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Du Y, Huo Y, Yang Y, Lin P, Liu W, Wang Z, Zeng W, Li J, Liang Z, Yuan C, Zhu J, Luo Z, Liu Y, Ma C, Yang C. Role of sirtuins in obesity and osteoporosis: molecular mechanisms and therapeutic targets. Cell Commun Signal 2025; 23:20. [PMID: 39799353 PMCID: PMC11724515 DOI: 10.1186/s12964-024-02025-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2024] [Accepted: 12/30/2024] [Indexed: 01/15/2025] Open
Abstract
The prevalence of obesity and osteoporosis (OP) represents a significant public health concern on a global scale. A substantial body of evidence indicates that there is a complex relationship between obesity and OP, with a correlation between the occurrence of OP and obesity. In recent years, sirtuins have emerged as a prominent area of interest in the fields of aging and endocrine metabolism. Among the various research avenues exploring the potential of sirtuins, the effects of these proteins on obesity and OP have garnered significant attention from numerous researchers. Sirtuins regulate energy balance and lipid balance, which in turn inhibit the process of adipogenesis. Additionally, sirtuins regulate the balance between osteogenic and osteoblastic activity, which protects against the development of OP. However, no study has yet provided a comprehensive discussion of the relationship between the three: sirtuins, obesity, and OP. This paper will therefore describe the relationship between sirtuins and obesity, the relationship between sirtuins and OP, and a discussion focusing on the possibility of treating OP caused by obesity by targeting sirtuins. This will be based on the common influences on the occurrence of obesity and OP (such as mesenchymal stem cells, gut microbiota, and insulin). Finally, the potential of SIRT1, an important member of sirtuins, in polyphenolic natural products for the treatment of obesity and OP will be presented. This will contribute to a better understanding of the interactions between sirtuins and obesity and bone, which will facilitate the development of new therapeutic strategies for obesity and OP in the future.
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Grants
- Nos. 2021B1515140012, 2023A1515010083 the Natural Science Foundation of Guangdong Province
- No. 20211800905342 the Dongguan Science and Technology of Social Development Program
- No. A2024398 the Medical Scientific Research Foundation of Guangdong Province
- No. k202005 the Research and Development Fund of Dongguan People' s Hospital
- Nos. GDMU2021003, GDMU2021049, GDMU2022031, GDMU2022047, GDMU2022063, GDMU2022077, GDMU2022078, GDMU2023008, GDMU2023015, GDMU2023026, GDMU2023042, GDMU2023102 the Guangdong Medical University Students' Innovation and Entrepreneurship Training Program
- Nos. 202210571008, S202210571075, 202310571031, S202310571047, S202310571078, S202310571063, S202310571077 the Provincial and National College Students' Innovation and Entrepreneurship Training Program
- No. 4SG24028G the Guangdong Medical University-Southern Medical University twinning research team project
- No. PF100-2-01 "Climbing 100" Joint Merit Training Program Funded Project
- Nos. 2023ZYDS001, 2023FZDS001, 2023FYDB010 the Guangdong Medical University Students' Innovation Experiment Program
- the Research and Development Fund of Dongguan People’ s Hospital
- the Guangdong Medical University Students’ Innovation and Entrepreneurship Training Program
- the Provincial and National College Students’ Innovation and Entrepreneurship Training Program
- the Cai Limin National Traditional Chinese Medicine Inheritance Studio
- the Guangdong Medical University Students’ Innovation Experiment Program
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Affiliation(s)
- Yikuan Du
- Central Laboratory, The Tenth Affiliated Hospital of Southern Medical University, Dongguan, 523059, China
| | - Yuying Huo
- Dongguan Key Laboratory of Stem Cell and Regenerative Tissue Engineering, The First Dongguan Affiliated Hospital, School of Basic Medical Sciences, Guangdong Medical University, Dongguan, 523808, China
| | - Yujia Yang
- Dongguan Key Laboratory of Stem Cell and Regenerative Tissue Engineering, The First Dongguan Affiliated Hospital, School of Basic Medical Sciences, Guangdong Medical University, Dongguan, 523808, China
| | - Peiqi Lin
- Dongguan Key Laboratory of Stem Cell and Regenerative Tissue Engineering, The First Dongguan Affiliated Hospital, School of Basic Medical Sciences, Guangdong Medical University, Dongguan, 523808, China
| | - Wuzheng Liu
- Dongguan Key Laboratory of Stem Cell and Regenerative Tissue Engineering, The First Dongguan Affiliated Hospital, School of Basic Medical Sciences, Guangdong Medical University, Dongguan, 523808, China
| | - Ziqin Wang
- Dongguan Key Laboratory of Stem Cell and Regenerative Tissue Engineering, The First Dongguan Affiliated Hospital, School of Basic Medical Sciences, Guangdong Medical University, Dongguan, 523808, China
| | - Wenqi Zeng
- Dongguan Key Laboratory of Stem Cell and Regenerative Tissue Engineering, The First Dongguan Affiliated Hospital, School of Basic Medical Sciences, Guangdong Medical University, Dongguan, 523808, China
| | - Jiahui Li
- Dongguan Key Laboratory of Stem Cell and Regenerative Tissue Engineering, The First Dongguan Affiliated Hospital, School of Basic Medical Sciences, Guangdong Medical University, Dongguan, 523808, China
| | - Zhonghan Liang
- Dongguan Key Laboratory of Stem Cell and Regenerative Tissue Engineering, The First Dongguan Affiliated Hospital, School of Basic Medical Sciences, Guangdong Medical University, Dongguan, 523808, China
| | - Chenyue Yuan
- Dongguan Key Laboratory of Stem Cell and Regenerative Tissue Engineering, The First Dongguan Affiliated Hospital, School of Basic Medical Sciences, Guangdong Medical University, Dongguan, 523808, China
| | - Jinfeng Zhu
- Dongguan Key Laboratory of Stem Cell and Regenerative Tissue Engineering, The First Dongguan Affiliated Hospital, School of Basic Medical Sciences, Guangdong Medical University, Dongguan, 523808, China
| | - Ziyi Luo
- Dongguan Key Laboratory of Stem Cell and Regenerative Tissue Engineering, The First Dongguan Affiliated Hospital, School of Basic Medical Sciences, Guangdong Medical University, Dongguan, 523808, China
| | - Yi Liu
- The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan, 523808, China
| | - Chunling Ma
- The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan, 523808, China
| | - Chun Yang
- Dongguan Key Laboratory of Stem Cell and Regenerative Tissue Engineering, The First Dongguan Affiliated Hospital, School of Basic Medical Sciences, Guangdong Medical University, Dongguan, 523808, China.
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Ghassemifard L, Hasanlu M, Parsamanesh N, Atkin SL, Almahmeed W, Sahebkar A. Cell Therapies and Gene Therapy for Diabetes: Current Progress. Curr Diabetes Rev 2025; 21:e130524229899. [PMID: 38747221 DOI: 10.2174/0115733998292392240425122326] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2023] [Revised: 03/07/2024] [Accepted: 03/21/2024] [Indexed: 04/23/2025]
Abstract
The epidemic of diabetes continues to be an increasing problem, and there is a need for new therapeutic strategies. There are several promising drugs and molecules in synthetic medicinal chemistry that are developing for diabetes. In addition to this approach, extensive studies with gene and cell therapies are being conducted. Gene therapy is an existing approach in treating several diseases, such as cancer, autoimmune diseases, heart disease and diabetes. Several reports have also suggested that stem cells have the differentiation capability to functional pancreatic beta cell development in vitro and in vivo, with the utility to treat diabetes and prevent the progression of diabetes-related complications. In this current review, we have focused on the different types of cell therapies and vector-based gene therapy in treating or preventing diabetes.
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Affiliation(s)
- Leila Ghassemifard
- Department of Physiology, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
- Department of Persian Medicine, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Masumeh Hasanlu
- Department of Internal Medicine, Vali-e-Asr Hospital, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Negin Parsamanesh
- Metabolic Diseases Research Center, Zanjan University of Medical Sciences, Zanjan, Iran
- Department of Genetics and Molecular Medicine, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Stephen L Atkin
- Research Department, Royal College of Surgeons in Ireland Bahrain, Adliya, Bahrain
| | - Wael Almahmeed
- Heart and Vascular Institute, Cleveland Clinic Abu Dhabi, Abu Dhabi, United Arab Emirates
| | - Amirhossein Sahebkar
- Center for Global Health Research, Saveetha Medical College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, India
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
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Lin Z, Lin J, Huang A, Zhang Z, Wu X, Yin G, Wei C, Xu W. Angiotensin (1-7) Improves Pancreatic Islet Function via Upregulating PDX-1 and GCK: A Dose-Dependent Study in Mice. Int J Endocrinol 2024; 2024:1672096. [PMID: 39734383 PMCID: PMC11671625 DOI: 10.1155/ije/1672096] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2023] [Revised: 10/16/2024] [Accepted: 10/24/2024] [Indexed: 12/31/2024] Open
Abstract
Purpose: This study aimed to verify the effect of angiotensin (1-7) on improving islet function and further explore the signaling pathway that may be involved in this improvement. It also aimed to explore the effects of angiotensin (1-7) on blood glucose levels, islet function, and morphological changes in db/db mice and its potential signal pathway. Methods: Forty-five db/db mice were divided randomly into a model control group and different doses of angiotensin (1-7) intervention groups (0, 150, 300, and 600 μg/kg/d), while seven db/m mice were assigned as the normal control group. The angiotensin (1-7) intervention groups received daily intraperitoneal administration for 8 weeks, whereas the normal control group was injected intraperitoneally with an equal volume of normal saline every day for 8 weeks. Changes in weight and food intake of mice were detected. Effect of angiotensin (1-7) on lipid metabolism, islet function, the morphology of pancreatic islets, and β-cell mass on mice were evaluated. The expression of PDX-1 and GCK in pancreatic tissue was verified. Results: The group receiving angiotensin (1-7) at a dosage of 600 μg/kg/d showed a significant decrease in body weight, triglyceride levels, and fasting blood glucose, along with an improvement in glucose tolerance. In the 300 μg/kg/d group, angiotensin (1-7) tended to increase the total volume of islets. Moreover, the intervention groups exhibited a significant increase in the ratio of β cells, small islets (30-80 μm in diameter), as well as the expression levels of PDX-1 and GCK in pancreatic tissue. Conclusion: Angiotensin (1-7) could improve glucose and lipid metabolism and islet function by promoting the expression of PDX-1 and GCK genes in the pancreas of db/db mice.
