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Yu M, Ning FTE, Liu C, Liu YC. Interconnections between diabetic corneal neuropathy and diabetic retinopathy: diagnostic and therapeutic implications. Neural Regen Res 2025; 20:2169-2180. [PMID: 39359077 PMCID: PMC11759029 DOI: 10.4103/nrr.nrr-d-24-00509] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2024] [Revised: 06/28/2024] [Accepted: 07/24/2024] [Indexed: 10/04/2024] Open
Abstract
Diabetic corneal neuropathy and diabetic retinopathy are ocular complications occurring in the context of diabetes mellitus. Diabetic corneal neuropathy refers to the progressive damage of corneal nerves. Diabetic retinopathy has traditionally been considered as damage to the retinal microvasculature. However, growing evidence suggests that diabetic retinopathy is a complex neurovascular disorder resulting from dysfunction of the neurovascular unit, which includes both the retinal vascular structures and neural tissues. Diabetic retinopathy is one of the leading causes of blindness and is frequently screened for as part of diabetic ocular screening. However, diabetic corneal neuropathy is commonly overlooked and underdiagnosed, leading to severe ocular surface impairment. Several studies have found that these two conditions tend to occur together, and they share similarities in their pathogenesis pathways, being triggered by a status of chronic hyperglycemia. This review aims to discuss the interconnection between diabetic corneal neuropathy and diabetic retinopathy, whether diabetic corneal neuropathy precedes diabetic retinopathy, as well as the relation between the stage of diabetic retinopathy and the severity of corneal neuropathy. We also endeavor to explore the relevance of a corneal screening in diabetic eyes and the possibility of using corneal nerve measurements to monitor the progression of diabetic retinopathy.
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Affiliation(s)
- Mingyi Yu
- Tissue Engineering and Stem Cell Group, Singapore Eye Research Institute, Singapore
| | - Faith Teo En Ning
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Chang Liu
- Tissue Engineering and Stem Cell Group, Singapore Eye Research Institute, Singapore
| | - Yu-Chi Liu
- Tissue Engineering and Stem Cell Group, Singapore Eye Research Institute, Singapore
- Department of Cornea and External Eye Disease, Singapore National Eye Center, Singapore
- Ophthalmology and Visual Sciences Academic Clinical Program, Duke-NUS Medical School, Singapore
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Shinouchi R, Shibata K, Nagatsuka T, Hasumi K, Nobe K. Antioxidant and anti-inflammatory effects of SMTP-44D in a streptozotocin-induced diabetic neuropathy mouse model. J Diabetes Complications 2025; 39:109061. [PMID: 40318460 DOI: 10.1016/j.jdiacomp.2025.109061] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2025] [Revised: 03/14/2025] [Accepted: 04/27/2025] [Indexed: 05/07/2025]
Abstract
BACKGROUND Diabetic neuropathy (DN) is a debilitating complication of diabetes, driven by oxidative stress, inflammation, and advanced glycation end products (AGE) signaling through its receptor (RAGE). Soluble epoxide hydrolase (sEH) metabolizes anti-inflammatory epoxyeicosatrienoic acids (EETs) into pro-inflammatory dihydroxyeicosatrienoic acids (DHETs), exacerbating DN pathology. SMTP-44D, an sEH inhibitor, has demonstrated antioxidant and anti-inflammatory effects in vitro; however, its in vivo efficacy remains unclear. AIM To investigate the antioxidant and anti-inflammatory activities of SMTP-44D in relation to sEH inhibition and AGE/RAGE signaling in a streptozotocin (STZ)-induced DN mouse model. METHODOLOGY STZ-induced diabetic mice were treated with SMTP-44D (30 mg/kg) from days 8 to 28 post STZ injection (200 mg/kg). Oxidative stress markers, inflammatory factors, AGE in the sciatic nerve, and RAGE in serum were assessed via ELISA. DHET levels in serum were measured using LC-MS/MS, and apoptosis in the sciatic nerve was assessed via TUNEL staining and fluorescent immunohistochemistry for cleaved caspase-3. RESULTS Our findings indicated that SMTP-44D inhibited sEH, reducing DHET levels and sustaining anti-inflammatory effects. It attenuated the migration of nuclear factor-kappa B, decreased AGE and RAGE levels, and suppressed oxidative stress and inflammatory markers in the sciatic nerve. Moreover, SMTP-44D inhibited apoptosis, potentially mitigating the axonal damage associated with DN. CONCLUSION Our findings suggest that SMTP-44D is a promising therapeutic agent for DN, acting through sEH inhibition and reducing AGE/RAGE levels.
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Affiliation(s)
- Ryosuke Shinouchi
- Department of Pharmacology, Showa Medical University Graduate School of Pharmacy (R.S.; K.S.; K.N.), 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan; Pharmacological Research Center, Showa Medical University (R.S.; K.S.; K.N.), 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan.
| | - Keita Shibata
- Department of Pharmacology, Showa Medical University Graduate School of Pharmacy (R.S.; K.S.; K.N.), 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan; Pharmacological Research Center, Showa Medical University (R.S.; K.S.; K.N.), 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan
| | - Taiju Nagatsuka
- Division of Pharmacology, Department of Pharmacology, Toxicology and Therapeutics, School of Pharmacy, Showa Medical University (T.N.), 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan
| | - Keiji Hasumi
- Department of Applied Biological Science, Tokyo University of Agriculture and Technology (K.H.), 3-5-8 Saiwaicho, Fuchu-shi, Tokyo 183-8509, Japan; TMS Co., Ltd. (K.H.), 1-9-11F Fuchucho, Fuchu-shi, Tokyo 183-0055, Japan
| | - Koji Nobe
- Department of Pharmacology, Showa Medical University Graduate School of Pharmacy (R.S.; K.S.; K.N.), 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan; Pharmacological Research Center, Showa Medical University (R.S.; K.S.; K.N.), 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan
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Kamboj SS, Sharma SP, Mohamed WM, Sandhir R. N-acetyl-L-cysteine mitigates diabetes-induced impairments in sciatic nerve. IBRO Neurosci Rep 2025; 18:512-519. [PMID: 40177701 PMCID: PMC11964552 DOI: 10.1016/j.ibneur.2025.02.006] [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: 08/27/2024] [Revised: 02/14/2025] [Accepted: 02/15/2025] [Indexed: 04/05/2025] Open
Abstract
Diabetic neuropathy is a consequence of long-term hyperglycemia. The emergence of neuronal condition is a result of hyperglycemia-induced oxidative stress. In the present study, streptozotocin-induced diabetes exhibited notable decrease in the levels of phospholipids, glycolipids, gangliosides, and triglycerides in the sciatic nerve. The alterations in lipids resulted in increase in cholesterol to phospholipid ratio in sciatic nerve of diabetic animals. This ratio is crucial and determines the rheological properties of membranes and resulted in substantial reduction in the activity of membrane-bound enzymes; Ca2 + ATPase and acetylcholinesterase. Histological examination of the cross-section of the sciatic nerve in diabetic mice revealed axonal atrophy and disarrayed myelin sheath. The potential therapeutic impact of N-acetyl Cysteine (NAC), a powerful antioxidant, on a rat model of diabetic neuropathy was evaluated. NAC was administered to rats in drinking water for a period of 8 weeks. The results indicate that administration of NAC restored lipid composition; ratio of cholesterol to phospholipids, the activity of membrane linked enzymes, and improved the structural defects in sciatic nerve. NAC plays protective role against diabetes-induced alterations in lipid composition in sciatic nerve membranes leading to improvement in structure and function of membranes. Overall, the findings suggest NAC as a potential therapeutic strategy in preventing diabetic neuropathy and other diabetic complications.
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Affiliation(s)
- Sukhdev S. Kamboj
- Department of Biochemistry, Basic Medical Science Block II, Panjab University, Chandigarh 160014, India
| | - Satya P. Sharma
- Department of Biochemistry, Basic Medical Science Block II, Panjab University, Chandigarh 160014, India
| | - Wael M.Y. Mohamed
- Department of Basic Medical Sciences, International Islamic University Malaysia, Kuala Lumpur 50728, Malaysia
| | - Rajat Sandhir
- Department of Biochemistry, Basic Medical Science Block II, Panjab University, Chandigarh 160014, India
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Naeimi Ghahroodi MH, Bahari Z, Mashhadi Akbar Boojar M. Comparative analysis of analgesic and anxiolytic effects of alcoholic extracts from Eryngium billardieri and Urtica dioica in a rat model of chronic pain. Behav Brain Res 2025; 485:115537. [PMID: 40086636 DOI: 10.1016/j.bbr.2025.115537] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2024] [Revised: 03/06/2025] [Accepted: 03/09/2025] [Indexed: 03/16/2025]
Abstract
OBJECTIVE The treatment of neuropathic pain is crucial, as it not only alleviates physical discomfort but also reduces anxiety associated with pain, ultimately enhancing the quality of life for affected individuals. This study investigates the protective effects of hydro-alcoholic extracts from Eryngium billardieri (Er) and Urtica dioica (Ur) on neuropathic pain and anxiety responses in an animal model. METHODS 40 male Wistar rats were used to investigate neuropathy induced by the chronic constriction injury (CCI) model. Animals were divided into five experimental groups (N = 8): [sham], [CCI], [CCI+Er], [CCI+Ur], and [CCI+Imipramine]. Er and Ur were administered orally for 30 days, starting on the day of surgery. Behavioral tests, including acetone for cold allodynia, the elevated plus maze for anxiety-like behaviors, and the open field for innate anxiety, were conducted on day -1 (before CCI) and on days 2, 4, 6, 14, 21, and 30. Data were analyzed by one-way analysis of variance test, and P < 0.05 was considered significant. RESULTS Neuropathic surgery resulted in cold allodynia and anxiety-like behaviors throughout the experiment as compared to the sham. Er extract significantly decreased both cold allodynia and anxiety-like behaviors in the CCI group. However, Ur extract only significantly reduced cold allodynia (and not anxiety-like behaviors). Additionally, there was no difference between the analgesic effects of Er and Ur extracts. CONCLUSIONS These findings support the use of Er as a potential comprehensive treatment for neuropathic pain and anxiety symptoms. Future research should focus on exploring the specific mechanisms behind these effects and the potential for synergistic treatments to improve outcomes for individuals suffering from neuropathy.
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Affiliation(s)
| | - Zahra Bahari
- Department of Physiology and Biophysics, Faculty of Medicine, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Mahdi Mashhadi Akbar Boojar
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Baqiyatallah University of Medical Sciences, Tehran, Iran.
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Lutz M, Arancibia M, Moran-Kneer J, Manterola M. Ultraprocessed Foods and Neuropsychiatric Outcomes: Putative Mechanisms. Nutrients 2025; 17:1215. [PMID: 40218973 PMCID: PMC11990412 DOI: 10.3390/nu17071215] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2025] [Revised: 03/21/2025] [Accepted: 03/26/2025] [Indexed: 04/14/2025] Open
Abstract
A body of evidence indicates an association between ultraprocessed foods (UPFs) and health outcomes. Most of it has been obtained through preclinical studies, although a number of observational studies substantiate how a high intake of these products increases the risk of neuropsychiatric disorders, and an increasing amount of dietary intervention studies confirm these findings. The aim of this narrative review is to describe some of the putative mechanisms involved in the deleterious effects of a high intake of UPFs on neuropsychiatric outcomes. A myriad of unhealthy actions may be associated with the consumption of UPFs, and some mechanisms are being discussed. They include UPFs' high caloric density; their high sugar, sodium, and additives content and low amounts of fiber; and a high palatability that induces overconsumption, acting as obesogens. Moreover, thermal treatment of these foods generates oxidative products such as glycotoxins, lipotoxins, and acrolein, all of which affect the brain. The chemical products act, directly or indirectly, on the gut microbiome and affect the gut-brain axis, causing neuroinflammation, oxidative stress, and neurodegeneration. UPFs also exert various epigenetic effects that affect mental health and might explain the intergenerational inheritance of neuropsychiatric disorders. A diet containing a high proportion of these foods has a low nutritional density, including bioactive protective agents such as antioxidant and anti-inflammatory compounds that promote eubiosis. The evidence shows that UPFs intake affects neuropsychiatric outcomes such as neurodegeneration, cognitive decline, dementia, and mood disorders and reinforces the need to promote a healthy dietary pattern throughout all life stages, thus interfering with the current commercial determinants of health.
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Affiliation(s)
- Mariane Lutz
- Center for Translational Studies in Stress and Mental Health (C-ESTRES), Universidad de Valparaíso, Valparaíso 2360102, Chile; (M.A.); (J.M.-K.); (M.M.)
- School of Medicine, Faculty of Medicine, Universidad de Valparaíso, Viña del Mar 2520000, Chile
| | - Marcelo Arancibia
- Center for Translational Studies in Stress and Mental Health (C-ESTRES), Universidad de Valparaíso, Valparaíso 2360102, Chile; (M.A.); (J.M.-K.); (M.M.)
- School of Medicine, Faculty of Medicine, Universidad de Valparaíso, Viña del Mar 2520000, Chile
| | - Javier Moran-Kneer
- Center for Translational Studies in Stress and Mental Health (C-ESTRES), Universidad de Valparaíso, Valparaíso 2360102, Chile; (M.A.); (J.M.-K.); (M.M.)
- School of Psychology, Faculty of Social Sciences, Universidad de Valparaíso, Valparaíso 2340000, Chile
| | - Marcia Manterola
- Center for Translational Studies in Stress and Mental Health (C-ESTRES), Universidad de Valparaíso, Valparaíso 2360102, Chile; (M.A.); (J.M.-K.); (M.M.)
- Human Genetics Program, Institute of Biomedical Sciences, Faculty of Medicine, Universidad de Chile, Santiago 8380453, Chile
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Yuan X, Li Y, Cong L, Yang L, Zhang Y, Zhang Z, Wang T, Dong M, Du X, Xie L, Zhou Q. Norepinephrine regulates epithelial-derived neurotrophins expression and sensory nerve regeneration through ADRB2 receptor. Commun Biol 2025; 8:481. [PMID: 40121310 PMCID: PMC11929770 DOI: 10.1038/s42003-025-07903-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2024] [Accepted: 03/07/2025] [Indexed: 03/25/2025] Open
Abstract
Norepinephrine (NE) is mainly released by sympathetic nerve terminals to act on organs and tissues. After corneal epithelial debridement, we found that the sympathetic nerve fibers penetrated the limbus and regenerated toward the cornea within 24 h post-wounding. Topical NE application recapitulated the characteristics of delayed corneal epithelial wound healing and nerve regeneration in healthy mice, accompanied by the partial depletion of multiple neurotrophins, such as nerve growth factor and glial cell-derived nerve growth factor. Moreover, the diabetes mellitus (DM) mice exhibited corneal sensory nerve dysfunction and increased plasma and corneal NE contents, which were rescued by 6-hydroxydopamine (6-OHDA) and bretylium. In the cell culture model, the conditioned medium of NE-treated corneal epithelial cells inhibited trigeminal ganglion (TG) neurite outgrowth, which was reversed by the β2 adrenergic receptor (ADRB2) antagonist, but not by the β1 adrenergic receptor (ADRB1) antagonist. Topical application of the ADRB2 antagonist recovered the expression of corneal neurotrophins, and promoted corneal epithelial and nerve regeneration in DM mice. Taken together, the NE-ADRB2 axis regulates corneal neurotrophin expression and nerve regeneration in mice. Topical application of the ADRB2 antagonist may represent a promising therapeutic strategy for diabetic corneal sensory nerve dysfunction.
