Whole Human Amylin: An Experimental and Simulation Approach to Understand Stoichiometry, Speciation and Coordination of the Metal Complexes. Chemistry 2020; 26:13072-13084. [DOI: 10.1002/chem.202002114] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2020] [Revised: 05/29/2020] [Indexed: 01/27/2023]
Affiliation(s)
- Antonio Magrì
- Consiglio Nazionale delle Ricerche Istituto di Cristallografia Via P. Gaifami 18 95126 Catania Italy
| | - Giovanni Tabbì
- Consiglio Nazionale delle Ricerche Istituto di Cristallografia Via P. Gaifami 18 95126 Catania Italy
| | - Giuseppe Di Natale
- Consiglio Nazionale delle Ricerche Istituto di Cristallografia Via P. Gaifami 18 95126 Catania Italy
| | - Diego La Mendola
- Dipartimento di Farmacia Università di Pisa Via Bonanno Pisano, 6 56126 Pisa Italy
- Consorzio Interuniversitario di Ricerca in Chimica dei, Metalli nei Sistemi Biologici (CIRCMSB) Via Celso Ulpiani 27 70126 Bari Italy
| | - Adriana Pietropaolo
- Dipartimento di Scienze della Salute Università “Magna Graecia” di Catanzaro Campus Universitario, Viale Europa 88100 Catanzaro Italy
| | | | - Massimiliano Peana
- Dipartimento di Chimica e Farmacia University of Sassari Via Vienna 2 07100 Sassari Italy
| | - Enrico Rizzarelli
- Consiglio Nazionale delle Ricerche Istituto di Cristallografia Via P. Gaifami 18 95126 Catania Italy
- Consorzio Interuniversitario di Ricerca in Chimica dei, Metalli nei Sistemi Biologici (CIRCMSB) Via Celso Ulpiani 27 70126 Bari Italy
- Dipartimento di Scienze Chimiche Università degli Studi di Catania Viale A. Doria 6 95125 Catania Italy
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Guo J, Xie J, Zhou B, Găman MA, Kord-Varkaneh H, Clark CC, Salehi-Sahlabadi A, Li Y, Han X, Hao Y, Liang Y. The influence of zinc supplementation on IGF-1 levels in humans: A systematic review and meta-analysis. JOURNAL OF KING SAUD UNIVERSITY - SCIENCE 2020; 32:1824-1830. [DOI: 10.1016/j.jksus.2020.01.018] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/29/2024]
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Advances of Zinc Signaling Studies in Prostate Cancer. Int J Mol Sci 2020; 21:ijms21020667. [PMID: 31963946 PMCID: PMC7014440 DOI: 10.3390/ijms21020667] [Citation(s) in RCA: 43] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2019] [Revised: 01/16/2020] [Accepted: 01/17/2020] [Indexed: 12/16/2022] Open
Abstract
Prostate cancer (PCa) is one of the most common cancers and the second leading cause of cancer-related death among men worldwide. Despite progresses in early diagnosis and therapeutic strategies, prognosis for patients with advanced PCa remains poor. Noteworthily, a unique feature of healthy prostate is its highest level of zinc content among all soft tissues in the human body, which dramatically decreases during prostate tumorigenesis. To date, several reviews have suggested antitumor activities of zinc and its potential as a therapeutic strategy of PCa. However, an overview about the role of zinc and its signaling in PCa is needed. Here, we review literature related to the content, biological function, compounds and clinical application of zinc in PCa. We first summarize zinc content in prostate tissue and sera of PCa patients with their clinical relevance. We then elaborate biological functions of zinc signaling in PCa on three main aspects, including cell proliferation, death and tumor metastasis. Finally, we discuss clinical applications of zinc-containing compounds and proteins involved in PCa signaling pathways. Based on currently available studies, we conclude that zinc plays a tumor suppressive role and can serve as a biomarker in PCa diagnosis and therapies.
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Whitehouse MW. Conditional nutrition (I): concerning zinc as a beneficial but variable regulator of inflammation and experimental arthritis. Inflammopharmacology 2019; 28:1401-1406. [PMID: 31832849 DOI: 10.1007/s10787-019-00669-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2019] [Accepted: 11/14/2019] [Indexed: 11/25/2022]
Abstract
This article extends the concept of conditional pharmacology (Whitehouse and Vernon-Roberts 1991; Whitehouse 1995) that considers how both internal factors/disease and external/environmental factors may alter the availability or efficacy of exogenous drugs. The same and other conditioning factors may also affect the utility and value of many nutriceuticals that may be clearly beneficial in the context of inflammation but sometimes showing quite variable pharmaco-activity. This is illustrated by considering some factors affecting the bioavailability and pharmaco-efficacy of dietary ionic zinc, Zn (II) an essential trace metal and a critical regulator of inflammation and tissue repair. With chronic zinc deficiency (zincopenia) due to diet, drugs and/or disease, we can usually survive-but may not necessarily thrive. Some strategies to minimise zincopenia are considered, based upon finding efficient means for (1) preventing its cause and/or (2) using parenteral delivery of zinc supplements to circumvent dietary and enteric impediments to zinc bio-availability.
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Affiliation(s)
- Michael W Whitehouse
- School of Medicine, Griffith University, Gold Coast, QLD, 4222, Australia. .,, PO Box 6168, Woolloongabba, QLD, 4102, Australia.
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