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Affiliation(s)
- Ziwei Lin
- Shantou University Medical College, Shantou, China
- Department of Endocrinology and Metabolism, The First Affiliated Hospital of Shantou University Medical College, Shantou, China
| | - Jiaqi Lin
- Shantou University Medical College, Shantou, China
- Department of Endocrinology and Metabolism, The First Affiliated Hospital of Shantou University Medical College, Shantou, China
| | - Anqi Huang
- Shantou University Medical College, Shantou, China
- Department of Endocrinology and Metabolism, The First Affiliated Hospital of Shantou University Medical College, Shantou, China
| | - Zixu Zhang
- Shantou University Medical College, Shantou, China
- Department of Endocrinology and Metabolism, The First Affiliated Hospital of Shantou University Medical College, Shantou, China
| | - Xinyi Wu
- Shantou University Medical College, Shantou, China
- Department of Endocrinology and Metabolism, The First Affiliated Hospital of Shantou University Medical College, Shantou, China
| | - Guoshu Yin
- Department of Endocrinology and Metabolism, The First Affiliated Hospital of Shantou University Medical College, Shantou, China
| | - Chiju Wei
- Multidisciplinary Research Center, Shantou University, Shantou, China
| | - Wencan Xu
- Department of Endocrinology and Metabolism, The First Affiliated Hospital of Shantou University Medical College, Shantou, China
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He XQ, Zou HD, Liu Y, Chen XJ, Atanasov AG, Wang XL, Xia Y, Ng SB, Matin M, Wu DT, Liu HY, Gan RY. Discovery of Curcuminoids as Pancreatic Lipase Inhibitors from Medicine-and-Food Homology Plants. Nutrients 2024; 16:2566. [PMID: 39125445 PMCID: PMC11314295 DOI: 10.3390/nu16152566] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2024] [Revised: 07/20/2024] [Accepted: 07/26/2024] [Indexed: 08/12/2024] Open
Abstract
Researchers are increasingly interested in discovering new pancreatic lipase inhibitors as anti-obesity ingredients. Medicine-and-food homology plants contain a diverse set of natural bioactive compounds with promising development potential. This study screened and identified potent pancreatic lipase inhibitors from 20 commonly consumed medicine-and-food homology plants using affinity ultrafiltration combined with spectroscopy and docking simulations. The results showed that turmeric exhibited the highest pancreatic lipase-inhibitory activity, and curcumin, demethoxycurcumin, and bisdemethoxycurcumin were discovered to be potent pancreatic lipase inhibitors within the turmeric extract, with IC50 values of 0.52 ± 0.04, 1.12 ± 0.05, and 3.30 ± 0.08 mg/mL, respectively. In addition, the enzymatic kinetics analyses demonstrated that the inhibition type of the three curcuminoids was the reversible competitive model, and curcumin exhibited a higher binding affinity and greater impact on the secondary structure of pancreatic lipase than found with demethoxycurcumin or bisdemethoxycurcumin, as observed through fluorescence spectroscopy and circular dichroism. Furthermore, docking simulations supported the above experimental findings, and revealed that the three curcuminoids might interact with amino acid residues in the binding pocket of pancreatic lipase through non-covalent actions, such as hydrogen bonding and π-π stacking, thereby inhibiting the pancreatic lipase. Collectively, these findings suggest that the bioactive compounds of turmeric, in particular curcumin, can be promising dietary pancreatic lipase inhibitors for the prevention and management of obesity.
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Affiliation(s)
- Xiao-Qin He
- Institute of Urban Agriculture, Chinese Academy of Agricultural Sciences, Chengdu National Agricultural Science & Technology Center, Chengdu 610213, China; (X.-Q.H.); (H.-D.Z.); (Y.L.); (Y.X.)
- West China School of Public Health, West China Fourth Hospital, Sichuan University, Chengdu 610041, China
| | - Hai-Dan Zou
- Institute of Urban Agriculture, Chinese Academy of Agricultural Sciences, Chengdu National Agricultural Science & Technology Center, Chengdu 610213, China; (X.-Q.H.); (H.-D.Z.); (Y.L.); (Y.X.)
| | - Yi Liu
- Institute of Urban Agriculture, Chinese Academy of Agricultural Sciences, Chengdu National Agricultural Science & Technology Center, Chengdu 610213, China; (X.-Q.H.); (H.-D.Z.); (Y.L.); (Y.X.)
| | - Xue-Jiao Chen
- College of Food and Bioengineering, Xihua University, Chengdu 610039, China; (X.-J.C.); (X.-L.W.)
| | - Atanas G. Atanasov
- Ludwig Boltzmann Institute Digital Health and Patient Safety, Medical University of Vienna, Spitalgasse 23, 1090 Vienna, Austria;
- Institute of Genetics and Animal Biotechnology, The Polish Academy of Sciences, Jastrzebiec, 05-552 Magdalenka, Poland;
| | - Xiao-Li Wang
- College of Food and Bioengineering, Xihua University, Chengdu 610039, China; (X.-J.C.); (X.-L.W.)
| | - Yu Xia
- Institute of Urban Agriculture, Chinese Academy of Agricultural Sciences, Chengdu National Agricultural Science & Technology Center, Chengdu 610213, China; (X.-Q.H.); (H.-D.Z.); (Y.L.); (Y.X.)
| | - Siew Bee Ng
- Singapore Institute of Food and Biotechnology Innovation (SIFBI), Agency for Science, Technology and Research (A*STAR), 31 Biopolis Way, Singapore 138669, Singapore;
| | - Maima Matin
- Institute of Genetics and Animal Biotechnology, The Polish Academy of Sciences, Jastrzebiec, 05-552 Magdalenka, Poland;
| | - Ding-Tao Wu
- Key Laboratory of Coarse Cereal Processing (Ministry of Agriculture and Rural Affairs), Sichuan Engineering & Technology Research Center of Coarse Cereal Industralization, School of Food and Biological Engineering, Chengdu University, Chengdu 610106, China;
| | - Hong-Yan Liu
- Institute of Urban Agriculture, Chinese Academy of Agricultural Sciences, Chengdu National Agricultural Science & Technology Center, Chengdu 610213, China; (X.-Q.H.); (H.-D.Z.); (Y.L.); (Y.X.)
| | - Ren-You Gan
- Singapore Institute of Food and Biotechnology Innovation (SIFBI), Agency for Science, Technology and Research (A*STAR), 31 Biopolis Way, Singapore 138669, Singapore;
- Department of Food Science and Nutrition, Faculty of Science, The Hong Kong Polytechnic University, Kowloon, Hong Kong SAR, China
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Abdalla MMI. Insulin resistance as the molecular link between diabetes and Alzheimer's disease. World J Diabetes 2024; 15:1430-1447. [PMID: 39099819 PMCID: PMC11292327 DOI: 10.4239/wjd.v15.i7.1430] [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: 02/14/2024] [Revised: 04/08/2024] [Accepted: 05/06/2024] [Indexed: 07/08/2024] Open
Abstract
Diabetes mellitus (DM) and Alzheimer's disease (AD) are two major health concerns that have seen a rising prevalence worldwide. Recent studies have indicated a possible link between DM and an increased risk of developing AD. Insulin, while primarily known for its role in regulating blood sugar, also plays a vital role in protecting brain functions. Insulin resistance (IR), especially prevalent in type 2 diabetes, is believed to play a significant role in AD's development. When insulin signalling becomes dysfunctional, it can negatively affect various brain functions, making individuals more susceptible to AD's defining features, such as the buildup of beta-amyloid plaques and tau protein tangles. Emerging research suggests that addressing insulin-related issues might help reduce or even reverse the brain changes linked to AD. This review aims to explore the rela-tionship between DM and AD, with a focus on the role of IR. It also explores the molecular mechanisms by which IR might lead to brain changes and assesses current treatments that target IR. Understanding IR's role in the connection between DM and AD offers new possibilities for treatments and highlights the importance of continued research in this interdisciplinary field.
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Affiliation(s)
- Mona Mohamed Ibrahim Abdalla
- Department of Human Biology, School of Medicine, International Medical University, Bukit Jalil 57000, Kuala Lumpur, Malaysia
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Abd El-Hack ME, Kamal M, Alazragi RS, Alreemi RM, Qadhi A, Ghafouri K, Azhar W, Shakoori AM, Alsaffar N, Naffadi HM, Taha AE, Abdelnour SA. Impacts of chitosan and its nanoformulations on the metabolic syndromes: a review. BRAZ J BIOL 2024; 83:e276530. [PMID: 38422267 DOI: 10.1590/1519-6984.276530] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2023] [Accepted: 11/15/2023] [Indexed: 03/02/2024] Open
Abstract
A significant public health issue worldwide is metabolic syndrome, a cluster of metabolic illnesses that comprises insulin resistance, obesity, dyslipidemia, hyperglycemia, and hypertension. The creation of natural treatments and preventions for metabolic syndrome is crucial. Chitosan, along with its nanoformulations, is an oligomer of chitin, the second-most prevalent polymer in nature, which is created via deacetylation. Due to its plentiful biological actions in recent years, chitosan and its nanoformulations have drawn much interest. Recently, the chitosan nanoparticle-based delivery of CRISPR-Cas9 has been applied in treating metabolic syndromes. The benefits of chitosan and its nanoformulations on insulin resistance, obesity, diabetes mellitus, dyslipidemia, hyperglycemia, and hypertension will be outlined in the present review, highlighting potential mechanisms for the avoidance and medication of the metabolic syndromes by chitosan and its nanoformulations.
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Affiliation(s)
- M E Abd El-Hack
- Zagazig University, Faculty of Agriculture, Department of Poultry, Zagazig, Egypt
| | - M Kamal
- Agricultural Research Center, Animal Production Research Institute, Dokki, Giza, Egypt
| | - R S Alazragi
- University of Jeddah, College of Science, Department of Biochemistry, Jeddah, Saudi Arabia
| | - R M Alreemi
- University of Jeddah, College of Science, Department of Biochemistry, Jeddah, Saudi Arabia
| | - A Qadhi
- Umm Al-Qura University, Faculty of Applied Medical Sciences, Clinical Nutrition Department, Makkah, Saudi Arabia
| | - K Ghafouri
- Umm Al-Qura University, Faculty of Applied Medical Sciences, Clinical Nutrition Department, Makkah, Saudi Arabia
| | - W Azhar
- Umm Al-Qura University, Faculty of Applied Medical Sciences, Clinical Nutrition Department, Makkah, Saudi Arabia
| | - A M Shakoori
- Umm Al-Qura University, Faculty of Applied Medical Sciences, Laboratory Medicine Department, Makkah, Kingdom of Saudi Arabia
| | - N Alsaffar
- Mohammed Al-Mana College for Medical Sciences, Biochemistry and Molecular Biology Department, Dammam, Saudi Arabia
| | - H M Naffadi
- Umm Al-Qura University, College of Medicine, Department of Medical Genetics, Makkah, Kingdom of Saudi Arabia
| | - A E Taha
- Alexandria University, Faculty of Veterinary Medicine, Department of Animal Husbandry and Animal Wealth Development, Edfina, Egypt
| | - S A Abdelnour
- Zagazig University, Faculty of Agriculture, Department of Animal Production, Zagazig, Egypt
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Du H, Li D, Molive LM, Wu N. Advances in free fatty acid profiles in gestational diabetes mellitus. J Transl Med 2024; 22:180. [PMID: 38374136 PMCID: PMC10875910 DOI: 10.1186/s12967-024-04922-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2023] [Accepted: 01/21/2024] [Indexed: 02/21/2024] Open
Abstract
The morbidity of gestational diabetes mellitus (GDM) is increasing and is associated with adverse perinatal outcomes and long-term maternal and infant health. The exact mechanism underlying changes in plasma free fatty acid (FFA) profiles in patients with GDM is unknown. However, it is believed that changes in diet and lipid metabolism may play a role. Fatty acids contain many specific FFAs, and the type of FFA has different impacts on physiological processes; hence, determining changes in FFAs in individual plasma is essential. Alterations in FFA concentration or profile may facilitate insulin resistance. Additionally, some FFAs show potential to predict GDM in early pregnancy and are strongly associated with the growth and development of the fetus and occurrence of macrosomia. Here, we aimed to review changes in FFAs in women with GDM and discuss the relationship of FFAs with GDM incidence and adverse outcomes.