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Affiliation(s)
- Xingyue Yuan
- State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Eye Institute of Shandong First Medical University, Qingdao, 266071, China
- Qingdao Eye Hospital of Shandong First Medical University, Qingdao, 266071, China
- Department of Pathology, Deyang People's Hospital, Deyang, 618000, China
| | - Ya Li
- State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Eye Institute of Shandong First Medical University, Qingdao, 266071, China
- Qingdao Eye Hospital of Shandong First Medical University, Qingdao, 266071, China
| | - Lin Cong
- State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Eye Institute of Shandong First Medical University, Qingdao, 266071, China
- Qingdao Eye Hospital of Shandong First Medical University, Qingdao, 266071, China
| | - Lingling Yang
- State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Eye Institute of Shandong First Medical University, Qingdao, 266071, China
- Qingdao Eye Hospital of Shandong First Medical University, Qingdao, 266071, China
| | - Yangyang Zhang
- State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Eye Institute of Shandong First Medical University, Qingdao, 266071, China
- Qingdao Eye Hospital of Shandong First Medical University, Qingdao, 266071, China
| | - Zhenzhen Zhang
- State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Eye Institute of Shandong First Medical University, Qingdao, 266071, China
- Qingdao Eye Hospital of Shandong First Medical University, Qingdao, 266071, China
| | - Ting Wang
- State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Eye Institute of Shandong First Medical University, Qingdao, 266071, China
- Eye Hospital of Shandong First Medical University, Jinan, 250021, China
| | - Muchen Dong
- State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Eye Institute of Shandong First Medical University, Qingdao, 266071, China
- Eye Hospital of Shandong First Medical University, Jinan, 250021, China
| | - Xianli Du
- State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Eye Institute of Shandong First Medical University, Qingdao, 266071, China
- Qingdao Eye Hospital of Shandong First Medical University, Qingdao, 266071, China
| | - Lixin Xie
- State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Eye Institute of Shandong First Medical University, Qingdao, 266071, China
- Qingdao Eye Hospital of Shandong First Medical University, Qingdao, 266071, China
| | - Qingjun Zhou
- State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Eye Institute of Shandong First Medical University, Qingdao, 266071, China.
- Qingdao Eye Hospital of Shandong First Medical University, Qingdao, 266071, China.
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Arı M, Erdogan MA, Erbaş O. Investigation of the protective effects of dichloroacetic acid in a rat model of diabetic neuropathy. BMC Pharmacol Toxicol 2025; 26:15. [PMID: 39844306 PMCID: PMC11756200 DOI: 10.1186/s40360-025-00849-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2024] [Accepted: 01/20/2025] [Indexed: 01/24/2025] Open
Abstract
BACKGROUND Diabetic neuropathy (DN) is a heterogeneous condition characterized by complex pathophysiological changes affecting both autonomic and somatic components of the nervous system. Inflammation and oxidative stress are recognized contributors to the pathogenesis of DN. This study aims to evaluate the therapeutic potential of dichloroacetic acid (DCA) in alleviating DN symptoms, focusing on its anti-inflammatory and antioxidant properties. METHODS Thirty-two adult male Sprague Dawley rats were divided into four groups: Control, Diabetic, and two DCA-treated groups receiving 5 mg/kg and 10 mg/kg of DCA, respectively. Diabetes was induced with streptozotocin (STZ) injections. Assessments included lipid peroxidation levels, plasma fibroblast growth factor-21 (FGF-21) and transforming growth factor-beta (TGF-β) levels, electrophysiological measurements, histological examination of the sciatic nerve, and motor function tests. RESULTS Treatment with DCA significantly reduced malondialdehyde (MDA) levels, indicating decreased lipid peroxidation. Plasma TGF-β levels were also lower in the DCA-treated groups, suggesting diminished inflammation. Conversely, plasma FGF-21 levels were elevated. Electrophysiological assessments revealed enhanced compound muscle action potential (CMAP) amplitudes and reduced distal latencies in DCA-treated rats, indicative of improved nerve conduction. Histopathological examinations showed reduced perineural thickness in the sciatic nerves of DCA-treated rats, pointing to decreased fibrosis. Enhanced performance in motor function tests was observed in these rats, implying improved muscle strength and motor capacity. CONCLUSIONS The study demonstrates that DCA therapy significantly reduces oxidative stress and inflammation in a rat model of DN, thereby ameliorating neuropathic symptoms. These results support the potential of DCA as a promising therapeutic agent for DN treatment. Further research is warranted to explore its clinical applications and to provide more detailed insights.
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Affiliation(s)
- Murat Arı
- Söke Health Services Vocational School, Aydin Adnan Menderes University, Aydin, Turkey.
| | - Mumin Alper Erdogan
- Faculty of Medicine, Department of Physiology, Izmir Katip Celebi University, Izmir, Turkey
| | - Oytun Erbaş
- Faculty of Medicine, Department of Physiology, Istanbul Demiroglu Bilim University, Istanbul, Turkey
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AbdRabou MA, Mehany ABM, Massoud D, Nabeeh A, Asran AM, Germoush MO, Al-Otaibi AM, Atwa A. Mitigation of biochemical alterations in streptozotocin-induced gestational diabetes in rats through mesenchymal stem cells and olive leaf extract. JOURNAL OF EXPERIMENTAL ZOOLOGY. PART A, ECOLOGICAL AND INTEGRATIVE PHYSIOLOGY 2025; 343:25-34. [PMID: 39233508 DOI: 10.1002/jez.2862] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/19/2024] [Revised: 07/28/2024] [Accepted: 07/31/2024] [Indexed: 09/06/2024]
Abstract
Treatment with mesenchymal stem cells (MSCs) is a new promising therapeutic approach with substantial very auspicious potential. They have been shown to protect various played a role in protecting organs from damage. This current study aims to evaluate the impact of the treatment of olive leaf extract (OLE), bone marrow-derived (BM-MSCs), and their combination on hepatotoxicity in pregnant rats with diabetes. METHODS Animals were divided into five groups (10 pregnant rats each) as follows: control, GDM group, and OLE group (rats received streptozotocin (STZ) at a dose of 35 mg/kg body weight). GD + OLE set (pregnant rats were administered OLE at a dose of 200 mg extract/kg of body weight). GD + MSCs group (pregnant rats treated with MSCs). GD + OLE + MSCs group (pregnant rats were treated with both MSCs and OLE). RESULTS STZ induced significant changes in liver parameters, lipid profile, and oxidative stress. Treatment with OLE, BM-MSCs, and their combination significantly ameliorated STZ-induced liver damage and oxidative stress. STZ resulted in a significant change in liver parameters, lipid profile, and oxidative stress. OLE, BM-MSC, and combination have significantly improved STZ-induced deterioration in liver and improved oxidative stress. CONCLUSIONS The findings demonstrate that OLE and BM-MSCs have beneficial effects in mitigating diabetes-related liver alterations. These outcomes showed that OLE and BM-MSC have beneficial effects in alleviating diabetes-related alterations in the liver.
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Affiliation(s)
- Mervat A AbdRabou
- Biology Department, College of Science, Olive Research Center, Jouf University, Sakaka, Saudi Arabia
| | - Ahmed B M Mehany
- Zoology Department, Faculty of Science (Boys), Al-Azhar University, Cairo, Egypt
| | - Diaa Massoud
- Biology Department, College of Science, Olive Research Center, Jouf University, Sakaka, Saudi Arabia
| | - Ahmed Nabeeh
- Zoology Department, Faculty of Science (Boys), Al-Azhar University, Cairo, Egypt
| | - Aml M Asran
- Olive Research Center, Jouf University, Dean of the common First Year, Sakaka, Saudi Arabia
| | - Mousa O Germoush
- Biology Department, College of Science, Olive Research Center, Jouf University, Sakaka, Saudi Arabia
| | - Aljohara M Al-Otaibi
- Department of Biology, College of Science, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia
| | - Ahmed Atwa
- Zoology Department, Faculty of Science (Boys), Al-Azhar University, Cairo, Egypt
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Lupu VV, Miron I, Trandafir LM, Jechel E, Starcea IM, Ioniuc I, Frasinariu OE, Mocanu A, Petrariu FD, Danielescu C, Nedelcu AH, Salaru DL, Revenco N, Lupu A. Challenging directions in pediatric diabetes - the place of oxidative stress and antioxidants in systemic decline. Front Pharmacol 2024; 15:1472670. [PMID: 39744134 PMCID: PMC11688324 DOI: 10.3389/fphar.2024.1472670] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2024] [Accepted: 12/04/2024] [Indexed: 01/06/2025] Open
Abstract
Diabetes is a complex condition with a rising global incidence, and its impact is equally evident in pediatric practice. Regardless of whether we are dealing with type 1 or type 2 diabetes, the development of complications following the onset of the disease is inevitable. Consequently, contemporary medicine must concentrate on understanding the pathophysiological mechanisms driving systemic decline and on finding ways to address them. We are particularly interested in the effects of oxidative stress on target cells and organs, such as pancreatic islets, the retina, kidneys, and the neurological or cardiovascular systems. Our goal is to explore, using the latest data from international scientific databases, the relationship between oxidative stress and the development or persistence of systemic damage associated with diabetes in children. Additionally, we highlight the beneficial roles of antioxidants such as vitamins, minerals, polyphenols, and other bioactive molecules; in mitigating the pathogenic cascade, detailing how they intervene and their bioactive properties. As a result, our study provides a comprehensive exploration of the key aspects of the oxidative stress-antioxidants-pediatric diabetes triad, expanding understanding of their significance in various systemic diseases.
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Affiliation(s)
- Vasile Valeriu Lupu
- Pediatrics, “Grigore T. Popa” University of Medicine and Pharmacy, Iasi, Romania
| | - Ingrith Miron
- Pediatrics, “Grigore T. Popa” University of Medicine and Pharmacy, Iasi, Romania
| | | | - Elena Jechel
- Pediatrics, “Grigore T. Popa” University of Medicine and Pharmacy, Iasi, Romania
| | | | - Ileana Ioniuc
- Pediatrics, “Grigore T. Popa” University of Medicine and Pharmacy, Iasi, Romania
| | | | - Adriana Mocanu
- Pediatrics, “Grigore T. Popa” University of Medicine and Pharmacy, Iasi, Romania
| | | | - Ciprian Danielescu
- Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, Iasi, Romania
| | - Alin Horatiu Nedelcu
- Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, Iasi, Romania
| | - Delia Lidia Salaru
- Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, Iasi, Romania
| | - Ninel Revenco
- Pediatrics, “Nicolae Testemitanu” State University of Medicine and Pharmacy, Chisinau, Moldova
| | - Ancuta Lupu
- Pediatrics, “Grigore T. Popa” University of Medicine and Pharmacy, Iasi, Romania
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Zhang W, Yan Y, Yi C, Jiang X, Guo L, Huang S, Xia T, Huang F, Jiao Y, Li H, Yu B, Dai Y. Targeting ferroptosis in the neurovascular unit: A promising approach for treating diabetic cognitive impairment. Int Immunopharmacol 2024; 142:113146. [PMID: 39298819 DOI: 10.1016/j.intimp.2024.113146] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2024] [Revised: 08/12/2024] [Accepted: 09/08/2024] [Indexed: 09/22/2024]
Abstract
The cognitive decline associated with chronic metabolic disease diabetes has garnered extensive scrutiny, yet its pathogenesis remains incompletely understood, and the advancement of targeted therapeutics has posed a persistent challenge. Ferroptosis, a novel form of cell death characterized by intracellular lipid peroxidation and iron overload, has recently emerged as a significant factor. Numerous contemporary studies have corroborated that ferroptosis within the neurovascular unit is intimately associated with the onset of diabetes-induced cognitive impairment. Numerous contemporary studies have corroborated that ferroptosis within the neurovascular unit is intimately associated with the onset of diabetic cognitive impairment (DCI). This article initially conducts a profound analysis of the mechanism of ferroptosis, followed by a detailed elucidation of the specific manifestations of neurovascular unit ferroptosis in the context of diabetic cognitive function impairment. Furthermore, an exhaustive review of pertinent literature from April 2020 to March 2024 has been undertaken, resulting in the selection of 31 documents of significant reference value. These documents encompass studies on 11 distinct drugs, all of which are centered around investigating methods to inhibit the ferroptosis pathway as a potential treatment for DCI. Simultaneously, we conducted a review of 12 supplementary literary sources that presented 10 pharmacological agents with anti-ferroptosis properties in other neurodegenerative disorders. This article critically examines the potential influence of neurovascular unit ferroptosis on the progression of cognitive impairment in diabetes, from the three aforementioned perspectives, and organizes the existing and potential therapeutic drugs. It is our aspiration that this article will serve as a theoretical foundation for scholars in related disciplines when conceptualizing, investigating, and developing novel clinical drugs for DCI.
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Affiliation(s)
- Wenlan Zhang
- School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
| | - Yijing Yan
- School of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
| | - Chunmei Yi
- School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
| | - Xijuan Jiang
- School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
| | - Lin Guo
- School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
| | - Shanshan Huang
- School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
| | - Tong Xia
- School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
| | - Fayin Huang
- School of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
| | - Yike Jiao
- School of Acupuncture & Moxibustion and Tuina, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
| | - Huhu Li
- School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China.
| | - Bin Yu
- School of Medical Technology, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China.
| | - Yongna Dai
- School of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China.
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11
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Barone V, Surico PL, Cutrupi F, Mori T, Gallo Afflitto G, Di Zazzo A, Coassin M. The Role of Immune Cells and Signaling Pathways in Diabetic Eye Disease: A Comprehensive Review. Biomedicines 2024; 12:2346. [PMID: 39457658 PMCID: PMC11505591 DOI: 10.3390/biomedicines12102346] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2024] [Revised: 10/02/2024] [Accepted: 10/08/2024] [Indexed: 10/28/2024] Open
Abstract
Diabetic eye disease (DED) encompasses a range of ocular complications arising from diabetes mellitus, including diabetic retinopathy, diabetic macular edema, diabetic keratopathy, diabetic cataract, and glaucoma. These conditions are leading causes of visual impairments and blindness, especially among working-age adults. Despite advancements in our understanding of DED, its underlying pathophysiological mechanisms remain incompletely understood. Chronic hyperglycemia, oxidative stress, inflammation, and neurodegeneration play central roles in the development and progression of DED, with immune-mediated processes increasingly recognized as key contributors. This review provides a comprehensive examination of the complex interactions between immune cells, inflammatory mediators, and signaling pathways implicated in the pathogenesis of DED. By delving in current research, this review aims to identify potential therapeutic targets, suggesting directions of research for future studies to address the immunopathological aspects of DED.
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Affiliation(s)
- Vincenzo Barone
- Department of Ophthalmology, Campus Bio-Medico University, 00128 Rome, Italy; (V.B.); (F.C.); (T.M.); (A.D.Z.); (M.C.)
- Ophthalmology Operative Complex Unit, Campus Bio-Medico University Hospital Foundation, 00128 Rome, Italy
| | - Pier Luigi Surico
- Department of Ophthalmology, Campus Bio-Medico University, 00128 Rome, Italy; (V.B.); (F.C.); (T.M.); (A.D.Z.); (M.C.)
- Ophthalmology Operative Complex Unit, Campus Bio-Medico University Hospital Foundation, 00128 Rome, Italy
- Schepens Eye Research Institute of Massachusetts Eye and Ear, Harvard Medical School, Boston, MA 02114, USA
| | - Francesco Cutrupi
- Department of Ophthalmology, Campus Bio-Medico University, 00128 Rome, Italy; (V.B.); (F.C.); (T.M.); (A.D.Z.); (M.C.)
- Ophthalmology Operative Complex Unit, Campus Bio-Medico University Hospital Foundation, 00128 Rome, Italy
| | - Tommaso Mori
- Department of Ophthalmology, Campus Bio-Medico University, 00128 Rome, Italy; (V.B.); (F.C.); (T.M.); (A.D.Z.); (M.C.)
- Ophthalmology Operative Complex Unit, Campus Bio-Medico University Hospital Foundation, 00128 Rome, Italy
- Department of Ophthalmology, University of California San Diego, La Jolla, CA 92122, USA
| | - Gabriele Gallo Afflitto
- Ophthalmology Unit, Department of Experimental Medicine, University of Rome “Tor Vergata”, 00128 Rome, Italy;
- Moorfields Eye Hospital NHS Foundation Trust, London EC1V 2PD, UK
| | - Antonio Di Zazzo
- Department of Ophthalmology, Campus Bio-Medico University, 00128 Rome, Italy; (V.B.); (F.C.); (T.M.); (A.D.Z.); (M.C.)
- Ophthalmology Operative Complex Unit, Campus Bio-Medico University Hospital Foundation, 00128 Rome, Italy
| | - Marco Coassin
- Department of Ophthalmology, Campus Bio-Medico University, 00128 Rome, Italy; (V.B.); (F.C.); (T.M.); (A.D.Z.); (M.C.)
- Ophthalmology Operative Complex Unit, Campus Bio-Medico University Hospital Foundation, 00128 Rome, Italy
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12
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Moradi M, Hassanshahi J, Rahmani MR, Shamsizadeh A, Kaeidi A. Antiapoptotic and antinociceptive effects of Achillea millefolium L. aqueous extract in rats with experimental painful diabetic neuropathy. Res Pharm Sci 2024; 19:561-572. [PMID: 39691295 PMCID: PMC11648340 DOI: 10.4103/rps.rps_140_23] [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: 07/25/2023] [Revised: 11/24/2023] [Accepted: 09/11/2024] [Indexed: 12/19/2024] Open
Abstract
Background and purpose Neuropathy is one of the common complications of diabetes mellitus. This study aimed to determine the analgesic and antiapoptotic effects of the aqueous extract of Achillea millefolium L. (Ach) in rats with experimental painful diabetic neuropathy by behavioral and molecular procedures. Experimental approach Thirty male Wistar rats were divided into 5 groups including control, diabetes + saline, and diabetes + Ach extract (doses of 150, 300, and 600 mg/kg/day for 3 weeks, orally). A tail-flick test was performed to assess the pain threshold in different groups. Western blotting test was used to evaluate the apoptotic (Bax, Bcl2, cleaved caspase-3, and cytochrome-c) and inflammatory (TNF-α and NF-kB) protein factors in the lumbar portion of the spinal cord tissue. Also, commercial assay kits were used to evaluate oxidative stress factors (MDA, GPx, and SOD enzyme activity) in the lumbar portion of the spinal cord tissue. Findings/Results Results showed that administering Ach extract at the doses of 300 and 600 mg/kg/day significantly increased the nociception threshold in treated diabetic animals compared to untreated diabetic animals. Moreover, the treatment of diabetic animals with Ach extract (300 and 600 mg/kg/day) significantly reduced the oxidative stress, inflammation, and apoptosis biochemical indicators in the lumbar spinal cord tissue compared to the untreated diabetic group. Conclusion and implications The findings showed that Ach extract has neuroprotective and anti-nociceptive effects in rats with diabetic neuropathy. The effects can be due to the inhibition of oxidative stress, inflammation, and apoptosis in the spinal cord tissue.
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Affiliation(s)
- Mojtaba Moradi
- Physiology-Pharmacology Research Center, Research Institute of Basic Medical Sciences, Rafsanjan University of Medical Sciences, Rafsanjan, I.R. Iran
| | - Jalal Hassanshahi
- Department of Physiology and Pharmacology, School of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, I.R. Iran
| | - Mohammad Reza Rahmani
- Physiology-Pharmacology Research Center, Research Institute of Basic Medical Sciences, Rafsanjan University of Medical Sciences, Rafsanjan, I.R. Iran
| | - Ali Shamsizadeh
- Department of Physiology and Pharmacology, School of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, I.R. Iran
| | - Ayat Kaeidi
- Department of Physiology and Pharmacology, School of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, I.R. Iran
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13
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Summer M, Ali S, Fiaz U, Hussain T, Khan RRM, Fiaz H. Revealing the molecular mechanisms in wound healing and the effects of different physiological factors including diabetes, age, and stress. J Mol Histol 2024; 55:637-654. [PMID: 39120834 DOI: 10.1007/s10735-024-10223-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/29/2024] [Accepted: 07/05/2024] [Indexed: 08/10/2024]
Abstract
Wounds are the common fates in various microbial infections and physical damages including accidents, surgery, and burns. In response, a healthy body with a potent immune system heals that particular site within optimal time by following the coagulation, inflammation, proliferation, and remodeling phenomenon. However, certain malfunctions in the body due to various diseases particularly diabetes and other physiological factors like age, stress, etc., prolong the process of wound healing through various mechanisms including the Akt, Polyol, and Hexosamine pathways. The current review thoroughly explains the wound types, normal wound healing mechanisms, and the immune system's role. Moreover, the mechanistic role of diabetes is also elaborated comprehensively.
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Affiliation(s)
- Muhammad Summer
- Medical Toxicology and Biochemistry Laboratory, Department of Zoology, GC University Lahore, Lahore, 54000, Pakistan.
| | - Shaukat Ali
- Medical Toxicology and Biochemistry Laboratory, Department of Zoology, GC University Lahore, Lahore, 54000, Pakistan.
| | - Umaima Fiaz
- Medical Toxicology and Biochemistry Laboratory, Department of Zoology, GC University Lahore, Lahore, 54000, Pakistan
| | - Tauqeer Hussain
- Medical Toxicology and Biochemistry Laboratory, Department of Zoology, GC University Lahore, Lahore, 54000, Pakistan
| | | | - Hashim Fiaz
- Ammer-ud-Din Medical College, Lahore, 54000, Pakistan
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14
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Hajdú N, Rácz R, Tordai DZ, Békeffy M, Vági OE, Istenes I, Körei AE, Kempler P, Putz Z. Genetic Variants Influence the Development of Diabetic Neuropathy. Int J Mol Sci 2024; 25:6429. [PMID: 38928135 PMCID: PMC11203776 DOI: 10.3390/ijms25126429] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2024] [Revised: 05/22/2024] [Accepted: 06/06/2024] [Indexed: 06/28/2024] Open
Abstract
The exact mechanism by which diabetic neuropathy develops is still not fully known, despite our advances in medical knowledge. Progressing neuropathy may occur with a persistently favorable metabolic status in some patients with diabetes mellitus, while, in others, though seldom, a persistently unfavorable metabolic status is not associated with significant neuropathy. This might be significantly due to genetic differences. While recent years have brought compelling progress in the understanding of the pathogenetic background-in particular, accelerated progress is being made in understanding molecular biological mechanisms-some aspects are still not fully understood. A comparatively small amount of information is accessible on this matter; therefore, by summarizing the available data, in this review, we aim to provide a clearer picture of the current state of knowledge, identify gaps in the previous studies, and possibly suggest directions for future studies. This could help in developing more personalized approaches to the prevention and treatment of diabetic neuropathy, while also taking into account individual genetic profiles.
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15
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Bronowicka-Szydełko A, Gostomska-Pampuch K, Kuzan A, Pietkiewicz J, Krzystek-Korpacka M, Gamian A. Effect of advanced glycation end-products in a wide range of medical problems including COVID-19. Adv Med Sci 2024; 69:36-50. [PMID: 38335908 DOI: 10.1016/j.advms.2024.01.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2023] [Revised: 09/07/2023] [Accepted: 01/19/2024] [Indexed: 02/12/2024]
Abstract
Glycation is a physiological process that determines the aging of the organism, while in states of metabolic disorders it is significantly intensified. High concentrations of compounds such as reducing sugars or reactive aldehydes derived from lipid oxidation, occurring for example in diabetes, atherosclerosis, dyslipidemia, obesity or metabolic syndrome, lead to increased glycation of proteins, lipids and nucleic acids. The level of advanced glycation end-products (AGEs) in the body depends on rapidity of their production and the rate of their removal by the urinary system. AGEs, accumulated in the extracellular matrix of the blood vessels and other organs, cause irreversible changes in the biochemical and biomechanical properties of tissues. As a consequence, micro- and macroangiopathies appear in the system, and may contribute to the organ failure, like kidneys and heart. Elevated levels of AGEs also increase the risk of Alzheimer's disease and various cancers. In this paper, we propose a new classification due to modified amino acid residues: arginyl-AGEs, monolysyl-AGEs and lysyl-arginyl-AGEs and dilysyl-AGEs. Furthermore, we describe in detail the effect of AGEs on the pathogenesis of metabolic and old age diseases, such as diabetic complications, atherosclerosis and neurodegenerative diseases. We summarize the currently available data on the diagnostic value of AGEs and present the AGEs as a therapeutic goal in a wide range of medical problems, including SARS-CoV-2 infection and so-called long COVID.
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Affiliation(s)
| | | | - Aleksandra Kuzan
- Department of Medical Biochemistry, Wroclaw Medical University, Wroclaw, Poland.
| | - Jadwiga Pietkiewicz
- Department of Medical Biochemistry, Wroclaw Medical University, Wroclaw, Poland
| | | | - Andrzej Gamian
- Department of Immunology of Infectious Diseases, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland
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16
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Buonfiglio F, Wasielica-Poslednik J, Pfeiffer N, Gericke A. Diabetic Keratopathy: Redox Signaling Pathways and Therapeutic Prospects. Antioxidants (Basel) 2024; 13:120. [PMID: 38247544 PMCID: PMC10812573 DOI: 10.3390/antiox13010120] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2023] [Revised: 01/10/2024] [Accepted: 01/16/2024] [Indexed: 01/23/2024] Open
Abstract
Diabetes mellitus, the most prevalent endocrine disorder, not only impacts the retina but also significantly involves the ocular surface. Diabetes contributes to the development of dry eye disease and induces morphological and functional corneal alterations, particularly affecting nerves and epithelial cells. These changes manifest as epithelial defects, reduced sensitivity, and delayed wound healing, collectively encapsulated in the context of diabetic keratopathy. In advanced stages of this condition, the progression to corneal ulcers and scarring further unfolds, eventually leading to corneal opacities. This critical complication hampers vision and carries the potential for irreversible visual loss. The primary objective of this review article is to offer a comprehensive overview of the pathomechanisms underlying diabetic keratopathy. Emphasis is placed on exploring the redox molecular pathways responsible for the aberrant structural changes observed in the cornea and tear film during diabetes. Additionally, we provide insights into the latest experimental findings concerning potential treatments targeting oxidative stress. This endeavor aims to enhance our understanding of the intricate interplay between diabetes and ocular complications, offering valuable perspectives for future therapeutic interventions.
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Affiliation(s)
- Francesco Buonfiglio
- Department of Ophthalmology, University Medical Center, Johannes Gutenberg University Mainz, Langenbeckstrasse 1, 55131 Mainz, Germany; (J.W.-P.); (N.P.)
| | | | | | - Adrian Gericke
- Department of Ophthalmology, University Medical Center, Johannes Gutenberg University Mainz, Langenbeckstrasse 1, 55131 Mainz, Germany; (J.W.-P.); (N.P.)
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17
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Dwivedi J, Sachan P, Wal P, Wal A, Rai AK. Current State and Future Perspective of Diabetic Wound Healing Treatment: Present Evidence from Clinical Trials. Curr Diabetes Rev 2024; 20:e280823220405. [PMID: 37641999 DOI: 10.2174/1573399820666230828091708] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2022] [Revised: 03/29/2023] [Accepted: 05/01/2023] [Indexed: 08/31/2023]
Abstract
Diabetes is a chronic metabolic condition that is becoming more common and is characterised by sustained hyperglycaemia and long-term health effects. Diabetes-related wounds often heal slowly and are more susceptible to infection because of hyperglycaemia in the wound beds. The diabetic lesion becomes harder to heal after planktonic bacterial cells form biofilms. A potential approach is the creation of hydrogels with many functions. High priority is given to a variety of processes, such as antimicrobial, pro-angiogenesis, and general pro-healing. Diabetes problems include diabetic amputations or chronic wounds (DM). Chronic diabetes wounds that do not heal are often caused by low oxygen levels, increased reactive oxygen species, and impaired vascularization. Several types of hydrogels have been developed to get rid of contamination by pathogens; these hydrogels help to clean up the infection, reduce wound inflammation, and avoid necrosis. This review paper will focus on the most recent improvements and breakthroughs in antibacterial hydrogels for treating chronic wounds in people with diabetes. Prominent and significant side effects of diabetes mellitus include foot ulcers. Antioxidants, along with oxidative stress, are essential to promote the healing of diabetic wounds. Some of the problems that can come from a foot ulcer are neuropathic diabetes, ischemia, infection, inadequate glucose control, poor nutrition, also very high morbidity. Given the worrying rise in diabetes and, by extension, diabetic wounds, future treatments must focus on the rapid healing of diabetic wounds.
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Affiliation(s)
- Jyotsana Dwivedi
- Department of Pharmacy, PSIT-Pranveer Singh Institute of Technology, Kanpur, India
| | - Pranjal Sachan
- Department of Pharmacy, PSIT-Pranveer Singh Institute of Technology, Kanpur, India
| | - Pranay Wal
- Department of Pharmacy, PSIT-Pranveer Singh Institute of Technology, Kanpur, India
| | - Ankita Wal
- Department of Pharmacy, PSIT-Pranveer Singh Institute of Technology, Kanpur, India
| | - A K Rai
- Department of Pharmacy, PSIT-Pranveer Singh Institute of Technology, Kanpur, India
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18
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Miranda ER, Haus JM. Glyoxalase I is a novel target for the prevention of metabolic derangement. Pharmacol Ther 2023; 250:108524. [PMID: 37722607 DOI: 10.1016/j.pharmthera.2023.108524] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2023] [Revised: 08/07/2023] [Accepted: 08/29/2023] [Indexed: 09/20/2023]
Abstract
Obesity prevalence in the US has nearly tripled since 1975 and a parallel increase in prevalence of type 2 diabetes (T2D). Obesity promotes a myriad of metabolic derangements with insulin resistance (IR) being perhaps the most responsible for the development of T2D and other related diseases such as cardiovascular disease. The precarious nature of IR development is such that it provides a valuable target for the prevention of further disease development. However, the mechanisms driving IR are numerous and complex making the development of viable interventions difficult. The development of metabolic derangement in the context of obesity promotes accumulation of reactive metabolites such as the reactive alpha-dicarbonyl methylglyoxal (MG). MG accumulation has long been appreciated as a marker of disease progression in patients with T2D as well as the development of diabetic complications. However, recent evidence suggests that the accumulation of MG occurs with obesity prior to T2D onset and may be a primary driving factor for the development of IR and T2D. Further, emerging evidence also suggests that this accumulation of MG with obesity may be a result in a loss of MG detoxifying capacity of glyoxalase I. In this review, we will discuss the evidence that posits MG accumulation because of GLO1 attenuation is a novel target mechanism of the development of metabolic derangement. In addition, we will also explore the regulation of GLO1 and the strategies that have been investigated so far to target GLO1 regulation for the prevention and treatment of metabolic derangement.
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Affiliation(s)
- Edwin R Miranda
- School of Kinesiology, University of Michigan, Ann Arbor, MI, United States of America; Department of Nutrition and Integrative Physiology, University of Utah, Salt Lake City, UT, United States of America
| | - Jacob M Haus
- School of Kinesiology, University of Michigan, Ann Arbor, MI, United States of America.