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Affiliation(s)
- Haoyi Du
- Department of Endocrinology, Shengjing Hospital of China Medical University, Shenyang, 110004, People's Republic of China
| | - Danyang Li
- Department of Endocrinology, Shengjing Hospital of China Medical University, Shenyang, 110004, People's Republic of China
| | - Laura Monjowa Molive
- Department of Endocrinology, Shengjing Hospital of China Medical University, Shenyang, 110004, People's Republic of China
| | - Na Wu
- Department of Endocrinology, Shengjing Hospital of China Medical University, Shenyang, 110004, People's Republic of China.
- Medical Department, Shengjing Hospital of China Medical University, Liaoning Province, Shenyang, People's Republic of China.
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Zhang S, Zhang B, Liu Y, Li L. Adipokines in atopic dermatitis: the link between obesity and atopic dermatitis. Lipids Health Dis 2024; 23:26. [PMID: 38263019 PMCID: PMC10804547 DOI: 10.1186/s12944-024-02009-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2023] [Accepted: 01/08/2024] [Indexed: 01/25/2024] Open
Abstract
Atopic dermatitis (AD) is a chronic skin condition with intense pruritus, eczema, and dry skin. The recurrent intense pruritus and numerous complications in patients with AD can profoundly affect their quality of life. Obesity is one of its comorbidities that has been confirmed to be the hazard factor of AD and also worsen its severity. Nevertheless, the specific mechanisms that explain the connection between obesity and AD remain incompletely recognized. Recent studies have built hopes on various adipokines to explain this connection. Adipokines, which are disturbed by an obese state, may lead to immune system imbalances in people with AD and promote the development of the disease. This review focuses on the abnormal expression patterns of adipokines in patients with AD and their potential regulatory molecular mechanisms associated with AD. The connection between AD and obesity is elucidated through the involvement of adipokines. This conduces to the in-depth exploration of AD pathogenesis and provides a new perspective to develop therapeutic targets.
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Affiliation(s)
- Shiyun Zhang
- Eight-year Medical Doctor Program, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
- Department of Dermatology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases, Beijing, China, No. 1 Shuaifuyuan, 100730
| | - Bingjie Zhang
- Department of Dermatology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases, Beijing, China, No. 1 Shuaifuyuan, 100730
| | - Yuehua Liu
- Department of Dermatology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases, Beijing, China, No. 1 Shuaifuyuan, 100730
| | - Li Li
- Department of Dermatology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases, Beijing, China, No. 1 Shuaifuyuan, 100730.
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Wang X, Wang Y, Hou J, Liu H, Zeng R, Li X, Han M, Li Q, Ji L, Pan D, Jia W, Zhong W, Xu T. Plasma proteome profiling reveals the therapeutic effects of the PPAR pan-agonist chiglitazar on insulin sensitivity, lipid metabolism, and inflammation in type 2 diabetes. Sci Rep 2024; 14:638. [PMID: 38182717 PMCID: PMC10770401 DOI: 10.1038/s41598-024-51210-8] [Citation(s) in RCA: 7] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2023] [Accepted: 01/02/2024] [Indexed: 01/07/2024] Open
Abstract
Chiglitazar is a novel peroxisome proliferator-activated receptor (PPAR) pan-agonist, which passed phase III clinical trials and was newly approved in China for use as an adjunct to diet and exercise in glycemic control in adult patients with Type 2 Diabetes (T2D). To explore the circulating protein signatures associated with the administration of chiglitazar in T2D patients, we conducted a comparative longitudinal study using plasma proteome profiling. Of the 157 T2D patients included in the study, we administered chiglitazar to a specific group, while the controls were given either placebo or sitagliptin. The plasma proteomes were profiled at baseline and 12 and 24 weeks post-treatment using data-independent acquisition mass spectrometry (DIA-MS). Our study indicated that 13 proteins were associated with chiglitazar treatment in T2D patients, including 10 up-regulated proteins (SHBG, TF, APOA2, APOD, GSN, MBL2, CFD, PGLYRP2, A2M, and APOA1) and 3 down-regulated proteins (PRG4, FETUB, and C2) after treatment, which were implicated in the regulation of insulin sensitivity, lipid metabolism, and inflammation response. Our study provides insight into the response of chiglitazar treatment from a proteome perspective and demonstrates the multi-faceted effects of chiglitazar in T2D patients, which will help the clinical application of chiglitazar and further study of its action mechanism.
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Affiliation(s)
- Xingyue Wang
- National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China
- Sino-Danish College, University of Chinese Academy of Sciences, Beijing, China
| | - You Wang
- National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China
| | - Junjie Hou
- National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China
| | - Hongyang Liu
- National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China
| | - Rong Zeng
- CAS Key Laboratory of Systems Biology, CAS Center for Excellence in Molecular Cell Sciences, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, China
| | - Xiangyu Li
- Guangzhou National Laboratory, Guangzhou, China
| | - Mei Han
- Guangzhou National Laboratory, Guangzhou, China
| | - Qingrun Li
- CAS Key Laboratory of Systems Biology, CAS Center for Excellence in Molecular Cell Sciences, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, China
| | - Linong Ji
- Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China
| | - Desi Pan
- Shenzhen Chipscreen Biosciences Co., Ltd, Shenzhen, China
| | - Weiping Jia
- Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China
| | - Wen Zhong
- Guangzhou National Laboratory, Guangzhou, China.
| | - Tao Xu
- National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
- Guangzhou National Laboratory, Guangzhou, China.
- Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China.
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10
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Upadhyay M, Hosur RV, Jha A, Bharti K, Mali PS, Jha AK, Mishra B, Kumar A. Myricetin encapsulated chitosan nanoformulation for management of type 2 diabetes: Preparation, optimization, characterization and in vivo activity. BIOMATERIALS ADVANCES 2023; 153:213542. [PMID: 37418933 DOI: 10.1016/j.bioadv.2023.213542] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/11/2023] [Revised: 06/27/2023] [Accepted: 06/29/2023] [Indexed: 07/09/2023]
Abstract
Type 2 diabetes mellitus (T2DM) is a serious and alarming disease attracting widespread attention. It is not a single metabolic disease; over time, it leads to serious disorders, namely, diabetic nephropathy, neuropathy, retinopathy and several cardiovascular, hepatocellular complications. The increase in T2DM cases in recent times has attracted significant attention. Currently, the medications available have side effects, and injectables are painful, causing trauma to the patients. Therefore, it is imperative to come up with oral delivery. In this background we report here a nanoformulation carrying natural small molecule Myricetin (MYR) encapsulated within Chitosan nanoparticles (CHT-NPs). MYR-CHT-NPs were prepared by ionic gelation method and evaluated using different characterization techniques. The in vitro release of MYR from CHT NPs in different physiological media showed pH dependence. in vivo pharmacodynamic study followed by oral administration in Albino Wistar rats showed better glycaemic control than existing drug. Further, the optimized nanoparticles also exhibited controlled increase in weight as compared to Metformin. The biochemistry profile of rats treated with nanoformulation reduced the levels of several pathological biomarkers, indicating additional benefits of MYR. Histopathological images exhibited no toxicity or changes in the major organs section in contrast to normal control, suggesting safe oral administration of the encapsulated MYR. Thus, we conclude that MYR-CHT-NPs represent an attractive delivery vehicle in improving the blood glucose level with controlled weight and have the potential to be safely administered orally for the management of T2DM.
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Affiliation(s)
- Mansi Upadhyay
- Department of Biosciences & Bioengineering, Indian Institute of Technology Bombay, Mumbai 400076, India.
| | - Ramakrishna V Hosur
- Department of Biosciences & Bioengineering, Indian Institute of Technology Bombay, Mumbai 400076, India
| | - Abhishek Jha
- Department of Pharmaceutical Engineering & Technology, Indian Institute of Technology (BHU) Varanasi, 221005, India
| | - Kanchan Bharti
- Department of Pharmaceutical Engineering & Technology, Indian Institute of Technology (BHU) Varanasi, 221005, India
| | - Pramod S Mali
- Department of Biosciences & Bioengineering, Indian Institute of Technology Bombay, Mumbai 400076, India
| | - Akash Kumar Jha
- Department of Biosciences & Bioengineering, Indian Institute of Technology Bombay, Mumbai 400076, India
| | - Brahmeshwar Mishra
- Department of Pharmaceutical Engineering & Technology, Indian Institute of Technology (BHU) Varanasi, 221005, India
| | - Ashutosh Kumar
- Department of Biosciences & Bioengineering, Indian Institute of Technology Bombay, Mumbai 400076, India.
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11
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Zhao Q, Cheng N, Sun X, Yan L, Li W. The application of nanomedicine in clinical settings. Front Bioeng Biotechnol 2023; 11:1219054. [PMID: 37441195 PMCID: PMC10335748 DOI: 10.3389/fbioe.2023.1219054] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2023] [Accepted: 06/05/2023] [Indexed: 07/15/2023] Open
Abstract
As nanotechnology develops in the fields of mechanical engineering, electrical engineering, information and communication, and medical care, it has shown great promises. In recent years, medical nanorobots have made significant progress in terms of the selection of materials, fabrication methods, driving force sources, and clinical applications, such as nanomedicine. It involves bypassing biological tissues and delivering drugs directly to lesions and target cells using nanorobots, thus increasing concentration. It has also proved useful for monitoring disease progression, complementary diagnosis, and minimally invasive surgery. Also, we examine the development of nanomedicine and its applications in medicine, focusing on the use of nanomedicine in the treatment of various major diseases, including how they are generalized and how they are modified. The purpose of this review is to provide a summary and discussion of current research for the future development in nanomedicine.