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19
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Elzinga SE, Eid SA, McGregor BA, Jang DG, Hinder LM, Dauch JR, Hayes JM, Zhang H, Guo K, Pennathur S, Kretzler M, Brosius FC, Koubek EJ, Feldman EL, Hur J. Transcriptomic analysis of diabetic kidney disease and neuropathy in mouse models of type 1 and type 2 diabetes. Dis Model Mech 2023; 16:dmm050080. [PMID: 37791586 PMCID: PMC10565109 DOI: 10.1242/dmm.050080] [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: 01/13/2023] [Accepted: 04/26/2023] [Indexed: 10/05/2023] Open
Abstract
Diabetic kidney disease (DKD) and diabetic peripheral neuropathy (DPN) are common complications of type 1 (T1D) and type 2 (T2D) diabetes. However, the mechanisms underlying pathogenesis of these complications are unclear. In this study, we optimized a streptozotocin-induced db/+ murine model of T1D and compared it to our established db/db T2D mouse model of the same C57BLKS/J background. Glomeruli and sciatic nerve transcriptomic data from T1D and T2D mice were analyzed by self-organizing map and differential gene expression analysis. Consistent with prior literature, pathways related to immune function and inflammation were dysregulated in both complications in T1D and T2D mice. Gene-level analysis identified a high degree of concordance in shared differentially expressed genes (DEGs) in both complications and across diabetes type when using mice from the same cohort and genetic background. As we have previously shown a low concordance of shared DEGs in DPN when using mice from different cohorts and genetic backgrounds, this suggests that genetic background may influence diabetic complications. Collectively, these findings support the role of inflammation and indicate that genetic background is important in complications of both T1D and T2D.
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Affiliation(s)
- Sarah E. Elzinga
- Department of Neurology, University of Michigan, Ann Arbor, MI 48109, USA
| | - Stephanie A. Eid
- Department of Neurology, University of Michigan, Ann Arbor, MI 48109, USA
| | - Brett A. McGregor
- Department of Biomedical Sciences, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND 58202, USA
| | - Dae-Gyu Jang
- Department of Neurology, University of Michigan, Ann Arbor, MI 48109, USA
| | - Lucy M. Hinder
- Department of Neurology, University of Michigan, Ann Arbor, MI 48109, USA
| | | | - John M. Hayes
- Department of Neurology, University of Michigan, Ann Arbor, MI 48109, USA
| | - Hongyu Zhang
- Division of Nephrology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA
| | - Kai Guo
- Department of Neurology, University of Michigan, Ann Arbor, MI 48109, USA
| | - Subramaniam Pennathur
- Division of Nephrology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA
- Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI 48109, USA
| | - Matthias Kretzler
- Division of Nephrology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA
- Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA
| | - Frank C. Brosius
- Division of Nephrology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA
- Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI 48109, USA
- Department of Medicine, University of Arizona, Tucson, AZ 85721, USA
| | - Emily J. Koubek
- Department of Neurology, University of Michigan, Ann Arbor, MI 48109, USA
| | - Eva L. Feldman
- Department of Neurology, University of Michigan, Ann Arbor, MI 48109, USA
| | - Junguk Hur
- Department of Biomedical Sciences, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND 58202, USA
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20
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Wang S, Qin S, Cai B, Zhan J, Chen Q. Promising therapeutic mechanism for Chinese herbal medicine in ameliorating renal fibrosis in diabetic nephropathy. Front Endocrinol (Lausanne) 2023; 14:932649. [PMID: 37522131 PMCID: PMC10376707 DOI: 10.3389/fendo.2023.932649] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2022] [Accepted: 06/22/2023] [Indexed: 08/01/2023] Open
Abstract
Diabetic nephropathy (DN) is one of the most serious chronic microvascular abnormalities of diabetes mellitus and the major cause of uremia. Accumulating evidence has confirmed that fibrosis is a significant pathological feature that contributes to the development of chronic kidney disease in DN. However, the exact mechanism of renal fibrosis in DN is still unclear, which greatly hinders the treatment of DN. Chinese herbal medicine (CHM) has shown efficacy and safety in ameliorating inflammation and albuminuria in diabetic patients. In this review, we outline the underlying mechanisms of renal fibrosis in DN, including oxidative stress (OS) generation and OS-elicited ASK1-p38/JNK activation. Also, we briefly summarize the current status of CHM treating DN by improving renal fibrosis. The treatment of DN by inhibiting ASK1 activation to alleviate renal fibrosis in DN with CHM will promote the discovery of novel therapeutic targets for DN and provide a beneficial therapeutic method for DN.
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Affiliation(s)
- Shengju Wang
- Department of Nephrology, The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou, China
- Department of Endocrinology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
| | - Shuai Qin
- Department of Nephrology, The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou, China
| | - Baochao Cai
- Diabetes Department, Jiaxing Hospital of Traditional Chinese Medicine, Jiaxing, Zhejiang, China
| | - Jihong Zhan
- Department of Nephrology, The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou, China
| | - Qiu Chen
- Department of Endocrinology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
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21
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Lin Q, Li K, Chen Y, Xie J, Wu C, Cui C, Deng B. Oxidative Stress in Diabetic Peripheral Neuropathy: Pathway and Mechanism-Based Treatment. Mol Neurobiol 2023:10.1007/s12035-023-03342-7. [PMID: 37115404 DOI: 10.1007/s12035-023-03342-7] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2022] [Accepted: 04/04/2023] [Indexed: 04/29/2023]
Abstract
Diabetic peripheral neuropathy (DPN) is a major complication of diabetes mellitus with a high incidence. Oxidative stress, which is a crucial pathophysiological pathway of DPN, has attracted much attention. The distortion in the redox balance due to the overproduction of reactive oxygen species (ROS) and the deregulation of antioxidant defense systems promotes oxidative damage in DPN. Therefore, we have focused on the role of oxidative stress in the pathogenesis of DPN and elucidated its interaction with other physiological pathways, such as the glycolytic pathway, polyol pathway, advanced glycosylation end products, protein kinase C pathway, inflammation, and non-coding RNAs. These interactions provide novel therapeutic options targeting oxidative stress for DPN. Furthermore, our review addresses the latest therapeutic strategies targeting oxidative stress for the rehabilitation of DPN. Antioxidant supplements and exercise have been proposed as fundamental therapeutic strategies for diabetic patients through ROS-mediated mechanisms. In addition, several novel drug delivery systems can improve the bioavailability of antioxidants and the efficacy of DPN.
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Affiliation(s)
- Qingxia Lin
- Department of Psychiatry, First Affiliated Hospital of Wenzhou Medical University, Wenzhou Medical University, Wenzhou, People's Republic of China
| | - Kezheng Li
- Department of Neurology, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People's Republic of China
- First School of Clinical Medicine, Wenzhou Medical University, Wenzhou, People's Republic of China
| | - Yinuo Chen
- Department of Neurology, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People's Republic of China
- First School of Clinical Medicine, Wenzhou Medical University, Wenzhou, People's Republic of China
| | - Jiali Xie
- Department of Neurology, Shanghai East Hospital, Tongji University, Shanghai, People's Republic of China
| | - Chunxue Wu
- Department of Neurology, Wencheng County People's Hospital, Wenzhou, People's Republic of China
| | - Can Cui
- Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Binbin Deng
- Department of Neurology, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People's Republic of China.
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22
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Karami F, Jamaati H, Coleman-Fuller N, Zeini MS, Hayes AW, Gholami M, Salehirad M, Darabi M, Motaghinejad M. Is metformin neuroprotective against diabetes mellitus-induced neurodegeneration? An updated graphical review of molecular basis. Pharmacol Rep 2023; 75:511-543. [PMID: 37093496 DOI: 10.1007/s43440-023-00469-1] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2022] [Revised: 02/21/2023] [Accepted: 02/23/2023] [Indexed: 04/25/2023]
Abstract
Diabetes mellitus (DM) is a metabolic disease that activates several molecular pathways involved in neurodegenerative disorders. Metformin, an anti-hyperglycemic drug used for treating DM, has the potential to exert a significant neuroprotective role against the detrimental effects of DM. This review discusses recent clinical and laboratory studies investigating the neuroprotective properties of metformin against DM-induced neurodegeneration and the roles of various molecular pathways, including mitochondrial dysfunction, oxidative stress, inflammation, apoptosis, and its related cascades. A literature search was conducted from January 2000 to December 2022 using multiple databases including Web of Science, Wiley, Springer, PubMed, Elsevier Science Direct, Google Scholar, the Core Collection, Scopus, and the Cochrane Library to collect and evaluate peer-reviewed literature regarding the neuroprotective role of metformin against DM-induced neurodegenerative events. The literature search supports the conclusion that metformin is neuroprotective against DM-induced neuronal cell degeneration in both peripheral and central nervous systems, and this effect is likely mediated via modulation of oxidative stress, inflammation, and cell death pathways.
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Affiliation(s)
- Fatemeh Karami
- Chronic Respiratory Disease Research Center (CRDRC), National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hamidreza Jamaati
- Chronic Respiratory Disease Research Center (CRDRC), National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Natalie Coleman-Fuller
- Department of Veterinary and Biomedical Sciences, University of Minnesota, Saint Paul, MN, 55108, USA
| | - Maryam Shokrian Zeini
- Chronic Respiratory Disease Research Center (CRDRC), National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - A Wallace Hayes
- University of South Florida College of Public Health and Institute for Integrative Toxicology, Michigan State University, East Lansing, USA
| | - Mina Gholami
- Chronic Respiratory Disease Research Center (CRDRC), National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mahsa Salehirad
- Cognitive and Neuroscience Research Center (CNRC), Amir-Almomenin Hospital, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Mohammad Darabi
- Chronic Respiratory Disease Research Center (CRDRC), National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Majid Motaghinejad
- Chronic Respiratory Disease Research Center (CRDRC), National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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23
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Dah-Nouvlessounon D, Chokki M, Noumavo ADP, Cârâc G, Furdui B, Sina H, Zongo C, Savadogo A, Baba-Moussa L, Dinica RM, Baba-Moussa F. Ethnopharmacological Value and Biological Activities via Antioxidant and Anti-Protein Denaturation Activity of Morinda lucida Benth and Momordica charantia L. Leaves Extracts from Benin. PLANTS (BASEL, SWITZERLAND) 2023; 12:1228. [PMID: 36986917 PMCID: PMC10058355 DOI: 10.3390/plants12061228] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 02/05/2023] [Revised: 02/25/2023] [Accepted: 03/06/2023] [Indexed: 06/18/2023]
Abstract
Momordica charantia Linn. (Cucurbitaceae), the wild variety of bitter melon, and Morinda lucida Benth (Rubiaceae) were commonly used as a popular folk medicine in Benin. This study aimed to appreciate the ethnopharmacological knowledge and evaluate the antioxidant and anti-inflammatory effects of M. charantia and M. lucida leaves extracts. Semi-structured surveys supported by individual interviews were conducted with herbalists and traditional healers in southern Benin. The antioxidant activities were evaluated by a micro-dilution technique using ABTS and FRAP methods. These activities were supported by cyclic voltammetry analysis. The anti-inflammatory activity was evaluated by the albumin denaturation method. The volatile compounds were analysed by GC-MS analysis. All the respondents involved in this study have good knowledge of the two plants. We identify 21 diseases grouped into five categories of condition. The two plants' extracts possess variable antioxidant capacity. Indeed, all the active extracts of M. charantia presented an IC50 < 0.078 mg/mL, while the extracts of M. lucida had an IC50 up to 0.21 ± 0.02 mg/mL. For anti-inflammatory activity, a dose-response activity (p < 0.001) was observed in the protein denaturation inhibition rate of the extracts. It should be noted that the highest inhibition rate (98.34 ± 0.12) of the albumin denaturation was observed with M. lucida dichloromethane extract. A total of 59 volatile compounds were identified by GC-MS analysis in the extracts of the two plants. The M. charantia ethyl acetate extract shows the presence of 30 different compounds with a relative abundance of 98.83%, while that of M. lucida shows 24 compounds with a relative abundance of 98.30%. These plants are potential candidates to discover new compounds with therapeutic properties that could be used to solve public health problems.
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Affiliation(s)
- Durand Dah-Nouvlessounon
- Laboratory of Biology and Molecular Typing in Microbiology, Department of Biochemistry and Cell Biology, Faculty of Sciences and Technic, University of Abomey-Calavi, Cotonou 05BP1604, Benin; (D.D.-N.); (A.D.P.N.)
- Department of Chemistry, Physics and Environment, “Dunarea de Jos” University of Galati, Domneasca Street 47, 800008 Galati, Romania; (M.C.); (G.C.)
| | - Michaelle Chokki
- Department of Chemistry, Physics and Environment, “Dunarea de Jos” University of Galati, Domneasca Street 47, 800008 Galati, Romania; (M.C.); (G.C.)
- Laboratoire de Microbiologie et de Technologie Alimentaire, FAST, Département de Biologie Végétale, Université d’Abomey-Calavi, ISBA-Champ de Foire, Cotonou 01BP: 526, Benin
- Centre de Recherche en Sciences Biologiques, Alimentaires et Nutritionnelles (CRSBAN), UFR-SVT, Université de Ougadougou, Ougadougou 03BP7131, Burkina Faso
| | - Agossou Damien Pacôme Noumavo
- Laboratory of Biology and Molecular Typing in Microbiology, Department of Biochemistry and Cell Biology, Faculty of Sciences and Technic, University of Abomey-Calavi, Cotonou 05BP1604, Benin; (D.D.-N.); (A.D.P.N.)
- Laboratoire de Microbiologie et de Technologie Alimentaire, FAST, Département de Biologie Végétale, Université d’Abomey-Calavi, ISBA-Champ de Foire, Cotonou 01BP: 526, Benin
| | - Geta Cârâc
- Department of Chemistry, Physics and Environment, “Dunarea de Jos” University of Galati, Domneasca Street 47, 800008 Galati, Romania; (M.C.); (G.C.)
| | - Bianca Furdui
- Department of Chemistry, Physics and Environment, “Dunarea de Jos” University of Galati, Domneasca Street 47, 800008 Galati, Romania; (M.C.); (G.C.)
| | - Haziz Sina
- Laboratory of Biology and Molecular Typing in Microbiology, Department of Biochemistry and Cell Biology, Faculty of Sciences and Technic, University of Abomey-Calavi, Cotonou 05BP1604, Benin; (D.D.-N.); (A.D.P.N.)
| | - Cheikna Zongo
- Centre de Recherche en Sciences Biologiques, Alimentaires et Nutritionnelles (CRSBAN), UFR-SVT, Université de Ougadougou, Ougadougou 03BP7131, Burkina Faso
| | - Aly Savadogo
- Centre de Recherche en Sciences Biologiques, Alimentaires et Nutritionnelles (CRSBAN), UFR-SVT, Université de Ougadougou, Ougadougou 03BP7131, Burkina Faso
| | - Lamine Baba-Moussa
- Laboratory of Biology and Molecular Typing in Microbiology, Department of Biochemistry and Cell Biology, Faculty of Sciences and Technic, University of Abomey-Calavi, Cotonou 05BP1604, Benin; (D.D.-N.); (A.D.P.N.)
| | - Rodica-Mihaela Dinica
- Department of Chemistry, Physics and Environment, “Dunarea de Jos” University of Galati, Domneasca Street 47, 800008 Galati, Romania; (M.C.); (G.C.)
| | - Farid Baba-Moussa
- Laboratoire de Microbiologie et de Technologie Alimentaire, FAST, Département de Biologie Végétale, Université d’Abomey-Calavi, ISBA-Champ de Foire, Cotonou 01BP: 526, Benin
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Lindholm E, Ekman L, Elgzyri T, Lindholm B, Löndahl M, Dahlin L. Diabetic Neuropathy Assessed with Multifrequency Vibrometry Develops Earlier than Nephropathy but Later than Retinopathy. Exp Clin Endocrinol Diabetes 2023; 131:187-193. [PMID: 36626938 DOI: 10.1055/a-2010-6987] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
BACKGROUND Diabetes is associated with systemic complications. Prevalence of diabetic nephropathy, and retinopathy, in type 1 diabetes mellitus (T1DM) is declining, but it is not known if this is true also for diabetic neuropathy. AIM To investigate the relationship between large fibre diabetic neuropathy and other diabetic complications. MATERIALS AND METHODS Neuropathy, defined here as large fibre neuropathy, was assessed by measuring vibration perception thresholds at four different frequencies on the sole of the foot, using a standard VibroSense Meter and/or neuropathic symptoms, in 599 individuals with T1DM. Retinopathy status was graded using the International Clinical Disease Severity Scale. Grade of albuminuria and previous history of any macrovascular complications were registered. RESULTS Diabetic individuals without retinopathy had similar vibration thresholds as age- and gender-matched control participants without diabetes, whereas those without microalbuminuria had higher thresholds than controls. Two individuals out of 599 (0.3%) had microalbuminuria, but not retinopathy or neuropathy, and 12/134 (9%) without retinopathy had signs of neuropathy. Totally 119/536 (22%) of the patients without microalbuminuria had neuropathy. Vibration thresholds increased with the rising severity of retinopathy and grade of albuminuria. In a multinomial logistic regression analysis, neuropathy was associated with retinopathy (OR 2.96 [1.35-6.49], p=0.007), nephropathy (OR 6.25 [3.21-12.15]; p=6.7×10-8) and macrovascular disease (OR 2.72 [1.50-4.93], p=0.001). CONCLUSIONS Despite recent changes in the incidence of diabetic complications, the onset of large fibre neuropathy follows that of retinopathy but precedes the onset of nephropathy in T1DM.
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Affiliation(s)
- Eero Lindholm
- Department of Clinical Sciences, Endocrinology, Lund University, Malmö, Sweden
| | - Linnea Ekman
- Department of Translational Medicine - Hand Surgery, Lund University, Malmö, Sweden
| | - Targ Elgzyri
- Department of Clinical Sciences, Endocrinology, Lund University, Malmö, Sweden
| | - Beata Lindholm
- Department of Clinical Sciences, Neurology, Lund University, Malmö, Sweden
| | - Magnus Löndahl
- Department of Clinical Sciences, Endocrinology, Lund University, Lund, Sweden
| | - Lars Dahlin
- Department of Translational Medicine - Hand Surgery, Lund University, Malmö, Sweden.,Department of Hand Surgery, Skåne University Hospital, Malmö, Sweden
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Wang X, Xu G, Liu H, Chen Z, Huang S, Yuan J, Xie C, Du L. Inhibiting apoptosis of Schwann cell under the high-glucose condition: A promising approach to treat diabetic peripheral neuropathy using Chinese herbal medicine. Biomed Pharmacother 2023; 157:114059. [PMID: 36462309 DOI: 10.1016/j.biopha.2022.114059] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2022] [Revised: 11/15/2022] [Accepted: 11/27/2022] [Indexed: 12/05/2022] Open
Abstract
Diabetic peripheral neuropathy (DPN) is a common complication of diabetes. Glycemic control and lifestyle alterations cannot prevent the development of DPN; therefore, investigating effective treatments for DPN is crucial. Schwann cells (SCs) maintain the physiological function of peripheral nerves and promote the repair and regeneration of injured nerves. Inhibiting the apoptosis of SCs through various pathological pathways in a high-glucose environment plays an important role in developing DPN. Therefore, inhibiting the apoptosis of SCs can be a novel treatment strategy for DPN. Previous studies have indicated the potential of Chinese herbal medicine (CHM) in treating DPN. In this study, we have reviewed the effects of CHM (both monomers and extracts) on the apoptosis of SCs by interfering with the production of advanced glycation end products, oxidative stress, and endoplasmic reticulum stress pathological pathways. This review will demonstrate the potentialities of CHM in inhibiting apoptosis in SCs, providing new insights and perspectives for treating DPN.
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Affiliation(s)
- Xueru Wang
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu610072, Sichuan, China; TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Chengdu, 610072, Sichuan, China.
| | - Gang Xu
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu610072, Sichuan, China; TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Chengdu, 610072, Sichuan, China.
| | - Hanyu Liu
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu610072, Sichuan, China.
| | - Zhengtao Chen
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu610072, Sichuan, China.
| | - Susu Huang
- College of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, Sichuan, China.
| | - Jiushu Yuan
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu610072, Sichuan, China.
| | - Chunguang Xie
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu610072, Sichuan, China; TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Chengdu, 610072, Sichuan, China.
| | - Lian Du
- College of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, Sichuan, China.
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26
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Toprak V, Akalın SA, Öcal E, Çavuş Y, Özdemir İ. Histopathological examination of the protective effect of intense exercise in apoptotic germ cell damage due to diabetes. Acta Cir Bras 2023; 38:e381423. [PMID: 37098926 PMCID: PMC10129294 DOI: 10.1590/acb381423] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2023] [Accepted: 02/22/2023] [Indexed: 04/27/2023] Open
Abstract
PURPOSE The aim of this study was to determine the protective and antioxidative effects of intensive exercise on streptozotocin (STZ)-induced testicular damage, apoptotic spermatognial cells death, and oxidative stress. METHODS 36 male Sprague Dawley rats were divided into three groups: control, diabetes, and diabetes+intensive exercise (IE) groups. Testicular tissues were examined histopathologically and antioxidant enzymes, including catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and malondialdehyde (MDA) activity, as well as serum testosterone level, were measured. RESULTS Seminiferous tubules and germ cells were found to be better in the testis tissue of the intense exercise group than in the diabetes group. Diabetes suppressed antioxidant enzymes CAT, SOD, GPx and testosterone levels were significantly decreased, and increased MDA level in the diabetic group compared to diabetes+IE group (p < 0.001). Following four weeks of treatment, intensive exercise improved the antioxidant defense, significantly decreased MDA activity, and increased testosterone levels in testicular tissue in the diabetic group compared to diabetes+IE group (p < 0.01). CONCLUSIONS STZ-induced diabetes causes damage to the testis tissue. In order to prevent these damages, exercise practice has become very popular nowadays. In present study, our intensive exercise protocol, histological, and biochemical analysis of the effect of diabetes on the testicular tissues is shown.
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Affiliation(s)
- Veysel Toprak
- Eyyübiye Education and Research Hospital - Department of Gynecology and Obstetrics - Şanlıurfa, Turkey
| | - Senem Alkan Akalın
- Private Medical Practice - Department of Gynecology and Obstetrics - Diyarbakir, Turkey
| | - Ece Öcal
- Antalya Research and Education Hospital - Department of Perinatology - Antalya, Turkey
| | - Yunus Çavuş
- Diyarbakir Memorial Hospital - Department of Gynecology and Obstetrics - Diyarbakir, Turkey
| | - İlhan Özdemir
- Atatürk University - Faculty of Medicine - Department of Gynecology and Obstetrics - Erzurum, Turkey
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Fortingo N, Melnyk S, Sutton SH, Watsky MA, Bollag WB. Innate Immune System Activation, Inflammation and Corneal Wound Healing. Int J Mol Sci 2022; 23:14933. [PMID: 36499260 PMCID: PMC9740891 DOI: 10.3390/ijms232314933] [Citation(s) in RCA: 36] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2022] [Revised: 11/09/2022] [Accepted: 11/14/2022] [Indexed: 12/05/2022] Open
Abstract
Corneal wounds resulting from injury, surgeries, or other intrusions not only cause pain, but also can predispose an individual to infection. While some inflammation may be beneficial to protect against microbial infection of wounds, the inflammatory process, if excessive, may delay corneal wound healing. An examination of the literature on the effect of inflammation on corneal wound healing suggests that manipulations that result in reductions in severe or chronic inflammation lead to better outcomes in terms of corneal clarity, thickness, and healing. However, some acute inflammation is necessary to allow efficient bacterial and fungal clearance and prevent corneal infection. This inflammation can be triggered by microbial components that activate the innate immune system through toll-like receptor (TLR) pathways. In particular, TLR2 and TLR4 activation leads to pro-inflammatory nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) activation. Similarly, endogenous molecules released from disrupted cells, known as damage-associated molecular patterns (DAMPs), can also activate TLR2, TLR4 and NFκB, with the resultant inflammation worsening the outcome of corneal wound healing. In sterile keratitis without infection, inflammation can occur though TLRs to impact corneal wound healing and reduce corneal transparency. This review demonstrates the need for acute inflammation to prevent pathogenic infiltration, while supporting the idea that a reduction in chronic and/or excessive inflammation will allow for improved wound healing.
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Affiliation(s)
- Nyemkuna Fortingo
- Department of Physiology, Medical College of Georgia, Augusta University, Augusta, GA 30907, USA
| | - Samuel Melnyk
- Department of Physiology, Medical College of Georgia, Augusta University, Augusta, GA 30907, USA
- James and Jean Culver Vision Discovery Institute, Medical College of Georgia, Augusta University, Augusta, GA 30907, USA
| | - Sarah H. Sutton
- Department of Medical Illustration, Augusta University, Augusta, GA 30907, USA
| | - Mitchell A. Watsky
- James and Jean Culver Vision Discovery Institute, Medical College of Georgia, Augusta University, Augusta, GA 30907, USA
- Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, GA 30907, USA
| | - Wendy B. Bollag
- Department of Physiology, Medical College of Georgia, Augusta University, Augusta, GA 30907, USA
- James and Jean Culver Vision Discovery Institute, Medical College of Georgia, Augusta University, Augusta, GA 30907, USA
- Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, GA 30907, USA
- Charlie Norwood VA Medical Center, Augusta, GA 30904, USA
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Albalawi MA, Abdelaziz AM, Attia MS, Saied E, Elganzory HH, Hashem AH. Mycosynthesis of Silica Nanoparticles Using Aspergillus niger: Control of Alternaria solani Causing Early Blight Disease, Induction of Innate Immunity and Reducing of Oxidative Stress in Eggplant. Antioxidants (Basel) 2022; 11:2323. [PMID: 36552531 PMCID: PMC9774718 DOI: 10.3390/antiox11122323] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2022] [Revised: 11/13/2022] [Accepted: 11/16/2022] [Indexed: 11/25/2022] Open
Abstract
The threats to the life and production of crops are exacerbated by climate change and the misuse of chemical pesticides. This study was designed to evaluate the effectiveness of biosynthesized silica nanoparticles (SiO2-NPs) as an alternative to pesticides against early blight disease of eggplant. Antifungal activity, disease index, photosynthetic pigments, osmolytes, oxidative stress, antioxidant enzymes activities were tested for potential tolerance of eggplant infected with Alternaria solani. Silica nanoparticles were successfully biosynthesized using Aspergillus niger through green and ecofriendly method. Results revealed that SiO2-NPs exhibited promising antifungal activity against A. solani where MIC was 62.5 µg/mL, and inhibition growth at concentration 1000 µg/mL recorded 87.8%. The disease Index (DI) as a result of infection with A. solani reached 82.5%, and as a result, a severe decrease in stem and root length and number of leaves occurred, which led to a sharp decrease in the photosynthetic pigments. However, contents of free proline, total phenol and antioxidant enzymes activity were increased in infected plants. On the other hand, the treatment with SiO2-NPs 100 ppm led to a great reduction in the disease Index (DI) by 25% and a high protection rate by 69.69%. A clear improvement in growth characteristics and a high content of chlorophyll and total carotenoids was also observed in the plants as a result of treatment with silica nanoparticles in (healthy and infected) plants. Interestingly, the noticeable rise in the content of infected and healthy plants of proline and phenols and an increase in the activity of super oxide dismutase (SOD) and polyphenol oxidase (PPO). It could be suggested that foliar application of SiO2-NPs especially 100 ppm could be commercially used as antifungal and strong inducer of plant physiological immunity against early blight disease.
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Affiliation(s)
- Marzough A. Albalawi
- Department of Chemistry, Alwajh College, University of Tabuk, Tabuk 71491, Saudi Arabia
| | - Amer M. Abdelaziz
- Botany and Microbiology Department, Faculty of Science, Al-Azhar University, Nasr City, Cairo 11884, Egypt
| | - Mohamed S. Attia
- Botany and Microbiology Department, Faculty of Science, Al-Azhar University, Nasr City, Cairo 11884, Egypt
| | - Ebrahim Saied
- Botany and Microbiology Department, Faculty of Science, Al-Azhar University, Nasr City, Cairo 11884, Egypt
| | - Hussein H. Elganzory
- Department of Chemistry, College of Science, Qassim University, Buraidah 51452, Saudi Arabia
| | - Amr H. Hashem
- Botany and Microbiology Department, Faculty of Science, Al-Azhar University, Nasr City, Cairo 11884, Egypt
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Kiyat P, Kose T, Gümüstas B, Selver OB. Evaluation of Corneal Sensitivity and Quadrature Variability in Patients with Diabetic Neuropathy. Middle East Afr J Ophthalmol 2022; 29:200-204. [PMID: 38162562 PMCID: PMC10754107 DOI: 10.4103/meajo.meajo_111_23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2023] [Revised: 09/07/2023] [Accepted: 09/13/2023] [Indexed: 01/03/2024] Open
Abstract
PURPOSE The purpose of the study was to evaluate the corneal sensitivity and its quadrature variability in patients with diabetic neuropathy (DN) diagnosed with electromyography and to compare these results with age- and sex-matched healthy individuals. METHODS The left eyes of 32 patients who applied for refraction or fundus examination and had a diagnosis of DN by electromyography in their medical history were included in this study. Corneal sensitivity was evaluated using the Cochet-Bonnet esthesiometer (Luneau, Paris) in five zones: central, nasal, superior, temporal, and inferior. The measurements of the patients were compared with the measurements of 32 age- and sex-matched healthy volunteers. Furthermore, the measurements of five corneal zones were compared with each other, and the level of correlation was investigated in each group. RESULTS The central corneal sensitivity values were measured as 4.12 ± 1.04 (mm) and 5.92 ± 0.14 (mm) (P < 0.001). While the sensitivity values at the superior, inferior, nasal, and temporal quadrants were detected as 5.85 ± 0.21, 5.85 ± 0.26, 5.94 ± 0.13, 5.93 ± 0.13, and 5.92 ± 0.14 (mm) in the control group, it was measured as 3.67 ± 0.66, 3.67 ± 0.62, 3.67 ± 0.62, and 3.89 ± 0.73 (mm) in the DN group, respectively. The corneal sensitivity values were all found to be significantly lower in the DN group (P < 0.001 for all parameters) at all quadrants as well as the central cornea. Furthermore, a moderate positive correlation between all five zones in the control group and a very strong positive correlation in the DN group were found in terms of the corneal quadrature sensitivity. CONCLUSION The current study revealed a significant reduction in corneal sensitivity in patients with DN. In both the control group and DN group, all corneal zones showed positive correlations which show the consistency of the measurement in different quadratures. Evaluating corneal sensitivity with a Cochet-Bonnet esthesiometer might serve as a useful screening tool in detecting neuropathy development. By taking the necessary precautions, further damage can be prevented.