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Affiliation(s)
- Qingsong Zhao
- Postdoctoral Programme of Meteria Medica Institute of Harbin University of Commerce, Harbin, China
| | - Nuo Cheng
- Department of Endocrinology, The Fourth Hospital of Harbin Medical University, Harbin, China
| | - Xuyan Sun
- Department of Endocrinology, The Fourth Hospital of Harbin Medical University, Harbin, China
| | - Lijun Yan
- Postdoctoral Programme of Meteria Medica Institute of Harbin University of Commerce, Harbin, China
| | - Wenlan Li
- Postdoctoral Programme of Meteria Medica Institute of Harbin University of Commerce, Harbin, China
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12
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Yuan Y, Zhang B, He J, Wei T, Liu D, Yang W, Guo C, Nie X. Combinations of Tibetan tea and medicine food homology herbs: A new strategy for obesity prevention. Food Sci Nutr 2023; 11:504-515. [PMID: 36655078 PMCID: PMC9834885 DOI: 10.1002/fsn3.3081] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2022] [Revised: 07/19/2022] [Accepted: 09/16/2022] [Indexed: 01/21/2023] Open
Abstract
Obesity has become a significant global public health problem. Functional drinks have been an essential direction for obesity prevention research. The present study investigated the preventive effect and safety of winter melon and lotus leaf Tibetan tea (WLTT, a compound tea drink based on Ya'an Tibetan Tea and medicine food homology herbs) on obesity. The rats' hypercaloric high-fat diet (HFD) obesity model was established to evaluate obesity prevention and explored the mechanism through intestinal flora regulation. The results showed that in obese rats with the intervention of WLTT (400, 800, and 1600 mg/kg BW), the body weight, fat accumulation, adipocyte cell size, serum lipid levels, and antioxidant enzyme activity (SOD, GSH-Px, and MDA) were progressively improved. 16S rRNA high-throughput sequencing showed that WLTT could improve intestinal flora disorders due to HFD, which significantly reversed the relative abundance of Firmicutes and the F/B ratio associated with an HFD, and significantly upregulated the relative abundance of Verrucomicrobia. At the genus level, the downregulation of the relative abundance of Akkermansia and unclassified_Lachnospiraceae groups, and the upregulation of the relative abundance of Romboutsia, Ruminococcus, Corynebacteriume, and Saccharibacteria_genera_incertae_sedis groups brought about by the HFD were significantly reversed. The results of the above experiments were compared favorably with those of a parallel experiment with Bi -Sheng -Yuan slimming tea (BSY, a functional drink based on green tea and medicine food homology herbs). Overall, the findings have provided that WLTT can prevent obesity owing to an HFD by regulating intestinal flora and has a good safety profile, and combinations of Tibetan tea and medicine food homology herbs could be a new option for obesity prevention.
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Affiliation(s)
- Ye Yuan
- Department of Pharmacy & Medical LaboratoryYa'an Polytechnic CollegeYa'anChina
- College of PharmacyZunyi Medical UniversityZunyiChina
| | - Bin Zhang
- Department of Pharmacy & Medical LaboratoryYa'an Polytechnic CollegeYa'anChina
| | - Jing‐liu He
- Department of Pharmacy & Medical LaboratoryYa'an Polytechnic CollegeYa'anChina
| | - Ting Wei
- Department of Pharmacy & Medical LaboratoryYa'an Polytechnic CollegeYa'anChina
| | - De‐jun Liu
- Department of Pharmacy & Medical LaboratoryYa'an Polytechnic CollegeYa'anChina
| | - Wen‐jun Yang
- Department of Pharmacy & Medical LaboratoryYa'an Polytechnic CollegeYa'anChina
| | - Cheng‐Yi Guo
- Department of Pharmacy & Medical LaboratoryYa'an Polytechnic CollegeYa'anChina
| | - Xu‐qiang Nie
- College of PharmacyZunyi Medical UniversityZunyiChina
- Key Laboratory of the Basic Pharmacology of the Ministry of EducationZunyi Medical UniversityZunyiChina
- Joint International Research Laboratory of Ethnomedicine of Chinese Ministry of EducationZunyi Medical UniversityZunyiChina
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13
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Abdollahi M, Kato M, Lanting L, Tunduguru R, Wang M, Wang Y, Fueger PT, Wang Q, Huang W, Natarajan R. miR-379 mediates insulin resistance and obesity through impaired angiogenesis and adipogenesis regulated by ER stress. MOLECULAR THERAPY. NUCLEIC ACIDS 2022; 30:115-130. [PMID: 36250205 PMCID: PMC9535382 DOI: 10.1016/j.omtn.2022.09.015] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/28/2022] [Accepted: 09/15/2022] [Indexed: 01/29/2023]
Abstract
We investigated the role of microRNA (miR-379) in the pathogenesis of obesity, adipose tissue dysfunction, and insulin resistance (IR). We used miR-379 knockout (miR-379KO) mice to test whether loss of miR-379 affects high-fat diet (HFD)-induced obesity and IR via dysregulation of key miR-379 targets in adipose tissue. Increases in body weight, hyperinsulinemia, and IR in wild-type (WT)-HFD mice were significantly attenuated in miR-379KO-HFD mice with some sex differences. Relative to control chow-fed mice, in WT-HFD mice, expression of miR-379 and C/EBP homologous protein (Chop) (pro-endoplasmic reticulum [ER] stress) and inflammation in perigonadal white adipose tissue (gWAT) were increased, whereas adipogenic genes and miR-379 target genes (Vegfb and Edem3) were decreased. These changes, as well as key parameters of brown adipose tissue dysfunction (including mitochondrial defects), were significantly attenuated in miR-379KO-HFD mice. WAT from obese human subjects with and without type 2 diabetes showed increased miR-379 and decreased miR-379 target genes. In cultured 3T3L1 pre-adipocytes, miR-379 inhibitors increased miR-379 targets and adipogenic genes. These data suggest that miR-379 plays an important role in HFD-induced obesity through increased adipose inflammation, mitochondrial dysfunction, and ER stress as well as impaired adipogenesis and angiogenesis. miR-379 inhibitors may be developed as novel therapies for obesity and associated complications.
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Affiliation(s)
- Maryam Abdollahi
- Department of Diabetes Complications and Metabolism, Arthur Riggs Diabetes and Metabolism Research Institute, Beckman Research Institute of City of Hope, Duarte, CA 91010, USA
| | - Mitsuo Kato
- Department of Diabetes Complications and Metabolism, Arthur Riggs Diabetes and Metabolism Research Institute, Beckman Research Institute of City of Hope, Duarte, CA 91010, USA
| | - Linda Lanting
- Department of Diabetes Complications and Metabolism, Arthur Riggs Diabetes and Metabolism Research Institute, Beckman Research Institute of City of Hope, Duarte, CA 91010, USA
| | - Ragadeepthi Tunduguru
- Department of Diabetes Complications and Metabolism, Arthur Riggs Diabetes and Metabolism Research Institute, Beckman Research Institute of City of Hope, Duarte, CA 91010, USA
| | - Mei Wang
- Department of Diabetes Complications and Metabolism, Arthur Riggs Diabetes and Metabolism Research Institute, Beckman Research Institute of City of Hope, Duarte, CA 91010, USA
| | - Yangmeng Wang
- Department of Diabetes Complications and Metabolism, Arthur Riggs Diabetes and Metabolism Research Institute, Beckman Research Institute of City of Hope, Duarte, CA 91010, USA
| | - Patrick T. Fueger
- Department of Molecular and Cellular Endocrinology, Arthur Riggs Diabetes and Metabolism Research Institute, Beckman Research Institute of City of Hope, Duarte, CA 91010, USA
- Comprehensive Metabolic Phenotyping Core, Beckman Research Institute of City of Hope, Duarte, CA 91010, USA
| | - Qiong Wang
- Department of Molecular and Cellular Endocrinology, Arthur Riggs Diabetes and Metabolism Research Institute, Beckman Research Institute of City of Hope, Duarte, CA 91010, USA
| | - Wendong Huang
- Department of Diabetes Complications and Metabolism, Arthur Riggs Diabetes and Metabolism Research Institute, Beckman Research Institute of City of Hope, Duarte, CA 91010, USA
| | - Rama Natarajan
- Department of Diabetes Complications and Metabolism, Arthur Riggs Diabetes and Metabolism Research Institute, Beckman Research Institute of City of Hope, Duarte, CA 91010, USA
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14
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Design of Smart Nanodiamonds: Introducing pH Sensitivity to Improve Nucleic Acid Carrier Efficiency of Diamoplexes. Pharmaceutics 2022; 14:pharmaceutics14091794. [PMID: 36145542 PMCID: PMC9501119 DOI: 10.3390/pharmaceutics14091794] [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: 07/29/2022] [Revised: 08/19/2022] [Accepted: 08/23/2022] [Indexed: 11/18/2022] Open
Abstract
The mechanism of cellular uptake and intracellular fate of nanodiamond/nucleic acid complexes (diamoplexes) are major determinants of its performance as a gene carrier. Our group designed lysine-nanodiamonds (K-NDs) as vectors for nucleic acid delivery. In this work, we modified the surface of K-NDs with histidine to overcome endo-lysosomal entrapment diamoplexes, the major rate limiting step in gene transfer. Histidine is conjugated onto the NDs in two configurations: lysyl-histidine-NDs (HK-NDs) where histidine is loaded on 100% of the lysine moieties and lysine/lysyl-histidine-NDs (H50K50-NDs) where histidine is loaded on 50% of the lysine moieties. Both HK-NDs and H50K50-NDs maintained the optimum size distribution (i.e., <200 nm) and a cationic surface (zeta potential > 20 mV), similar to K-NDs. HK-NDs binds plasmid deoxyribonucleic acid (pDNA) and small interfering ribonucleic acid (siRNA) forming diamoplexes at mass ratios of 10:1 and 60:1, respectively. H50K50-NDs significantly improved nucleic acid binding, forming diamoplexes at a 2:1 mass ratio with pDNA and a 30:1 mass ratio with siRNA, which are at values similar to the K-NDs. The amount of histidine on the surface also impacted the interactions with mammalian cells. The HK-NDs reduced the cell viability by 30% at therapeutic concentrations, while H50K50-NDs maintained more than 90% cell viability, even at the highest concentrations. H50K50-NDs also showed highest cellular uptake within 24 h, followed by K-NDs and HK-NDs. Most functionalized NDs show cellular exit after 5 days, leaving less than 10% of cells with internalized diamonds. The addition of histidine to the ND resulted in higher transfection of anti-green fluorescent protein siRNA (anti-GFP siRNA) with the fraction of GFP knockdown being 0.8 vs. 0.6 for K-NDs at a mass ratio of 50:1. H50K50-NDs further improved transfection by achieving a similar fraction of GFP knockdown (0.8) at a lower mass ratio of 30:1. Overall, this study provides evidence that the addition of histidine, a pH-modulating entity in the functionalization design at an optimized ratio, renders high efficiency to the diamoplexes. Further studies will elucidate the uptake mechanism and intracellular fate to build the relationship between physicochemical characteristics and biological efficacy and create a platform for solid-core nanoparticle-based gene delivery.