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Affiliation(s)
- Pelin Kiyat
- Department of Ophthalmology, Buca Seyfi Demirsoy Training and Research Hospital, Izmir Democracy University, Izmir, Turkey
| | - Timur Kose
- Department of Biostatistics and Medical Informatics, Ege University, Izmir, Turkey
| | - Banu Gümüstas
- Department of Neurology, Buca Seyfi Demirsoy Training and Research Hospital, Izmir, Turkey
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Gimenes GM, Santana GO, Scervino MVM, Curi R, Pereira JNB. A short review on the features of the non-obese diabetic Goto-Kakizaki rat intestine. Braz J Med Biol Res 2022; 55:e11910. [PMID: 36000611 PMCID: PMC9394691 DOI: 10.1590/1414-431x2022e11910] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2021] [Accepted: 06/30/2022] [Indexed: 11/23/2022] Open
Abstract
The Goto-Kakizaki (GK) rat is a non-obese experimental model of type 2 diabetes
mellitus (T2DM) that allows researchers to monitor diabetes-induced changes
without jeopardizing the effects of obesity. This rat strain exhibits notable
gastrointestinal features associated with T2DM, such as marked alterations in
intestinal morphology, reduced intestinal motility, slow transit, and modified
microbiota compared to Wistar rats. The primary treatments for diabetic patients
include administration of hypoglycemic agents and insulin, and lifestyle
changes. Emerging procedures, including alternative therapies, metabolic
surgeries, and modulation of the intestinal microbiota composition, have been
shown to improve the diabetic state of GK rats. This review describes the
morpho-physiological diabetic-associated features of the gastrointestinal tract
(GIT) of GK rats. We also describe promising strategies, e.g., metabolic surgery
and modulation of gut microbiota composition, used to target the GIT of this
animal model to improve the diabetic state.
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Affiliation(s)
- G M Gimenes
- Programa de Pós-Graduação Interdisciplinar em Ciências da Saúde, Universidade Cruzeiro do Sul, São Paulo, SP, Brasil
| | - G O Santana
- Programa de Pós-Graduação Interdisciplinar em Ciências da Saúde, Universidade Cruzeiro do Sul, São Paulo, SP, Brasil
| | - M V M Scervino
- Programa de Pós-Graduação Interdisciplinar em Ciências da Saúde, Universidade Cruzeiro do Sul, São Paulo, SP, Brasil
| | - R Curi
- Programa de Pós-Graduação Interdisciplinar em Ciências da Saúde, Universidade Cruzeiro do Sul, São Paulo, SP, Brasil.,Centro Bioindustrial, Instituto Butantan, São Paulo, SP, Brasil
| | - J N B Pereira
- Laboratório Estratégico de Diagnóstico Molecular, Instituto Butantan, São Paulo, SP, Brasil
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Zainal Z, Khaza'ai H, Kutty Radhakrishnan A, Chang SK. Therapeutic potential of palm oil vitamin E-derived tocotrienols in inflammation and chronic diseases: Evidence from preclinical and clinical studies. Food Res Int 2022; 156:111175. [DOI: 10.1016/j.foodres.2022.111175] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2021] [Revised: 03/17/2022] [Accepted: 03/17/2022] [Indexed: 12/17/2022]
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Abicca I, Giannini D, Gilardi M, Roszkowska AM, Parravano M, Picconi F, Frontoni S, Schiano-Lomoriello D. A Novel Algorithm for the Evaluation of Corneal Nerve Beadings by in vivo Confocal Microscopy in Patients With Type 1 Diabetes Mellitus. Front Med (Lausanne) 2022; 9:897259. [PMID: 35646958 PMCID: PMC9133533 DOI: 10.3389/fmed.2022.897259] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2022] [Accepted: 04/13/2022] [Indexed: 11/23/2022] Open
Abstract
Purpose Peripheral neuropathy could complicate diabetes mellitus (DM). In vivo confocal microscopy (IVCM) is an ocular examination for the diagnosis of small fiber neuropathies and the detection of the earliest corneal sub-basal nerve plexus (SBP) alterations. Corneal SBP characteristics include focal enlargement along with the nerve fiber, called corneal beadings. These dilatations represent a mitochondrial accumulation induced by the reactive oxygen stress, as a consequence of hyperglycemia. For this reason, corneal beadings are considered indicative of metabolic activity. This study aimed to describe the corneal characteristics of a population of type 1 diabetes mellitus (T1DM) well metabolically controlled, using a new algorithm for the analysis of corneal beading size (BS). Methods Patients aged ≥18 years affected by T1DM were compared with healthy subjects who underwent IVCM (Confoscan 4; Nidek Technologies Padova, Italy). Starting from the coordinates of the beadings detected by the IVCM, we implemented a new algorithm for automatically measuring BS in corneal SBP images. Results We compared 20 eyes of T1DM patients with 26 healthy controls. The corneal nerves' fiber length (p = 0.008), corneal nerves' fiber length density (p = 0.008), and the number of fibers (p = 0.017) were significantly lower in the diabetic group compared with controls. There was no difference between diabetic and healthy eyes in the mean number of corneal beadings both in the frame of analysis (p = 0.606) and for 0.1 mm of SBP nerve (p = 0.145). Regarding the BS, patients with T1DM had corneal beadings larger than controls (p = 0.036). Conclusions We found that the corneal beadings parameters are similar in healthy and T1DM individuals. Nevertheless, measuring the BS with our algorithm, we showed that corneal beadings are enlarged in patients affected by T1DM when compared with healthy controls. Identifying beading expansion in corneal nerve fiber using IVCM should become a useful tool to predict peripheral neuropathy at an early stage.
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Affiliation(s)
- Irene Abicca
- IRCCS–Fondazione Bietti, Rome, Italy
- *Correspondence: Irene Abicca
| | | | | | - Anna Maria Roszkowska
- Ophthalmology Clinic, Department of Biomedical Sciences, University of Messina, Messina, Italy
| | | | - Fabiana Picconi
- Unit of Endocrinology, Diabetes and Metabolism, S. Giovanni Calibita, Fatebenefratelli Hospital, Rome, Italy
| | - Simona Frontoni
- Unit of Endocrinology, Diabetes and Metabolism, S. Giovanni Calibita, Fatebenefratelli Hospital, Rome, Italy
- Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy
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Aloperine: A Potent Modulator of Crucial Biological Mechanisms in Multiple Diseases. Biomedicines 2022; 10:biomedicines10040905. [PMID: 35453655 PMCID: PMC9028564 DOI: 10.3390/biomedicines10040905] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2022] [Revised: 03/30/2022] [Accepted: 03/31/2022] [Indexed: 01/18/2023] Open
Abstract
Aloperine is an alkaloid found in the seeds and leaves of the medicinal plant Sophora alopecuroides L. It has been used as herbal medicine in China for centuries due to its potent anti-inflammatory, antioxidant, antibacterial, and antiviral properties. Recently, aloperine has been widely investigated for its therapeutic activities. Aloperine is proven to be an effective therapeutic agent against many human pathological conditions, including cancer, viral diseases, and cardiovascular and inflammatory disorders. Aloperine is reported to exert therapeutic effects through triggering various biological processes, including cell cycle arrest, apoptosis, autophagy, suppressing cell migration, and invasion. It has also been found to be associated with the modulation of various signaling pathways in different diseases. In this review, we summarize the most recent knowledge on the modulatory effects of aloperine on various critical biological processes and signaling mechanisms, including the PI3K, Akt, NF-κB, Ras, and Nrf2 pathways. These data demonstrate that aloperine is a promising therapeutic candidate. Being a potent modulator of signaling mechanisms, aloperine can be employed in clinical settings to treat various human disorders in the future.
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Busa P, Kuthati Y, Huang N, Wong CS. New Advances on Pathophysiology of Diabetes Neuropathy and Pain Management: Potential Role of Melatonin and DPP-4 Inhibitors. Front Pharmacol 2022; 13:864088. [PMID: 35496279 PMCID: PMC9039240 DOI: 10.3389/fphar.2022.864088] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2022] [Accepted: 03/14/2022] [Indexed: 12/14/2022] Open
Abstract
Pre-diabetes and diabetes are growing threats to the modern world. Diabetes mellitus (DM) is associated with comorbidities such as hypertension (83.40%), obesity (90.49%), and dyslipidemia (93.43%), creating a substantial burden on patients and society. Reductive and oxidative (Redox) stress level imbalance and inflammation play an important role in DM progression. Various therapeutics have been investigated to treat these neuronal complications. Melatonin and dipeptidyl peptidase IV inhibitors (DPP-4i) are known to possess powerful antioxidant and anti-inflammatory properties and have garnered significant attention in the recent years. In this present review article, we have reviewed the recently published reports on the therapeutic efficiency of melatonin and DPP-4i in the treatment of DM. We summarized the efficacy of melatonin and DPP-4i in DM and associated complications of diabetic neuropathy (DNP) and neuropathic pain. Furthermore, we discussed the mechanisms of action and their efficacy in the alleviation of oxidative stress in DM.
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Affiliation(s)
- Prabhakar Busa
- Department of Anesthesiology, Cathay General Hospital, Taipei, Taiwan
| | - Yaswanth Kuthati
- Department of Anesthesiology, Cathay General Hospital, Taipei, Taiwan
| | - Niancih Huang
- Department of Anesthesiology, Tri-Service General Hospital, Taipei, Taiwan
- Grauate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan
| | - Chih-Shung Wong
- Department of Anesthesiology, Cathay General Hospital, Taipei, Taiwan
- Department of Anesthesiology, Tri-Service General Hospital, Taipei, Taiwan
- Grauate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan
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Zhou T, Lee A, Lo ACY, Kwok JSWJ. Diabetic Corneal Neuropathy: Pathogenic Mechanisms and Therapeutic Strategies. Front Pharmacol 2022; 13:816062. [PMID: 35281903 PMCID: PMC8905431 DOI: 10.3389/fphar.2022.816062] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2021] [Accepted: 01/27/2022] [Indexed: 12/27/2022] Open
Abstract
Diabetes mellitus (DM) is a major global public health problem that can cause complications such as diabetic retinopathy, diabetic neuropathy, and diabetic nephropathy. Besides the reporting of reduction in corneal nerve density and decrease in corneal sensitivity in diabetic patients, there may be a subsequent result in delayed corneal wound healing and increased corneal infections. Despite being a potential cause of blindness, these corneal nerve changes have not gained enough attention. It has been proposed that corneal nerve changes may be an indicator for diabetic neuropathy, which can provide a window for early diagnosis and treatment. In this review, the authors aimed to give an overview of the relationship between corneal nerves and diabetic neuropathy as well as the underlying pathophysiological mechanisms of corneal nerve fiber changes caused by DM for improved prediction and prevention of diabetic neuropathy. In addition, the authors summarized current and novel therapeutic methods for delayed corneal wound healing, nerve protection and regeneration in the diabetic cornea.
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Affiliation(s)
- Ting Zhou
- Department of Ophthalmology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China
| | - Allie Lee
- Department of Ophthalmology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China
| | - Amy Cheuk Yin Lo
- Department of Ophthalmology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China
| | - Jeremy Sze Wai John Kwok
- Department of Ophthalmology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China
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Antioxidant and Anti-Inflammatory Activities of Phytochemicals from Ruellia tuberosa. J CHEM-NY 2022. [DOI: 10.1155/2022/4644641] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
In Vietnam, the aerial parts of Ruellia tuberosa L. are used to treat stress oxidation and inflammatory symptoms in diabetes mellitus. The present study was designed to determine the antioxidant and inflammatory inhibition activities of Ruellia tuberosa L. extract (RTE) and those of the isolated compounds by column chromatography. The crude ethanol extract and ethyl acetate fraction exhibited potent antioxidant activity in the 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) and 2,2-azinobis-(3-ethylbenzothiazoline-6-sulfonate) (ABTS) assays with an IC50 of 25.18 and 14.71 (DPPH test) and 18.22 and 15.27 µg/ml (ABTS test), respectively. The RTE contained high concentrations of polyphenols (308.21 mg GAE/g) and moderate concentrations of flavonoids (97.80 mg QE/g). In the anti-inflammatory screening assay, the crude ethanol extract, ethyl acetate, and methanol fractions suppressed the release of IL-6 and nitric oxide production, but the production of IL-10 was not enhanced in LPS-induced RAW 264.7 cells. Three potential anti-inflammatory compounds as hispidulin (6), physalin E (7), and physalin D (8) along with five other compounds named myricitrin (1), afzelin (2), apigenin (3), taraxerol (4), and lupeol (5) were isolated and identified from the ethyl acetate fraction. Physalin D (8) exhibited a strong, dose-dependent anti-inflammatory activity by inhibiting the production of IL-6 proinflammatory cytokines; however, the IL-10 expression was independent of its concentration in macrophages at noncytotoxic concentrations ranging from 5 to 40 μg/mL. Based on the data obtained, compounds 6–8 sourced from Ruellia tuberosa L are potentially bioactive compounds for the treatment of inflammation symptoms in type 2 diabetes mellitus.
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A Study of the Protective Effect of Bushen Huoxue Prescription on Cerebral Microvascular Endothelia Based on Proteomics and Bioinformatics. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2022; 2022:2545074. [PMID: 35035499 PMCID: PMC8758271 DOI: 10.1155/2022/2545074] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/11/2021] [Revised: 11/27/2021] [Accepted: 12/17/2021] [Indexed: 11/17/2022]
Abstract
Diabetic cognitive dysfunction is a serious complication of type 2 diabetes mellitus (T2DM), which can cause neurological and microvascular damage in the brain. At present, there is no effective treatment for this complication. Bushen Huoxue prescription (BSHX) is a newly formulated compound Chinese medicine containing 7 components. Previous research indicated that BSHX was neuroprotective against advanced glycosylation end product (AGE)-induced PC12 cell insult; however, the effect of BSHX on AGE-induced cerebral microvascular endothelia injury has not been studied. In the current research, we investigated the protective effects of BSHX on AGE-induced injury in bEnd.3 cells. Our findings revealed that BSHX could effectively protect bEnd.3 cells from apoptosis. Moreover, we analyzed the network regulation effect of BSHX on AGE-induced bEnd.3 cells injury at the proteomic level. The LC-MS/MS-based shotgun proteomics analysis showed BSHX negatively regulated multiple AGE-elicited proteins. Bioinformatics analysis revealed these differential proteins were involved in multiple processes, such as Foxo signaling pathway. Further molecular biology analysis confirmed that BSHX could downregulate the expression of FoxO1/3 protein and inhibit its nuclear transfer and inhibit the expression of downstream apoptotic protein Bim and the activation of caspase, so as to play a protective role in AGE-induced bEnd.3 injury. Taken together, these findings demonstrated the role of BSHX in the management of diabetic cerebral microangiopathy and provide some insights into the proteomics-guided pharmacological mechanism study of traditional Chinese Medicine.
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Clark GJ, Pandya K, Lau-Cam CA. Assessment of In Vitro Tests as Predictors of the Antioxidant Effects of Insulin, Metformin, and Taurine in the Brain of Diabetic Rats. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2022; 1370:243-256. [DOI: 10.1007/978-3-030-93337-1_24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
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Bassi-Dibai D, Santos-de-Araújo AD, Dibai-Filho AV, de Azevedo LFS, Goulart CDL, Luz GCP, Burke PR, Garcia-Araújo AS, Borghi-Silva A. Rehabilitation of Individuals With Diabetes Mellitus: Focus on Diabetic Myopathy. Front Endocrinol (Lausanne) 2022; 13:869921. [PMID: 35498435 PMCID: PMC9047902 DOI: 10.3389/fendo.2022.869921] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2022] [Accepted: 03/21/2022] [Indexed: 12/20/2022] Open
Abstract
Diabetes mellitus (DM) is a chronic metabolic disease characterized by high blood glucose levels, causing serious damage to the cardiovascular, respiratory, renal and other systems. The prevalence of type 2 diabetes mellitus (T2DM) was 6.28% in 2017, considering all age groups worldwide (prevalence rate of 6,059 cases per 100,000), and its global prevalence is projected to increase to 7,079 cases per 100,000 by 2030. Furthermore, these individuals are often affected by diabetic myopathy, which is the failure to preserve muscle mass and function in the course of DM. This happens in type 1 diabetes mellitus (T1DM) and T2DM. As skeletal muscle plays a key role in locomotion and glucose homeostasis, diabetic myopathy may contribute to additional complications of the disease. In addition, chronic hyperglycemia is associated with lung functional changes seen in patients with DM, such as reduced lung volumes and compliance, inspiratory muscle strength, and lung elastic recoil. Thus, the weakness of the inspiratory muscles, a consequence of diabetic myopathy, can influence exercise tolerance. Thus, moderate strength training in T2DM can contribute to the gain of peripheral muscle strength. Although the literature is robust on the loss of mass and consequent muscle weakness in diabetic myopathy, triggering pathophysiological factors, the impact on functional capacity, as well as the prescription of physical exercise for this condition deserves to be further explored. This review aims to explore the consequences of diabetic myopathy and its implication in rehabilitation from prescription to safety in the practice of physical exercises for these individuals.
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Affiliation(s)
| | | | | | | | - Cássia da Luz Goulart
- Postgraduate Program in Physical Therapy, Universidade Federal de São Carlos, São Carlos, Brazil
| | | | | | | | - Audrey Borghi-Silva
- Postgraduate Program in Physical Therapy, Universidade Federal de São Carlos, São Carlos, Brazil
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The Corneal Changes in Diabetic Patients. SERBIAN JOURNAL OF EXPERIMENTAL AND CLINICAL RESEARCH 2021. [DOI: 10.2478/sjecr-2020-0045] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Abstract
Diabetes mellitus (DM) represents a systemic disorder which afects different organs. Ocular complications of the DM are the worldwide leading cause of blindness. The most common complications are diabetic retinopathy, diabetic cataract, neovascular glaucoma. Recently many investigations point out that DM can cause comlications at ocular surface as well. Condition such as decreased corneal sensitivity, dry eye or neurotrophic corneal ulceraction are the main clinical manifestations of the diabetic keratopathy (DK). Untreated, these conditions can lead to serious visual acuity decrease. Pathological processes, based on chronic inflammation, due to chronic hyperglycemia, are the main step in the process of DK development. Adequate treatment of the main disease - DM is an imperative in maintaining the healthy cornea without subjective sensations of diabetic patients.
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Winiarska-Mieczan A, Tomaszewska E, Jachimowicz K. Antioxidant, Anti-Inflammatory, and Immunomodulatory Properties of Tea-The Positive Impact of Tea Consumption on Patients with Autoimmune Diabetes. Nutrients 2021; 13:nu13113972. [PMID: 34836227 PMCID: PMC8625657 DOI: 10.3390/nu13113972] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2021] [Revised: 11/03/2021] [Accepted: 11/05/2021] [Indexed: 01/08/2023] Open
Abstract
The physiological markers of autoimmune diabetes include functional disorders of the antioxidative system as well as progressing inflammation and the presence of autoantibodies. Even though people with type 1 diabetes show genetic predispositions facilitating the onset of the disease, it is believed that dietary factors can stimulate the initiation and progression of the disease. This paper analyses the possibility of using tea as an element of diet therapy in the treatment of type 1 diabetes. Based on information available in literature covering the last 10 years, the impact of regular tea consumption or diet supplements containing tea polyphenols on the oxidative status as well as inflammatory and autoimmune response of the organism was analyzed. Studies conducted on laboratory animals, human patients, and in vitro revealed positive effects of the consumption of tea or polyphenols isolated therefrom on the diabetic body. Few reports available in the literature pertain to the impact of tea on organisms affected by type 1 diabetes as most (over 85%) have focused on cases of type 2 diabetes. It has been concluded that by introducing tea into the diet, it is possible to alleviate some of the consequences of oxidative stress and inflammation, thus limiting their destructive impact on the patients' organisms, consequently improving their quality of life, regardless of the type of diabetes. Furthermore, elimination of inflammation should reduce the incidence of immune response. One should consider more widespread promotion of tea consumption by individuals genetically predisposed to diabetes, especially considering the drink's low price, easy availability, overall benefits to human health, and above all, the fact that it can be safely used over extended periods of time, regardless of the patient's age.
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Affiliation(s)
- Anna Winiarska-Mieczan
- Institute of Animal Nutrition and Bromatology, University of Life Sciences in Lublin, Akademicka St. 13, 20-950 Lublin, Poland;
- Correspondence: (A.W.-M.); (E.T.); Tel.: +48-81-445-67-44 (A.W.-M.); +48-81-445-69-63 (E.T.)
| | - Ewa Tomaszewska
- Department of Animal Physiology, Faculty of Veterinary Medicine, University of Life Sciences in Lublin, Akademicka St. 12, 20-950 Lublin, Poland
- Correspondence: (A.W.-M.); (E.T.); Tel.: +48-81-445-67-44 (A.W.-M.); +48-81-445-69-63 (E.T.)
| | - Karolina Jachimowicz
- Institute of Animal Nutrition and Bromatology, University of Life Sciences in Lublin, Akademicka St. 13, 20-950 Lublin, Poland;
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Abe K, Maeda Y, Matsuzaki C, Yokomizo H, Inoue T, Sonoda N, Ogawa Y, Inoguchi T. Bilirubin is inversely related to diabetic peripheral neuropathy assessed by sural nerve conduction study. J Diabetes Investig 2021; 12:2028-2035. [PMID: 33949141 PMCID: PMC8565409 DOI: 10.1111/jdi.13568] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2021] [Revised: 04/13/2021] [Accepted: 04/21/2021] [Indexed: 12/27/2022] Open
Abstract
AIMS/INTRODUCTION Diagnosis of diabetic peripheral neuropathy (DPN) depends on subjective findings, certain investigations for DPN risks have not been performed enough. Bilirubin protects against vascular complications by reducing oxidative stress in diabetes, but is not fully tested for DPN. This study aimed to evaluate sural nerve conduction impairments (SNCI) as an objective DPN marker and the contribution of bilirubin to SNCI. MATERIALS AND METHODS Using DPN-Check® , SNCI was defined as a decline of amplitude potential or conduction velocity below the normal limit in 150 inpatients with diabetes. The correlations between SNCI and conventional DPN diagnosis criteria, the incidence of diabetic retinopathy/nephropathy, biomarkers for atherosclerosis, cardiac function by ultrasonic cardiogram, and bilirubin were statistically tested, followed by the comparison of logistic regression models for SNCI to find confounders with bilirubin. RESULTS The incidence of SNCI was 72.0%. The sensitivity and specificity of SNCI for DPN prediagnosis by simplified criteria were 54.6 and 90.5%, respectively, and similarly corresponded with diabetic retinopathy and nephropathy (sensitivity 57.4 and 50.0%, respectively). SNCI significantly related to diabetes duration, declined estimated glomerular filtration rate, albuminuria and total bilirubin. SNCI incidence was attenuated in the higher bilirubin tertiles (89.8/65.3/54.8%, P < 0.001). Bilirubin was an independent inverse risk factor for SNCI, even after adjustment by known risk factors for DPN and markers for microvascular complications. CONCLUSIONS SNCI is a comprehensive marker for diabetic complications. We first showed the independent inverse relationship between bilirubin and SNCI through the independent pathway with other complications, provably reducing oxidative stress, as previously reported.
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Affiliation(s)
- Kentaro Abe
- Department of Medicine and Bioregulatory ScienceGraduate School of Medical SciencesKyushu UniversityFukuokaJapan
- Department of Diabetes, Endocrinology and MetabolismNational Hospital Organization Kokura Medical CenterKitakyusyuJapan
| | | | - Chitose Matsuzaki
- Department of Endocrine, Metabolism and DiabetesKyushu University HospitalFukuokaJapan
| | - Hisashi Yokomizo
- Department of Endocrine, Metabolism and DiabetesKyushu University HospitalFukuokaJapan
| | - Tomoaki Inoue
- Department of Endocrine, Metabolism and DiabetesKyushu University HospitalFukuokaJapan
| | - Noriyuki Sonoda
- Department of Medicine and Bioregulatory ScienceGraduate School of Medical SciencesKyushu UniversityFukuokaJapan
| | - Yoshihiro Ogawa
- Department of Medicine and Bioregulatory ScienceGraduate School of Medical SciencesKyushu UniversityFukuokaJapan
- Department of Endocrine, Metabolism and DiabetesKyushu University HospitalFukuokaJapan
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Dimova R, Chakarova N, Grozeva G, Tankova T. The relationship between endogenous secretory RAGE and cardiac autonomic function in prediabetes. Int J Clin Pract 2021; 75:e14769. [PMID: 34473880 DOI: 10.1111/ijcp.14769] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2021] [Accepted: 08/30/2021] [Indexed: 11/26/2022] Open
Abstract
AIMS The putative protective role of esRAGE for cardiac autonomic function (CAF) remains unclear. To address this question, the present study has assessed the relationship of serum AGEs, sRAGE and esRAGE, and tissue AGEs with CAF in a high-risk population without diabetes. MATERIAL AND METHODS This study enrolled 48 subjects of mean age 52.7 ± 11.2 years and mean BMI 28.4 ± 6.3 kg/m2 , divided into two groups according to glucose tolerance: 16 with normal glucose tolerance (NGT) and 24 with prediabetes. A standard oral glucose tolerance test (OGTT) was performed. The glucose tolerance was defined according to 2006 WHO criteria. Fasting, 120-minutes glucose, lipids, creatinine, and HbA1c were measured. eGFR was calculated (CKD-EPI). Fasting, 120-minutes insulin (ECLIA method), advanced glycation end products (AGEs), plasma-soluble receptor for AGE (sRAGE), and endogenous secreted isoform of the receptor for AGE (esRAGE), (ELISA method) were assessed. HOMA-IR was calculated. Tissue AGEs were assessed by skin autofluorescence (AGE-Reader, DiagnOpticsTM). CAF was evaluated with ANX 3.0 autonomic nervous-monitoring system (ANSAR), applying deep breathing, Valsalva, and standing. RESULTS There was a significant decline in CAF in prediabetes in comparison with NGT. Serum and tissue AGEs, sRAGE, and esRAGE levels were similar between groups. On the matrix analysis, both sympathetic and parasympathetic activities at baseline and after standing and sympathetic tone during Valsalva were positively related to esRAGE in prediabetes. Multivariate regression analysis showed that esRAGE is an independent contributor to sympathetic, parasympathetic, and total autonomic tone in prediabetes accounting for about 28%, 34%, and 35% of their variances, respectively. CONCLUSION Our results have demonstrated that CAF is decreased in prediabetes. esRAGE, but not sRAGE, is reciprocally related to CAF, probably opposing the negative effects of glycation.
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Affiliation(s)
- Rumyana Dimova
- Division of Diabetology, Department of Endocrinology, Medical University Sofia, Sofia, Bulgaria
| | - Nevena Chakarova
- Division of Diabetology, Department of Endocrinology, Medical University Sofia, Sofia, Bulgaria
| | - Greta Grozeva
- Division of Diabetology, Department of Endocrinology, Medical University Sofia, Sofia, Bulgaria
| | - Tsvetalina Tankova
- Division of Diabetology, Department of Endocrinology, Medical University Sofia, Sofia, Bulgaria
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Wong YH, Wong SH, Wong XT, Yi Yap Q, Yip KY, Wong LZ, Chellappan DK, Bhattamisra SK, Candasamy M. Genetic associated complications of type 2 Diabetes Mellitus: a review. Panminerva Med 2021; 64:274-288. [PMID: 34609116 DOI: 10.23736/s0031-0808.21.04285-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
According to the International Diabetes Federation, the number of adults (age of 20-79) being diagnosed with Diabetes Mellitus (DM) have increased from 285 million in year 2009 to 463 million in year 2019 which comprises of 95% Type 2 DM patient (T2DM). Research have claimed that genetic predisposition could be one of the factors causing T2DM complications. In addition, T2DMcomplications cause an incremental risk to mortality. Therefore, this article aims to discuss some complications of T2DM in and their genetic association. The complications that are discussed in this article are diabetic nephropathy, diabetes induced cardiovascular disease, diabetic neuropathy, Diabetic Foot Ulcer (DFU) and Alzheimer's disease. According to the information obtained, genes associated with diabetic nephropathy (DN) are gene GABRR1 and ELMO1 that cause injury to glomerular. Replication of genes FRMD3, CARS and MYO16/IRS2 shown to have link with DN. The increase of gene THBS2, NGAL, PIP, TRAF6 polymorphism, ICAM-1 encoded for rs5498 polymorphism and C667T increase susceptibility towards DN in T2DM patient. Genes associated with cardiovascular diseases are Adiponectin gene (ACRP30) and Apolipoprotein E (APOE) polymorphism gene with ξ2 allele. Haptoglobin (Hp) 1-1 genotype and Mitochondria Superoxide Dismutase 2 (SOD2) plays a role in cardiovascular events. As for genes related to diabetic neuropathy, Janus Kinase (JAK), mutation of SCN9A and TRPA1 gene and destruction of miRNA contribute to pathogenesis of diabetic neuropathy among T2DM patients. Expression of cytokine IL-6, IL-10, miR-146a are found to cause diabetic neuropathy. Besides, A1a16Va1 gene polymorphism, an oxidative stress influence was found as one of the gene factors. Diabetic retinopathy (DR) is believed to have association with Monocyte Chemoattractant Protein-1 (MCP-1) and Insulin-like Growth Factor 1 (IGF1). Over-expression of gene ENPP1, IL-6 pro-inflammatory cytokine, ARHGAP22's protein rs3844492 polymorphism and TLR4 heterozygous genotype are contributing to significant pathophysiological process causing DR, while research found increases level of UCP1 gene protects retina cells from oxidative stress. Diabetic Foot Ulcer (DFU) is manifested by slowing in reepithelialisation of keratinocyte, persistence wound inflammation and healing impairment. Reepithelialisation disturbance was caused by E2F3 gene, reduction of Tacl gene encoded substance P causing persistence inflammation while expression of MMp-9 polymorphism contributes to healing impairment. A decrease in HIF-1a gene expression leads to increased risk of pathogenesis, while downregulation of TLR2 increases severity of wound in DFU patients. SNPs alleles has been shown to have significant association between the genetic dispositions of T2DM and Alzheimer's disease (AD). The progression of AD can be due to the change in DNA methylation of CLOCK gene, followed with worsening of AD by APOE4 gene due to dyslipidaemia condition in T2DM patients. Insulin resistance is also a factor that contributes to pathogenesis of AD.