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15
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Dehghan M, Ghorbani F, Najafi S, Ravaei N, Karimian M, Kalhor K, Movafagh A, Mohsen Aghaei Zarch S. Progress toward molecular therapy for diabetes mellitus: A focus on targeting inflammatory factors. Diabetes Res Clin Pract 2022; 189:109945. [PMID: 35690269 DOI: 10.1016/j.diabres.2022.109945] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2022] [Revised: 04/22/2022] [Accepted: 06/06/2022] [Indexed: 11/03/2022]
Abstract
Diabetes mellitus (DM) has been the most prevalent global metabolic disease, turning into a serious risk for human health. Several researches have recorded a role for inflammation and immunity in the pathogenesis of both in T1DM and in T2DM. Lots of chemical agents are available to control and to cure diabetic patients, which are not always sufficient for euglycemia maintenance and late stage diabetic complications avoidance. Therefore, newborn therapeutic methods to refine clinical outcomes in DM are required. Nucleic-acid-based therapy also known as gene expression level regulator within the target cells has been calculated to be promising in various diseases. Thus, pronounced attempts have been dedicated to develop new targeted molecular therapy aimed at improving insulin resistance in DM. This review mainly focuses on recent progress in DM molecular therapy and whether, has potential efficacy against inflammatory mediators involved in DM.
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Affiliation(s)
- Mohadesse Dehghan
- Department of Microbiology, Faculity of Life Science, Islamic Azad University, North Tehran Branch, Tehran, Iran
| | - Fateme Ghorbani
- Department of Biology, Islamic Azad University, Tonekabon Branch, Mazandran, Iran
| | - Sajad Najafi
- Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Neda Ravaei
- Department of Genetics, Faculty of Basic Sciences, Islamic Azad University, Tehran, Iran
| | - Maede Karimian
- Protein Engineering Laboratory, Department of Medical Genetics, School of Medicine, Shahid Sadoughi University of Medical Science, Yazd, Iran
| | - Kambiz Kalhor
- Department of Earth and Planetary Sciences, University of Tennessee, Knoxville, USA
| | - Abolfazl Movafagh
- Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Seyed Mohsen Aghaei Zarch
- Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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16
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Aierken A, Li B, Liu P, Cheng X, Kou Z, Tan N, Zhang M, Yu S, Shen Q, Du X, Enkhbaatar BB, Zhang J, Zhang R, Wu X, Wang R, He X, Li N, Peng S, Jia W, Wang C, Hua J. Melatonin treatment improves human umbilical cord mesenchymal stem cell therapy in a mouse model of type II diabetes mellitus via the PI3K/AKT signaling pathway. Stem Cell Res Ther 2022; 13:164. [PMID: 35414044 PMCID: PMC9006413 DOI: 10.1186/s13287-022-02832-0] [Citation(s) in RCA: 36] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2021] [Accepted: 03/01/2022] [Indexed: 01/14/2023] Open
Abstract
BACKGROUND Mesenchymal stem cells (MSCs) are promising candidates for tissue regeneration and disease treatment. However, long-term in vitro passaging leads to stemness loss of MSCs, resulting in failure of MSC therapy. This study investigated whether the combination of melatonin and human umbilical cord mesenchymal stem cells (hUC-MSCs) was superior to hUC-MSCs alone in ameliorating high-fat diet and streptozocin (STZ)-induced type II diabetes mellitus (T2DM) in a mouse model. METHODS Mice were divided into four groups: normal control (NC) group; T2DM group; hUC-MSCs treatment alone (UCMSC) group and pretreatment of hUC-MSCs with melatonin (UCMSC/Mel) group. RESULTS RNA sequence analysis showed that certain pathways, including the signaling pathway involved in the regulation of cell proliferation signaling pathway, were regulated by melatonin. The blood glucose levels of the mice in the UCMSC and UCMSC/Mel treatment groups were significantly reduced compared with the T2DM group without treatment (P < 0.05). Furthermore, hUC-MSCs enhance the key factor in the activation of the PI3K/Akt pathway in T2DM mouse hepatocytes. CONCLUSION The pretreatment of hUC-MSCs with melatonin partly boosted cell efficiency and thereby alleviated impaired glycemic control and insulin resistance. This study provides a practical strategy to improve the application of hUC-MSCs in diabetes mellitus and cytotherapy. Overview of the PI3K/AKT signaling pathway. (A) Underlying mechanism of UCMSC/Mel inhibition of hyperglycemia and insulin resistance T2DM mice via regulation of PI3K/AKT pathway. hUC-MSCs stimulates glucose uptake and improves insulin action thus should inhibition the clinical signs of T2DM, through activation of the p-PI3K/Akt signaling pathway and then regulates glucose transport through activating AS160. UCMSC/Mel increases p53-dependent expression of BCL2, and inhibit BAX and Capase3 protein activation. Leading to the decrease in apoptosis. (B) Melatonin modulated PI3K/AKT signaling pathway. Melatonin activated PI3K/AKT response pathway through binding to MT1and MT2 receptor. Leading to the increase in hUC-MSCs proliferation, migration and differentiation. → (Direct stimulatory modification); ┴ ( Direct Inhibitory modification); → ┤ (Multistep inhibitory modification); ↑ (Up regulate); ↓ (Down regulate); PI3K (Phosphoinositide 3-Kinase); AKT ( protein kinase B); PDK1 (Phosphoinositide-dependent protein kinase 1); IR, insulin receptor; GLUT4 ( glucose transporter type 4); ROS (reactive oxygen species); BCL-2 (B-cell lymphoma-2); PDK1 (phosphoinositide-dependent kinase 1) BAX (B-cell lymphoma-2-associated X protein); PCNA (Proliferating cell nuclear antigen); Cell cycle-associated proteins (KI67, cyclin A, cyclin E).
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Affiliation(s)
- Aili Aierken
- College of Veterinary Medicine, Shaanxi Centre of Stem Cells Engineering and Technology, Northwest A&F University, YanglingShaanxi, 712100, China
| | - Balun Li
- College of Veterinary Medicine, Shaanxi Centre of Stem Cells Engineering and Technology, Northwest A&F University, YanglingShaanxi, 712100, China
| | - Peng Liu
- Department of Endocrinology and Metabolism, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China
| | - Xuedi Cheng
- College of Veterinary Medicine, Shaanxi Centre of Stem Cells Engineering and Technology, Northwest A&F University, YanglingShaanxi, 712100, China
| | - Zheng Kou
- College of Veterinary Medicine, Shaanxi Centre of Stem Cells Engineering and Technology, Northwest A&F University, YanglingShaanxi, 712100, China
| | - Ning Tan
- College of Veterinary Medicine, Shaanxi Centre of Stem Cells Engineering and Technology, Northwest A&F University, YanglingShaanxi, 712100, China
| | - Mengfei Zhang
- College of Veterinary Medicine, Shaanxi Centre of Stem Cells Engineering and Technology, Northwest A&F University, YanglingShaanxi, 712100, China
| | - Shuai Yu
- College of Veterinary Medicine, Shaanxi Centre of Stem Cells Engineering and Technology, Northwest A&F University, YanglingShaanxi, 712100, China
| | - Qiaoyan Shen
- College of Veterinary Medicine, Shaanxi Centre of Stem Cells Engineering and Technology, Northwest A&F University, YanglingShaanxi, 712100, China
| | - Xiaomin Du
- College of Veterinary Medicine, Shaanxi Centre of Stem Cells Engineering and Technology, Northwest A&F University, YanglingShaanxi, 712100, China
| | - Bold Bayar Enkhbaatar
- College of Veterinary Medicine, Shaanxi Centre of Stem Cells Engineering and Technology, Northwest A&F University, YanglingShaanxi, 712100, China
| | - Juqing Zhang
- College of Veterinary Medicine, Shaanxi Centre of Stem Cells Engineering and Technology, Northwest A&F University, YanglingShaanxi, 712100, China
| | - Rui Zhang
- College of Veterinary Medicine, Shaanxi Centre of Stem Cells Engineering and Technology, Northwest A&F University, YanglingShaanxi, 712100, China
| | - Xiaolong Wu
- College of Veterinary Medicine, Shaanxi Centre of Stem Cells Engineering and Technology, Northwest A&F University, YanglingShaanxi, 712100, China
| | - Ruibin Wang
- College of Veterinary Medicine, Shaanxi Centre of Stem Cells Engineering and Technology, Northwest A&F University, YanglingShaanxi, 712100, China
| | - Xin He
- College of Veterinary Medicine, Shaanxi Centre of Stem Cells Engineering and Technology, Northwest A&F University, YanglingShaanxi, 712100, China
| | - Na Li
- College of Veterinary Medicine, Shaanxi Centre of Stem Cells Engineering and Technology, Northwest A&F University, YanglingShaanxi, 712100, China
| | - Sha Peng
- College of Veterinary Medicine, Shaanxi Centre of Stem Cells Engineering and Technology, Northwest A&F University, YanglingShaanxi, 712100, China
| | - Wenwen Jia
- Institute for Regenerative Medicine, National Stem Cell Translational Resource Center, Shanghai East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, 200092, China.
| | - Congrong Wang
- Department of Endocrinology and Metabolism, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, 200434, China.
| | - Jinlian Hua
- College of Veterinary Medicine, Shaanxi Centre of Stem Cells Engineering and Technology, Northwest A&F University, YanglingShaanxi, 712100, China.
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17
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Arora S, Kanekiyo T, Singh J. Functionalized nanoparticles for brain targeted BDNF gene therapy to rescue Alzheimer's disease pathology in transgenic mouse model. Int J Biol Macromol 2022; 208:901-911. [PMID: 35378156 DOI: 10.1016/j.ijbiomac.2022.03.203] [Citation(s) in RCA: 36] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2022] [Revised: 03/08/2022] [Accepted: 03/29/2022] [Indexed: 12/11/2022]
Abstract
Brain-derived neurotrophic factor (BDNF) is actively produced and utilized in cortical circuits throughout life to sustain neuronal function and synaptic plasticity. In animal models of Alzheimer's Disease (AD), highly invasive BDNF gene therapy using viral vectors has successfully shown enhanced synaptic protein expression, proliferation of neurons and attenuation of amyloidogenic processes. However, to eliminate virus-related safety issues and invasive procedures, our present study has explored brain-targeted lipid-based nanoparticles that can deliver plasmid encoding BDNF to brain in a safe and efficient manner. Efficacy of these nanoparticles was tested in early (6-months) and advanced stage (9-months) transgenic APP/PS1 AD mice. Liposomes were surface-functionalized with brain targeting ligand, mannose, and cell-penetrating peptides (rabies virus-derived peptide or penetratin). These bifunctionalized nanoparticles enhanced BDNF expression by ~2 times and resulted in >40% (p < 0.05) reduction in toxic amyloid-beta peptides in 6- and 9-months old APP/PS1 mice brains compared to their age-matched untreated controls. Plaque load was reduced ~7 and ~3 times (p < 0.05), respectively, whereas synaptic proteins, synaptophysin and PSD-95, were found to be increased >90% (p < 0.05) in both age groups of transgenic mice treated with bifunctionalized nanoparticles. No untoward adverse effects were observed throughout treatment, suggesting a safe and effective strategy to rescue AD pathology.
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Affiliation(s)
- Sanjay Arora
- Department of Pharmaceutical Sciences, School of Pharmacy, College of Health Professions, North Dakota State University, Fargo, ND 58105, USA
| | - Takahisa Kanekiyo
- Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA
| | - Jagdish Singh
- Department of Pharmaceutical Sciences, School of Pharmacy, College of Health Professions, North Dakota State University, Fargo, ND 58105, USA.
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18
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Wu Z, Chen Y, Zhu D, Zheng Y, Ali KB, Hou K. Advancement of Traditional Chinese Medicine in Regulation of Intestinal Flora: Mechanism-based Role in Disease Management. Recent Pat Anticancer Drug Discov 2022; 17:136-144. [PMID: 34587887 DOI: 10.2174/1574892816666210929164930] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2021] [Revised: 04/19/2021] [Accepted: 04/22/2021] [Indexed: 02/05/2023]
Abstract
Intestinal microecology is the largest and most complex human microecology. The intestinal microflora plays an important role in human health. Imbalance of intestinal microflora contributes to the occurrence and development of many diseases. Recently, the treatment of human diseases by regulating intestinal microflora has become a research topic of interest. Traditional Chinese medicine considers the whole human body as the central concept in disease treatment strategies. It advocates maintaining the coordination and balance of the functions of various organs and systems of the human body, including the intestinal microflora. Traditional Chinese medicine improves the metabolism and immune function of the human body by regulating the intestinal microflora. The intestinal microflora could trigger pharmacological activity or reduce toxicity of drugs through regulating metabolism, which enables traditional Chinese medicine formulations to exert their best therapeutic effects. This review summarized the relationship between the intestinal microflora and digestive system, tumors, and other diseases. Furthermore, the role of traditional Chinese medicine in the treatment of tumors, and other diseases is discussed. The relationship among traditional Chinese medicine and the common intestinal microflora, pathogenesis of human diseases, and effective intervention methods were elaborated. In addition, we explored the research progress of traditional Chinese medicine in the treatment of various human diseases by regulating intestinal microflora to provide new treatment concepts. There is a close relationship between traditional Chinese medicine and the intestinal microflora. Traditional Chinese medicine formulations contribute to maintain the natural balance of the intestinal tract and the intestinal microflora to achieve treatment effects. This paper summarizes the mechanism of action of traditional Chinese medicine formulations in regulating the intestinal microflora in the prevention and treatment of various diseases. Furthermore, it summarizes information on the application of the interaction between traditional Chinese medicine preparations and the regulation of intestinal microflora in the treatment of common human diseases. Intestinal microflora plays a key role in traditional Chinese medicine in maintaining the natural balance of physiology and metabolism of human body. It will provide a theoretical basis for the traditional Chinese medicine preparations in the prevention and treatment of common human diseases, and simulate future research on this aspect.
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Affiliation(s)
- Zezhen Wu
- Department of Endocrine and Metabolic Diseases, Longhu Hospital, The First Affiliated Hospital of Medical College of Shantou University, Shantou City, Guangdong 515000, China and Graduate School, Shantou University Medical College, Shantou City, Guangdong 515000, China
- Graduate School, Shantou University Medical College, Shantou City, Guangdong, 515000, China
| | - Yongru Chen
- Department of Emergency Intensive Care Unit, The First Affiliated Hospital of Medical College of Shantou University, Shantou City, Guangdong, 515000, China
| | - Dan Zhu
- Department of Endocrine and Metabolic Diseases, Longhu Hospital, The First Affiliated Hospital of Medical College of Shantou University, Shantou City, Guangdong 515000, China and Graduate School, Shantou University Medical College, Shantou City, Guangdong 515000, China
| | - Yingmiao Zheng
- Department of Endocrine and Metabolic Diseases, Longhu Hospital, The First Affiliated Hospital of Medical College of Shantou University, Shantou City, Guangdong 515000, China and Graduate School, Shantou University Medical College, Shantou City, Guangdong 515000, China
| | - Khan Barkat Ali
- Faculty of Pharmacy, Gomal University, D.I. Khan, 29050, Pakistan
| | - Kaijian Hou
- Department of Endocrine and Metabolic Diseases, Longhu Hospital, The First Affiliated Hospital of Medical College of Shantou University, Shantou City, Guangdong 515000, China and Graduate School, Shantou University Medical College, Shantou City, Guangdong 515000, China
- Graduate School, Shantou University Medical College, Shantou City, Guangdong, 515000, China
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Roy P, Saha S, Chakraborty J. Looking into the possibilities of cure of the type 2 diabetes mellitus by nanoparticle-based RNAi and CRISPR-Cas9 system: A review. J Drug Deliv Sci Technol 2021. [DOI: 10.1016/j.jddst.2021.102830] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
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20
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Gong X, You L, Li F, Chen Q, Chen C, Zhang X, Zhang X, Xuan W, Sun K, Lao G, Wang C, Li Y, Xu M, Ren M, Yan L. The association of adiponectin with risk of pre-diabetes and diabetes in different subgroups: cluster analysis of a general population in south China. Endocr Connect 2021; 10:1410-1419. [PMID: 34612844 PMCID: PMC8630761 DOI: 10.1530/ec-21-0235] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/15/2021] [Accepted: 10/06/2021] [Indexed: 12/24/2022]
Abstract
OBJECTIVE Adiponectin is an adipocyte-derived hormone with an important role in glucose metabolism. The present study explored the effect of adiponectin in diverse population groups on pre-diabetes and newly diagnosed diabetes. METHODS A total of 3300 individuals were enrolled and their data were collected in the analyses dataset from December 2018 to October 2019. Cluster analysis was conducted based on age, BMI, waistline, body fat, systolic blood pressure, triglycerides, and glycosylated hemoglobin 1c. Cluster analysis divided the participants into four groups: a young-healthy group, an elderly-hypertension group, a high glucose-lipid group, and an obese group. Odds ratio (OR) and 95% CIs were calculated using multivariate logistic regression analysis. RESULTS Compared with the first quartile of adiponectin, the risk of pre-diabetes of fourth quartile was decreased 61% (aOR = 0.39, 95% CI (0.20-0.73)) in the young-healthy group; and the risk of diabetes of fourth quartile was decreased 85% (aOR = 0.15, 95% CI (0.02-0.67)) in the obese group. There were no significant correlations between the adiponectin level and diabetes/pre-diabetes in the other two groups. Additionally, receiver operating characteristic curve analysis indicated that adiponectin could significantly improve the diagnosis based on models in the young-healthy group (from 0.640 to 0.675) and the obese group (from 0.714 to 0.761). CONCLUSIONS Increased adiponectin levels were associated with decreased risk of pre-diabetes in the young-healthy population, and with a decreased the risk of diabetes in the obese population. An increased adiponectin level is an independent protective factor for pre-diabetes and diabetes in a specific population in south China.
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Affiliation(s)
- Xun Gong
- Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China
| | - Lili You
- Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China
| | - Feng Li
- Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China
| | - Qingyu Chen
- Department of Medical Examination Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China
| | - Chaogang Chen
- Department of Clinical Nutrition, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China
| | - Xiaoyun Zhang
- Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China
| | - Xiuwei Zhang
- Department of Endocrinology, Dongguan People’s Hospital, Dongguan, People’s Republic of China
| | - Wenting Xuan
- Department of Endocrinology, Dongguan People’s Hospital, Dongguan, People’s Republic of China
| | - Kan Sun
- Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China
| | - Guojuan Lao
- Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China
| | - Chuan Wang
- Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China
| | - Yan Li
- Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China
| | - Mingtong Xu
- Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China
| | - Meng Ren
- Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China
- Correspondence should be addressed to M Ren or L Yan: or
| | - Li Yan
- Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China
- Correspondence should be addressed to M Ren or L Yan: or
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Arora S, Sharma D, Layek B, Singh J. A Review of Brain-Targeted Nonviral Gene-Based Therapies for the Treatment of Alzheimer's Disease. Mol Pharm 2021; 18:4237-4255. [PMID: 34705472 DOI: 10.1021/acs.molpharmaceut.1c00611] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Diseases of the central nervous system (CNS) are difficult to treat owing to the complexity of the brain and the presence of a natural blood-brain-barrier (BBB). Alzheimer's disease (AD) is one of the major progressive and currently incurable neurodegenerative disorders of the CNS, which accounts for 60-80% of cases of dementia. The pathophysiology of AD involves the accumulation of amyloid beta (Aβ) plaques and neurofibrillary tangles (NFTs) in the brain. Additionally, synaptic loss and imbalance of neuronal signaling molecules are characterized as important markers of AD. Existing treatments of AD help in the management of its symptoms and aim toward the maintenance of cognitive functions, behavior, and attenuation of gradual memory loss. Over the past decade, nonviral gene therapy has attracted increasing interest due to its various advantages over its viral counterparts. Moreover, advancements in nonviral gene technology have led to their increasing contributions in clinical trials. However, brain-targeted nonviral gene delivery vectors come across various extracellular and intracellular barriers, limiting their ability to transfer the therapeutic gene into the target cells. Chief barriers to nonviral gene therapy have been discussed briefly in this review. We have also highlighted the rapid advancement of several nonviral gene therapies for AD, which are broadly categorized into physical and chemical methods. These methods aim to modulate Aβ, beta-site amyloid precursor protein (APP) cleaving enzyme 1 (BACE1), apolipoprotein E, or neurotrophic factors' expression in the CNS. Overall, this review discusses challenges and recent advancements of nonviral gene therapy for AD.