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Affiliation(s)
- Yee H Wong
- School of Pharmacy, International Medical University, Kuala Lumpur, Malaysia
| | - Shen H Wong
- School of Pharmacy, International Medical University, Kuala Lumpur, Malaysia
| | - Xiao T Wong
- School of Pharmacy, International Medical University, Kuala Lumpur, Malaysia
| | - Qiao Yi Yap
- School of Pharmacy, International Medical University, Kuala Lumpur, Malaysia
| | - Khar Y Yip
- School of Pharmacy, International Medical University, Kuala Lumpur, Malaysia
| | - Liang Z Wong
- School of Pharmacy, International Medical University, Kuala Lumpur, Malaysia
| | - Dinesh K Chellappan
- Department of Life Sciences, School of Pharmacy, International Medical University, Kuala Lumpur, Malaysia
| | - Subrat K Bhattamisra
- Department of Life Sciences, School of Pharmacy, International Medical University, Kuala Lumpur, Malaysia
| | - Mayuren Candasamy
- Department of Life Sciences, School of Pharmacy, International Medical University, Kuala Lumpur, Malaysia -
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Lin J, Liu G, Duan Z. The mechanism of esophagus dysmotility in diabetes and research progress of relating treatments. Expert Rev Gastroenterol Hepatol 2021; 15:919-927. [PMID: 34156876 DOI: 10.1080/17474124.2021.1945921] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
Introduction: Esophagus dysmotility is a crucial risk factor of gastroesophageal reflux disease (GERD), which is one of the most common diseases in digestive medicine globally. This review emphasizes the mechanisms of esophagus dysmotility in diabetes and summarizes more targeted treatments for these patients to avoid the overuse of proton pump inhibitors (PPIs).Areas covered: Diabetes mellitus (DM) is a clear factor that must not be neglected in the development of GERD. Previous studies have preliminarily researched the esophagus deterioration in diabetes. However, the multi-faceted mechanisms of esophagus dysmotility in diabetes need more studies. Besides, targeted treatments for these patients rather than conventional PPIs are urgently needed.Expert opinion: The treatments for GERD patients with diabetes should be further explored. Pharmacological approaches such as prokinetic agents, psychotherapy can be adopted. Meanwhile, it's feasible to explore non-drug treatments. For example, Electroacupuncture (EA) at Zusanli (ST-36) may be effective to protect the networks of intestinal cells of Cajal (ICCs) in diabetes. More effective approaches should be explored to achieve individualized treatment for these patients.
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Affiliation(s)
- Jiarong Lin
- The Second Department of Gastroenterology, The First Affiliated Hospital of Dalian Medical University, Dalian, China.,Laboratory of Integrated Chinese and Western Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Gongkai Liu
- School of Medicine, Nova Southeastern University, Davie, FL, USA
| | - Zhijun Duan
- The Second Department of Gastroenterology, The First Affiliated Hospital of Dalian Medical University, Dalian, China.,Laboratory of Integrated Chinese and Western Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian, China
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Cheng X, Zhao L, Ke T, Wang X, Cao L, Liu S, He J, Rong W. Celecoxib ameliorates diabetic neuropathy by decreasing apoptosis and oxidative stress in dorsal root ganglion neurons via the miR-155/COX-2 axis. Exp Ther Med 2021; 22:825. [PMID: 34149871 PMCID: PMC8200812 DOI: 10.3892/etm.2021.10257] [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] [Received: 02/11/2020] [Accepted: 03/29/2021] [Indexed: 12/12/2022] Open
Abstract
Celecoxib (CXB) is the only clinical cyclooxygenase-2 (COX-2) inhibitor. Oral administration of CXB in experimental diabetic mice effectively relieved the symptoms of diabetic neuropathy (DN); however, the molecular mechanism remains unclear. The present study aimed to investigate the potential molecular mechanisms of CXB in the treatment of DN. An in vitro cellular model of DN was produced by stimulating dorsal root ganglion (DRG) neurons with high glucose. Cell viability and apoptosis were assessed by Cell Counting Kit-8 assays and flow cytometry, respectively. Reactive oxygen species (ROS) kits, ELISA kits and western blotting were used to determine oxidative cellular damage. The expression level of microRNA (miR)-155 was analyzed by reverse transcription-quantitative PCR. The starBase database and dual-luciferase assays were performed to predict and determine the interaction between miR-155 and COX-2. Protein expression of neurotrophic factors, oxidative stress-related proteins and COX-2 were analyzed by western blotting. Incubation with high glucose led to a decrease in DRG neuron cell viability, facilitated apoptosis, downregulated NGF and BDNF expression, increased ROS and MDA generation and decreased SOD activity. Treatment with CXB significantly protected DRG neurons against high glucose-evoked damage. CXB promoted the expression of miR-155 and COX-2 was revealed to be a direct target of miR-155. Inhibition of COX-2 enhanced the protective effect of CXB on DRG neurons and that treatment with an miR-155 inhibitor partially rescued this effect. The present study demonstrated the involvement of the miR-155/COX-2 axis in the protective effect of CXB against high glucose-induced DN.
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Affiliation(s)
- Xiaoliang Cheng
- Department of Endocrinology, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650101, P.R. China
| | - Ling Zhao
- Department of Endocrinology, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650101, P.R. China
| | - Tingyu Ke
- Department of Endocrinology, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650101, P.R. China
| | - Xi Wang
- Department of Endocrinology, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650101, P.R. China
| | - Lijun Cao
- Department of Endocrinology, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650101, P.R. China
| | - Shuyan Liu
- Department of Endocrinology, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650101, P.R. China
| | - Jie He
- Department of Endocrinology, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650101, P.R. China
| | - Wei Rong
- Department of Neurology, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650101, P.R. China
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Niaz A, Adnan A, Bashir R, Mumtaz MW, Raza SA, Rashid U, Tan CP, Tan TB. The In Vitro α-Glucosidase Inhibition Activity of Various Solvent Fractions of Tamarix dioica and 1H-NMR Based Metabolite Identification and Molecular Docking Analysis. PLANTS 2021; 10:plants10061128. [PMID: 34199333 PMCID: PMC8227178 DOI: 10.3390/plants10061128] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/12/2021] [Revised: 04/15/2021] [Accepted: 04/19/2021] [Indexed: 11/16/2022]
Abstract
The Tamarix dioica (T. dioica) is widely used medicinal plant to cure many chronic ailments. T. dioica is being used to manage diabetes mellitus in traditional medicinal system; however, very little scientific evidence is available on this plant in this context. The current study involves the fractionation of crude methanolic extract of T. dioica using n-hexane, ethyl acetate, chloroform, and n-butanol. The screening for antioxidant activity using 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay was carried out. The in vitro antidiabetic potential was assessed by measuring α-glucosidase inhibition. Total phenolic and flavonoid contents were also determined for each fraction. The metabolites were identified using highly sensitive and emerging 1H-NMR technique. The results revealed the ethyl acetate fraction as the most potent with DPPH scavenging activity of 84.44 ± 0.21% and α-glucosidase inhibition with IC50 value of 122.81 ± 2.05 µg/mL. The total phenolic and flavonoid content values of 205.45 ± 1.36 mg gallic acid equivalent per gram dried extract and 156.85 ± 1.33 mg quercetin equivalent per gram dried extract were obtained for ethyl acetate fraction. The bucketing of 1H-NMR spectra identified 22 metabolites including some pharmacologically important like tamarixetin, tamaridone, quercetin, rutin, apigenin, catechin, kaempferol, myricetin and isorhamnetin. Leucine, lysine, glutamic acid, aspartic acid, serine, and tyrosine were the major amino acids identified in ethyl acetate fraction. The molecular docking analysis provided significant information on the binding affinity among secondary metabolites and α-glucosidase. These metabolites were most probably responsible for the antioxidant activity and α-glucosidase inhibitory potential of ethyl acetate fraction. The study ascertained the ethnomedicinal use of T. dioica to manage diabetes mellitus and may be a helpful lead towards naturopathic mode for anti-hyperglycemia.
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Affiliation(s)
- Aamir Niaz
- Department of Chemistry, GC University Lahore, Lahore 54000, Pakistan; (A.N.); (S.A.R.)
| | - Ahmad Adnan
- Department of Chemistry, GC University Lahore, Lahore 54000, Pakistan; (A.N.); (S.A.R.)
- Correspondence: (A.A.); or (U.R.); Tel.: +60-3-9769-7393 (U.R.); Fax: +60-3-9769-7006 (U.R.)
| | - Rashida Bashir
- Department of Chemistry, University of Education Lahore, Lahore 54000, Pakistan;
| | | | - Syed Ali Raza
- Department of Chemistry, GC University Lahore, Lahore 54000, Pakistan; (A.N.); (S.A.R.)
| | - Umer Rashid
- Institute of Advanced Technology, Universiti Putra Malaysia, Serdang 43400, Selangor, Malaysia
- Correspondence: (A.A.); or (U.R.); Tel.: +60-3-9769-7393 (U.R.); Fax: +60-3-9769-7006 (U.R.)
| | - Chin Ping Tan
- Department of Food Technology, Faculty of Food Science and Technology, Universiti Putra Malaysia, Serdang 43400, Selangor, Malaysia;
| | - Tai Boon Tan
- Department of Food Services and Management, Faculty of Food Science and Technology, Universiti Putra Malaysia, Serdang 43400, Selangor, Malaysia;
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Liu Y, Sun Y, Ewaleifoh O, Wei J, Mi R, Zhu J, Hoke A, Polydefkis M. Ethoxyquin is neuroprotective and partially prevents somatic and autonomic neuropathy in db/db mouse model of type 2 diabetes. Sci Rep 2021; 11:10749. [PMID: 34031437 PMCID: PMC8144207 DOI: 10.1038/s41598-021-89781-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2021] [Accepted: 04/29/2021] [Indexed: 11/24/2022] Open
Abstract
Ethoxyquin (EQ), a quinolone-based antioxidant, has demonstrated neuroprotective properties against several neurotoxic drugs in a phenotypic screening and is shown to protect axons in animal models of chemotherapy-induced peripheral neuropathy. We assessed the effects of EQ on peripheral nerve function in the db/db mouse model of type II diabetes. After a 7 week treatment period, 12-week-old db/db-vehicle, db/+ -vehicle and db/db-EQ treated animals were evaluated by nerve conduction, paw withdrawal against a hotplate, and fiber density in hindlimb footpads. We found that the EQ group had shorter paw withdrawal latency compared to vehicle db/db group. The EQ group scored higher in nerve conduction studies, compared to vehicle-treated db/db group. Morphology studies yielded similar results. To investigate the potential role of mitochondrial DNA (mtDNA) deletions in the observed effects of EQ, we measured total mtDNA deletion burden in the distal sciatic nerve. We observed an increase in total mtDNA deletion burden in vehicle-treated db/db mice compared to db/+ mice that was partially prevented in db/db-EQ treated animals. These results suggest that EQ treatment may exert a neuroprotective effect in diabetic neuropathy. The prevention of diabetes-induced mtDNA deletions may be a potential mechanism of the neuroprotective effects of EQ in diabetic neuropathy.
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Affiliation(s)
- Ying Liu
- Departments of Neurology, Johns Hopkins School of Medicine, Baltimore, MD, USA
| | - Yuan Sun
- Departments of Neurology, Johns Hopkins School of Medicine, Baltimore, MD, USA.,Liaoning Laboratory of Cancer Genomics, Department of Cell Biology, College of Basic Medical Science, Dalian Medical University, Dalian, China
| | - Osefame Ewaleifoh
- Departments of Neurology, Johns Hopkins School of Medicine, Baltimore, MD, USA.,Driskill Graduate Program, Northwestern University, Chicago, IL, USA
| | - Josh Wei
- Departments of Neurology, Johns Hopkins School of Medicine, Baltimore, MD, USA.,Parker University, Dallas, TX, USA
| | - Ruifa Mi
- Departments of Neurology, Johns Hopkins School of Medicine, Baltimore, MD, USA
| | - Jing Zhu
- Departments of Neurology, Johns Hopkins School of Medicine, Baltimore, MD, USA.,Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medical, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Ahmet Hoke
- Departments of Neurology, Johns Hopkins School of Medicine, Baltimore, MD, USA
| | - Michael Polydefkis
- Departments of Neurology, Johns Hopkins School of Medicine, Baltimore, MD, USA.
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Han JX, Wang H, Liang HH, Guo JX. Correlation of the retinopathy degree with the change of ocular surface and corneal nerve in patients with type 2 diabetes mellitus. Int J Ophthalmol 2021; 14:750-758. [PMID: 34012892 DOI: 10.18240/ijo.2021.05.17] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2020] [Accepted: 01/14/2021] [Indexed: 12/21/2022] Open
Abstract
AIM To investigate the change of ocular surface and corneal nerve and their correlation in patients suffering from type 2 diabetes mellitus under different degrees of retinopathy. METHODS Totally 129 type 2 diabetes mellitus patients (257 eyes) were included. They were divided into three groups: no diabetic retinopathy (NDR) group (33 cases, 66 eyes), non-proliferative diabetic retinopathy (NPDR) group (32 cases, 64 eyes), and proliferative diabetic retinopathy (PDR) group (34 cases, 67 eyes). Healthy normal individuals were enrolled as controls (30 cases, 60 eyes). Ocular Surface Disease Index (OSDI) questionnaire was completed by all subjects, and dry eye analyzer was applied to examine tear meniscus height (TMH), first tear break-up time (FTBUT), average tear break-up time (ATBUT), tear film lipid layer thickness classification, and meibomian gland loss (MGL) score. Corneal nerve fiber density (CNFD), corneal nerve branch density (CNBD), corneal nerve fiber length (CNFL), and corneal nerve fiber tortuosity (CNFT) were examined by in vivo confocal microscopy (IVCM). The differences and correlation among these parameters were analyzed. RESULTS Total OSDI score, TMH, FTBUT, ATBUT, tear film lipid layer thickness, MGL score, CNFD, CNBD, CNFL, and CNFT were statistically different among the four groups (P<0.05). In NDR group, CNFL was positively correlated with TMH (r=0.493, both P<0.01) and ATBUT (r=0.437, P<0.05). CNFL in NPDR group was positively correlated with TMH (r=0.642, P<0.01) and ATBUT (r=0.6, P<0.01). CNFL in PDR group was positively correlated with TMH (r=0.364, P<0.05) and ATBUT (r=0.589, P<0.01), with low negative correlation with MGL score (r=-0.331, P<0.05). CONCLUSION With the progression of diabetic retinopathy, TMH, BUT, lipid layer thickness, CNFL, CNFD, and CNBD gradually decreased, while total OSDI score, MGL score, and CNFT increased. CNFL is correlated with TMH and ATBUT in diabetic patients.
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Affiliation(s)
- Jia-Xin Han
- Xuzhou Medical University, Xuzhou 221002, Jiangsu Province, China
| | - He Wang
- Department of Ophthalmology, Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, Jiangsu Province, China
| | - Huan-Huan Liang
- Xuzhou Medical University, Xuzhou 221002, Jiangsu Province, China
| | - Jian-Xin Guo
- Department of Ophthalmology, Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, Jiangsu Province, China
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Genetic and Epigenomic Modifiers of Diabetic Neuropathy. Int J Mol Sci 2021; 22:ijms22094887. [PMID: 34063061 PMCID: PMC8124699 DOI: 10.3390/ijms22094887] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2021] [Revised: 04/29/2021] [Accepted: 05/03/2021] [Indexed: 12/18/2022] Open
Abstract
Diabetic neuropathy (DN), the most common chronic and progressive complication of diabetes mellitus (DM), strongly affects patients’ quality of life. DN could be present as peripheral, autonomous or, clinically also relevant, uremic neuropathy. The etiopathogenesis of DN is multifactorial, and genetic components play a role both in its occurrence and clinical course. A number of gene polymorphisms in candidate genes have been assessed as susceptibility factors for DN, and most of them are linked to mechanisms such as reactive oxygen species production, neurovascular impairments and modified protein glycosylation, as well as immunomodulation and inflammation. Different epigenomic mechanisms such as DNA methylation, histone modifications and non-coding RNA action have been studied in DN, which also underline the importance of “metabolic memory” in DN appearance and progression. In this review, we summarize most of the relevant data in the field of genetics and epigenomics of DN, hoping they will become significant for diagnosis, therapy and prevention of DN.
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