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Affiliation(s)
- Sanjay Arora
- Department of Pharmaceutical Sciences, School of Pharmacy, College of Health Professions, North Dakota State University, Fargo, North Dakota 58105, United States
| | - Divya Sharma
- Department of Pharmaceutical Sciences, School of Pharmacy, College of Health Professions, North Dakota State University, Fargo, North Dakota 58105, United States
| | - Buddhadev Layek
- Department of Pharmaceutical Sciences, School of Pharmacy, College of Health Professions, North Dakota State University, Fargo, North Dakota 58105, United States
| | - Jagdish Singh
- Department of Pharmaceutical Sciences, School of Pharmacy, College of Health Professions, North Dakota State University, Fargo, North Dakota 58105, United States
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22
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Arora S, Singh J. In vitro and in vivo optimization of liposomal nanoparticles based brain targeted vgf gene therapy. Int J Pharm 2021; 608:121095. [PMID: 34543617 PMCID: PMC8574129 DOI: 10.1016/j.ijpharm.2021.121095] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2021] [Revised: 08/30/2021] [Accepted: 09/12/2021] [Indexed: 12/14/2022]
Abstract
Vgf (non-acronymic), a neurotrophin stimulated protein which plays a crucial role in learning, synaptic activity, and neurogenesis, is markedly downregulated in the brain of Alzheimer's disease (AD) patients. However, since vgf is a large polar protein, a safe and efficient gene delivery vector is critical for its delivery across the blood brain barrier (BBB). This research work demonstrates brain-targeted liposomal nanoparticles optimized for delivering plasmid encoding vgf across BBB and transfecting brain cells. Brain targeting was achieved by surface functionalization using glucose transporter-1 targeting ligand (mannose) and brain targeted cell-penetrating peptides (chimeric rabies virus glycoprotein fragment, rabies virus derived peptide, penetratin peptide, or CGNHPHLAKYNGT peptide). The ligands were conjugated to lipid via nucleophilic substitution reaction resulting in >75% binding efficiency. The liposomes were formed by film hydration technique demonstrating size <200 nm, positive zeta potential (15-20 mV), and polydispersity index <0.3. The bifunctionalized liposomes demonstrated ∼3 pg/µg protein vgf transfection across in vitro BBB, and ∼80 pg/mg protein in mice brain which was 1.5-2 fold (p < 0.05) higher compared to untreated control. The nanoparticles were also biocompatible in vitro and in vivo, suggesting a safe and efficient gene delivery system to treat AD.
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Affiliation(s)
- Sanjay Arora
- Department of Pharmaceutical Sciences, School of Pharmacy, College of Health Professions, North Dakota State University, Fargo 58105, ND, USA
| | - Jagdish Singh
- Department of Pharmaceutical Sciences, School of Pharmacy, College of Health Professions, North Dakota State University, Fargo 58105, ND, USA.
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Sharma D, Arora S, Singh J, Layek B. A review of the tortuous path of nonviral gene delivery and recent progress. Int J Biol Macromol 2021; 183:2055-2073. [PMID: 34087309 PMCID: PMC8266766 DOI: 10.1016/j.ijbiomac.2021.05.192] [Citation(s) in RCA: 41] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2021] [Revised: 05/24/2021] [Accepted: 05/28/2021] [Indexed: 02/06/2023]
Abstract
Gene therapy encompasses the transfer of exogenous genetic materials into the patient's target cells to treat or prevent diseases. Nevertheless, the transfer of genetic material into desired cells is challenging and often requires specialized tools or delivery systems. For the past 40 years, scientists are mainly pursuing various viruses as gene delivery vectors, and the overall progress has been slow and far from the expectation. As an alternative, nonviral vectors have gained substantial attention due to their several advantages, including superior safety profile, enhanced payload capacity, and stealth abilities. Since nonviral vectors encounter multiple extra- and intra-cellular barriers limiting the transfer of genetic payload into the target cell nucleus, we have discussed these barriers in detail for this review. A direct approach, utilizing physical methods like electroporation, sonoporation, gene gun, eliminate the requirement for a specific carrier for gene delivery. In contrast, chemical methods of gene transfer exploit natural or synthetic compounds as carriers to increase cellular targeting and gene therapy effectiveness. We have also emphasized the recent advancements aimed at enhancing the current nonviral approaches. Therefore, in this review, we have focused on discussing the current evolving state of nonviral gene delivery systems and their future perspectives.
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Affiliation(s)
- Divya Sharma
- Department of Pharmaceutical Sciences, School of Pharmacy, College of Health Professions, North Dakota State University, Fargo 58105, ND, USA
| | - Sanjay Arora
- Department of Pharmaceutical Sciences, School of Pharmacy, College of Health Professions, North Dakota State University, Fargo 58105, ND, USA
| | - Jagdish Singh
- Department of Pharmaceutical Sciences, School of Pharmacy, College of Health Professions, North Dakota State University, Fargo 58105, ND, USA
| | - Buddhadev Layek
- Department of Pharmaceutical Sciences, School of Pharmacy, College of Health Professions, North Dakota State University, Fargo 58105, ND, USA.
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Qi R, Han X, Wang J, Qiu X, Wang Q, Yang F. MicroRNA-489-3p promotes adipogenesis by targeting the Postn gene in 3T3-L1 preadipocytes. Life Sci 2021; 278:119620. [PMID: 34004251 DOI: 10.1016/j.lfs.2021.119620] [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: 04/06/2021] [Revised: 05/07/2021] [Accepted: 05/10/2021] [Indexed: 12/11/2022]
Abstract
AIMS Accumulating evidence indicates that a number of microRNAs (miRNAs) serve as essential regulators during adipogenesis and adipolysis in humans and animals and play critical roles in the development of fat tissue. In this study, we aimed to determine the functional role and underlying regulatory mechanism of microRNA-489-3p (miR-489) in adipocytes. MATERIALS AND METHODS The expression patterns of miR-489 in mice were measured by qRT-PCR. Overexpression and knockdown of miR-489 by mimic and inhibitor transfections in 3T3-L1 preadipocytes revealed the regulatory effect of miR-489 on cellular proliferation and differentiation and energy turnover. Furthermore, RNA-seq, bioinformatics prediction, and dual luciferase reporter assays were used to identify the direct target of miR-489. KEY FINDINGS The results showed that miR-489 was highly expressed in the visceral fat tissue of adult mice, and obese mice exhibited higher levels of miR-489 than normal mice. Overexpression of miR-489 suppressed proliferation but promoted adipogenic differentiation and lipid accumulation in the cells. Mitochondrial oxidation also fluctuated in the cells due to the high expression of miR-489. Notably, knockdown of miR-489 did not have a strong opposing effect on the cells. Periostin (Postn) was identified as a direct target gene for miR-489, and silencing the Postn gene similarly stimulated adipogenesis and differentiation of adipocytes. SIGNIFICANCE miR-489 provides a strong driving force for adipogenesis metabolism and adipocyte differentiation by targeting the Postn gene. This result may contribute to the treatment of obesity.
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Affiliation(s)
- Renli Qi
- Chongqing Academy of Animal Science, Rongchang 402460, China; Chongqing Key Laboratory of Pig Industry Sciences, Rongchang 402460, China
| | - Xu Han
- ChaoYang Teachers College, Liaoning 122000, China
| | - Jing Wang
- Chongqing Academy of Animal Science, Rongchang 402460, China
| | - Xiaoyu Qiu
- Chongqing Academy of Animal Science, Rongchang 402460, China
| | - Qi Wang
- Chongqing Academy of Animal Science, Rongchang 402460, China
| | - Feiyun Yang
- Chongqing Academy of Animal Science, Rongchang 402460, China; Chongqing Key Laboratory of Pig Industry Sciences, Rongchang 402460, China.
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da Silva Rosa SC, Liu M, Sweeney G. Adiponectin Synthesis, Secretion and Extravasation from Circulation to Interstitial Space. Physiology (Bethesda) 2021; 36:134-149. [PMID: 33904786 PMCID: PMC8461789 DOI: 10.1152/physiol.00031.2020] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Adiponectin, an adipokine that circulates as multiple multimeric complexes at high levels in serum, has antidiabetic, anti-inflammatory, antiatherogenic, and cardioprotective properties. Understanding the mechanisms regulating adiponectin's physiological effects is likely to provide critical insight into the development of adiponectin-based therapeutics to treat various metabolic-related diseases. In this review, we summarize our current understanding on adiponectin action in its various target tissues and in cellular models. We also focus on recent advances in two particular regulatory aspects; namely, the regulation of adiponectin gene expression, multimerization, and secretion, as well as extravasation of circulating adiponectin to the interstitial space and its degradation. Finally, we discuss some potential therapeutic approaches using adiponectin as a target and the current challenges facing adiponectin-based therapeutic interventions.
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Affiliation(s)
| | - Meilian Liu
- Department of Biochemistry and Molecular Biology, University of New Mexico Health Sciences Center, Albuquerque, New Mexico
| | - Gary Sweeney
- Department of Biology, York University, Toronto, Ontario, Canada
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26
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Recent advances in peptide-targeted micelleplexes: Current developments and future perspectives. Int J Pharm 2021; 597:120362. [PMID: 33556489 DOI: 10.1016/j.ijpharm.2021.120362] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2020] [Revised: 01/27/2021] [Accepted: 02/03/2021] [Indexed: 12/11/2022]
Abstract
The decoding of the human genome revolutionized the understanding of how genetics influence the interplay between health and disease, in a multidisciplinary perspective. Thus, the development of exogenous nucleic acids-based therapies has increased to overcome hereditary or acquired genetic-associated diseases. Gene drug delivery using non-viral systems, for instance micelleplexes, have been recognized as promising options for gene-target therapies. Micelleplexes are core-shell structures, at a nanometric scale, designed using amphiphilic block copolymers. These can self-assemble in an aqueous medium, leading to the formation of a hydrophilic and positively charged corona - that can transport nucleic acids, - and a hydrophobic core - which can transport poor water-soluble drugs. However, the performance of these types of carriers usually is hindered by several in vivo barriers. Fortunately, due to a significant amount of research, strategies to overcome these shortcomings emerged. With a wide range of structural features, good stability against proteolytic degradation, affordable characteristic, easy synthesis, low immunogenicity, among other advantages, peptides have increasingly gained popularity as target ligands for non-viral carriers. Hence, this review addresses the use of peptides with micelleplexes illustrating, through the analysis of in vitro and in vivo studies, the potential and future perspectives of this combination.
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Kulkarni N, Shinde SD, Jadhav GS, Adsare DR, Rao K, Kachhia M, Maingle M, Patil SP, Arya N, Sahu B. Peptide-Chitosan Engineered Scaffolds for Biomedical Applications. Bioconjug Chem 2021; 32:448-465. [PMID: 33656319 DOI: 10.1021/acs.bioconjchem.1c00014] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Peptides are signaling epitopes that control many vital biological events. Increased specificity, synthetic feasibility with concomitant lack of toxicity, and immunogenicity make this emerging class of biomolecules suitable for different applications including therapeutics, diagnostics, and biomedical engineering. Further, chitosan, a naturally occurring linear polymer composed of d-glucosamine and N-acetyl-d-glucosamine units, possesses anti-microbial, muco-adhesive, and hemostatic properties along with excellent biocompatibility. As a result, chitosan finds application in drug/gene delivery, tissue engineering, and bioimaging. Despite these applications, chitosan demonstrates limited cell adhesion and lacks biosignaling. Therefore, peptide-chitosan hybrids have emerged as a new class of biomaterial with improved biosignaling properties and cell adhesion properties. As a result, recent studies encompass increased application of peptide-chitosan hybrids as composites or conjugates in drug delivery, cell therapy, and tissue engineering and as anti-microbial material. This review discusses the recent investigations involving chitosan-peptide materials and uncovers various aspects of these interesting hybrid materials for biomedical applications.
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Sharma D, Arora S, Banerjee A, Singh J. Improved insulin sensitivity in obese-diabetic mice via chitosan Nanomicelles mediated silencing of pro-inflammatory Adipocytokines. NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE 2021; 33:102357. [PMID: 33460779 DOI: 10.1016/j.nano.2020.102357] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/20/2020] [Revised: 12/22/2020] [Accepted: 12/22/2020] [Indexed: 12/13/2022]
Abstract
Obesity induced chronic low-level inflammation is strongly associated with the development of insulin resistance and progression of type-2 diabetes. Systemic treatment with anti-inflammatory therapeutics requires high doses and is associated with serious adverse effects owing to generalized suppression of the immune system. Here we study localized knockdown of pro-inflammatory adipocytokines in adipose tissue macrophages (ATMs) and adipocytes using RNA interference for the treatment of insulin resistance. Chitosan nanomicelles conjugated to ATM and adipocyte targeting ligands were used to transfect short hairpin RNA (shRNA) against tumor necrosis factor-α (TNFα) and monocyte chemoattractant protein-1 (MCP-1). Subcutaneous administration of nanomicellar/pDNA polyplexes in obese-diabetic mice resulted in decreased concentration of pro-inflammatory cytokines TNFα, MCP-1, IL-6, and IL-1β along with increased concentration of insulin-sensitizing adipokine adiponectin. Downregulation of inflammatory cytokines resulted in improved insulin sensitivity and glucose tolerance for up to six-weeks following single dose, compared to untreated obese-diabetic mice.
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Affiliation(s)
- Divya Sharma
- Department of Pharmaceutical Sciences, School of Pharmacy, College of Health Professions, North Dakota State University, Fargo, ND, USA
| | - Sanjay Arora
- Department of Pharmaceutical Sciences, School of Pharmacy, College of Health Professions, North Dakota State University, Fargo, ND, USA
| | - Amrita Banerjee
- Department of Pharmaceutical Sciences, School of Pharmacy, College of Health Professions, North Dakota State University, Fargo, ND, USA
| | - Jagdish Singh
- Department of Pharmaceutical Sciences, School of Pharmacy, College of Health Professions, North Dakota State University, Fargo, ND, USA.
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Sohouli MH, Sharifi-Zahabi E, Lari A, Fatahi S, Shidfar F. The impact of low advanced glycation end products diet on obesity and related hormones: a systematic review and meta-analysis. Sci Rep 2020; 10:22194. [PMID: 33335235 PMCID: PMC7747626 DOI: 10.1038/s41598-020-79216-y] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2020] [Accepted: 11/18/2020] [Indexed: 12/14/2022] Open
Abstract
Several randomized clinical trials (RCTs) have investigated the effect of dietary advanced glycation end products (AGE) on obesity factors and related hormones in adults; results were conflicting. Therefore, a study was performed to assess the effect of low advanced glycation end products diet on obesity and related hormones. A comprehensive literature search without any limitation on language was conducted using the following bibliographical databases: Web of Science, Scopus, Ovid MEDLINE, Cochrane, and Embase up to October, 2019. From the eligible trials, 13 articles were selected for the systematic review and meta-analysis. Our systematic reviews and meta-analyses have shown a significant decrease in BMI (WMD: − 0.3 kg/m2; 95% CI: − 0.52, − 0.09, p = 0.005; I2 = 55.8%), weight (WMD: − 0.83 kg; 95% CI: − 1.55, − 0.10, p = 0.026; I2 = 67.0%), and leptin (WMD: − 19.85 ng/ml; 95% CI: − 29.88, − 9.82, p < 0.001; I2 = 81.8%) and an increase in adiponectin (WMD: 5.50 µg/ml; 95% CI: 1.33, 9.67, p = 0.010; I2 = 90.6%) levels after consumption of the low AGE diets compared to the high AGE diets. Also, the effect of intake of low AGE compared to high AGE diets was more pronounced in subgroup with duration > 8 weeks for the BMI and weight. Overall, according to our results, although low AGE diets appeared to be statistically significant in reducing the prevalence of obesity and chronic diseases compared to high consumption of dietary AGEs. But, no clinical significance was observed. Therefore, to confirm these results clinically, further prospective studies should be conducted in this regard. The study protocol was registered in the in International prospective register of systematic reviews (PROSPERO) database as CRD42020203734.
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Affiliation(s)
- Mohammad Hassan Sohouli
- Student Research Committee, Faculty of Public Health Branch, Iran University of Medical Sciences, Tehran, Iran.,Department of Nutrition, School of Public Health, Iran University of Medical Sciences, Hemmat Superhighway, Tehran, Iran
| | - Elham Sharifi-Zahabi
- Student Research Committee, Faculty of Public Health Branch, Iran University of Medical Sciences, Tehran, Iran.,Department of Nutrition, School of Public Health, Iran University of Medical Sciences, Hemmat Superhighway, Tehran, Iran
| | - Abolfazl Lari
- Student Research Committee, Faculty of Public Health Branch, Iran University of Medical Sciences, Tehran, Iran.,Department of Nutrition, School of Public Health, Iran University of Medical Sciences, Hemmat Superhighway, Tehran, Iran
| | - Somaye Fatahi
- Student Research Committee, Faculty of Public Health Branch, Iran University of Medical Sciences, Tehran, Iran.,Department of Nutrition, School of Public Health, Iran University of Medical Sciences, Hemmat Superhighway, Tehran, Iran
| | - Farzad Shidfar
- Student Research Committee, Faculty of Public Health Branch, Iran University of Medical Sciences, Tehran, Iran. .,Pediatric growth and development research center, Iran University of Medical Sciences, Tehran, Iran.
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Scopolin Prevents Adipocyte Differentiation in 3T3-L1 Preadipocytes and Weight Gain in an Ovariectomy-Induced Obese Mouse Model. Int J Mol Sci 2020; 21:ijms21228699. [PMID: 33218042 PMCID: PMC7698923 DOI: 10.3390/ijms21228699] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2020] [Accepted: 11/16/2020] [Indexed: 02/06/2023] Open
Abstract
Obesity is prevalent in modern human societies. We examined the anti-obesity effects of scopolin on adipocyte differentiation in preadipocyte 3T3-L1 cells and weight loss in an ovariectomy (OVX)-induced obese mouse model. Scopolin inhibited adipocyte differentiation and lipid accumulation in the preadipocyte cells by suppressing the transcription of adipogenic-related factors, including adiponectin (Adipoq), peroxisome proliferator-activated receptor gamma (Pparg), lipoprotein lipase (Lpl), perilipin1 (Plin1), fatty acid-binding protein 4 (Fabp4), glucose transporter type 4 (Slc2a4), and CCAAT/enhancer-binding protein alpha (Cebpa). In OVX-induced obese mice, administration of scopolin promoted the reduction of body weight, total fat percentage, liver steatosis, and adipose cell size. In addition, the scopolin-treated OVX mice showed decreased serum levels of leptin and insulin. Taken together, these findings suggest that the use of scopolin prevented adipocyte differentiation and weight gain in vitro and in vivo, indicating that scopolin may be a potential bioactive compound for the treatment and prevention of obesity in humans.
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Francischetti EA, Dezonne RS, Pereira CM, de Moraes Martins CJ, Celoria BMJ, de Oliveira PAC, de Abreu VG. Insights Into the Controversial Aspects of Adiponectin in Cardiometabolic Disorders. Horm Metab Res 2020; 52:695-707. [PMID: 32927496 DOI: 10.1055/a-1239-4349] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
In 2016, the World Health Organization estimated that more than 1.9 billion adults were overweight or obese. This impressive number shows that weight excess is pandemic. Overweight and obesity are closely associated with a high risk of comorbidities, such as insulin resistance and its most important outcomes, including metabolic syndrome, type 2 diabetes mellitus, and cardiovascular disease. Adiponectin has emerged as a salutary adipocytokine, with insulin-sensitizing, anti-inflammatory, and cardiovascular protective properties. However, under metabolically unfavorable conditions, visceral adipose tissue-derived inflammatory cytokines might reduce the transcription of the adiponectin gene and consequently its circulating levels. Low circulating levels of adiponectin are negatively associated with various conditions, such as insulin resistance, type 2 diabetes mellitus, metabolic syndrome, and cardiovascular disease. In contrast, several recent clinical trials and meta-analyses have reported high circulating adiponectin levels positively associated with cardiovascular mortality and all-cause mortality. These results are biologically intriguing and counterintuitive, and came to be termed "the adiponectin paradox". Adiponectin paradox is frequently associated with adiponectin resistance, a concept related with the downregulation of adiponectin receptors in insulin-resistant states. We review this contradiction between the apparent role of adiponectin as a health promoter and the recent evidence from Mendelian randomization studies indicating that circulating adiponectin levels are an unexpected predictor of increased morbidity and mortality rates in several clinical conditions. We also critically review the therapeutic perspective of synthetic peptide adiponectin receptors agonist that has been postulated as a promising alternative for the treatment of metabolic syndrome and type 2 diabetes mellitus.
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Affiliation(s)
- Emilio Antonio Francischetti
- Laboratory of Clinical and Experimental Pathophysiology, Rio de Janeiro State University, Rio de Janeiro, Brazil
| | - Rômulo Sperduto Dezonne
- Postgraduate Program in Translational Biomedicine, Grande Rio University, Duque de Caxias, Brazil
| | - Cláudia Maria Pereira
- Postgraduate Program in Translational Biomedicine, Grande Rio University, Duque de Caxias, Brazil
| | - Cyro José de Moraes Martins
- Laboratory of Clinical and Experimental Pathophysiology, Rio de Janeiro State University, Rio de Janeiro, Brazil
| | | | | | - Virgínia Genelhu de Abreu
- Laboratory of Clinical and Experimental Pathophysiology, Rio de Janeiro State University, Rio de Janeiro, Brazil
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