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1
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Fateh ST, Shiraseb F, Hajinasab MM, Noori S, Clark CCT, Mirzaei K. Interaction between 3-SNP genetic risk score and dietary fats intake on inflammatory markers among overweight and obese women. J Diabetes Metab Disord 2025; 24:80. [PMID: 40093786 PMCID: PMC11909376 DOI: 10.1007/s40200-024-01542-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2024] [Accepted: 09/14/2024] [Indexed: 03/19/2025]
Abstract
Objectives This study, for the first time, sought to investigate whether the interaction between the GRS consists of three SNPs (CAV-1, CRY-1, MC4R) and fat intake is associated with inflammatory markers among Iranian overweight and obese women. Methods This cross-sectional study was conducted with 246 overweight and obese women, aged 18-48 years. Three SNPs, including CAV-1 rs3807992, CRY-1 rs2287161, and MC4R rs17782313, were genotyped using PCR-RFLP to calculate the genetic risk score (GRS) for each participant. Dietary fat intake was measured using a validated semi-quantitative food frequency questionnaire (FFQ). C-reactive protein (CRP), interleukin-1β (IL-1β), transforming growth factor-β (TGF-β), monocyte chemoattractant protein-1 (MCP-1), plasminogen activator inhibitor-1 (PAI-1), and Galectin-3 (Gal-3) were assessed as the primary outcomes of the study. Results After controlling for confounding variables, a significant interaction between high total fat intake and high GRS, compared to the reference group, was found for TGF-β level (P-value: 0.028). A significant positive interaction between high GRS and high intakes of SFA intake (P-value: 0.013). A significant interaction between high GRS and high intakes of MUFA, compared to the reference group, was found for ghrelin level (P-value: 0.040) and MCP-1 level (P-value: 0.075). There was a significant interaction between high GRS and intakes of DHA, compared to the reference group, for Gal-3 level (P-value: 0.013) MCP-1 level (P-value: 0.020). Conclusions Consuming different types of fats can influence the interaction between GRS and inflammatory markers, suggesting further research is needed to fully understand this relationship. Supplementary information The online version contains supplementary material available at 10.1007/s40200-024-01542-z.
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Affiliation(s)
| | - Farideh Shiraseb
- Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Science (TUMS), Tehran University of Medical Sciences (TUMS), P.O. Box: 14155-6117, Tehran, Iran
| | - Mohammad Mahdi Hajinasab
- Department of Nutrition, Electronic Health and Statistics Surveillance Research Center, Science and Research Branch, Islamic Azad University, Tehran, Iran
| | - Sahar Noori
- Department of Nutrition, Science and Research Branch, Islamic Azad University, Tehran, Iran
| | - Cain C. T. Clark
- Centre for Intelligent Healthcare, Coventry University, CV1 5FB Coventry, U.K
| | - Khadijeh Mirzaei
- Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Science (TUMS), Tehran University of Medical Sciences (TUMS), P.O. Box: 14155-6117, Tehran, Iran
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2
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Shodry S, Hasan YTN, Ahdi IR, Ulhaq ZS. Gene targets with therapeutic potential in hepatocellular carcinoma. World J Gastrointest Oncol 2024; 16:4543-4547. [PMID: 39678796 PMCID: PMC11577361 DOI: 10.4251/wjgo.v16.i12.4543] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/27/2024] [Revised: 08/03/2024] [Accepted: 08/13/2024] [Indexed: 11/12/2024] Open
Abstract
Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide. Major treatments include liver transplantation, resection, and chemotherapy, but the 5-year recurrence rate remains high. Late diagnosis often prevents surgical intervention, contributing to poor patient survival rates. Carcinogenesis in HCC involves genetic alterations that drive the transformation of normal cells into malignant ones. Enhancer of zeste homolog 2 (EZH2), a key regulator of cell cycle progression, is frequently upregulated in HCC and is associated with advanced stages and poor prognosis, making it a potential biomarker. Additionally, signal transducer and activator of transcription 3, which binds to EZH2, affects disease staging and outcomes. Targeting EZH2 presents a promising therapeutic strategy. On the other hand, abnormal lipid metabolism is a hallmark of HCC and impacts prognosis. Fatty acid binding protein 5 is highly expressed in HCC tissues and correlates with key oncogenes, suggesting its potential as a biomarker. Other genes such as guanine monophosphate synthase, cell division cycle associated 5, and epidermal growth factor receptor provide insights into the molecular mechanisms of HCC, offering potential as biomarkers and therapeutic targets.
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Affiliation(s)
- Syifaus Shodry
- Faculty of Medicine and Health Sciences, Maulana Ibrahim Islamic State University of Malang, Malang 65144, Jawa Timur, Indonesia
| | - Yuliono Trika Nur Hasan
- Faculty of Medicine and Health Sciences, Maulana Ibrahim Islamic State University of Malang, Malang 65144, Jawa Timur, Indonesia
| | - Iwal Reza Ahdi
- Faculty of Medicine and Health Sciences, Maulana Ibrahim Islamic State University of Malang, Malang 65144, Jawa Timur, Indonesia
| | - Zulvikar Syambani Ulhaq
- Research Center for Preclinical and Clinical Medicine, National Research and Innovation Agency Republic of Indonesia, Cibinong 16911, Indonesia
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3
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Ulhaq ZS, Bittencourt GB, Soraya GV, Istifiani LA, Pamungkas SA, Ogino Y, Nurputra DK, Tse WKF. Association between glaucoma susceptibility with combined defects in mitochondrial oxidative phosphorylation and fatty acid beta oxidation. Mol Aspects Med 2024; 96:101238. [PMID: 38215610 DOI: 10.1016/j.mam.2023.101238] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2023] [Revised: 11/08/2023] [Accepted: 11/28/2023] [Indexed: 01/14/2024]
Abstract
Glaucoma is one of the leading causes of visual impairment and blindness worldwide, and is characterized by the progressive damage of retinal ganglion cells (RGCs) and the atrophy of the optic nerve head (ONH). The exact cause of RGC loss and optic nerve damage in glaucoma is not fully understood. The high energy demands of these cells imply a higher sensitivity to mitochondrial defects. Moreover, it has been postulated that the optic nerve is vulnerable towards damage from oxidative stress and mitochondrial dysfunction. To investigate this further, we conducted a pooled analysis of mitochondrial variants related to energy production, specifically focusing on oxidative phosphorylation (OXPHOS) and fatty acid β-oxidation (FAO). Our findings revealed that patients carrying non-synonymous (NS) mitochondrial DNA (mtDNA) variants within the OXPHOS complexes had an almost two-fold increased risk of developing glaucoma. Regarding FAO, our results demonstrated that longer-chain acylcarnitines (AC) tended to decrease, while shorter-chain AC tended to increase in patients with glaucoma. Furthermore, we observed that the knocking down cpt1a (a key rate-limiting enzyme involved in FAO) in zebrafish induced a degenerative process in the optic nerve and RGC, which resembled the characteristics observed in glaucoma. In conclusion, our study provides evidence that genes encoding mitochondrial proteins involved in energy metabolisms, such as OXPHOS and FAO, are associated with glaucoma. These findings contribute to a better understanding of the molecular mechanisms underlying glaucoma pathogenesis and may offer potential targets for therapeutic interventions in the future.
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Affiliation(s)
- Zulvikar Syambani Ulhaq
- Research Center for Pre-clinical and Clinical Medicine, National Research and Innovation Agency Republic of Indonesia, Cibinong, Indonesia; Laboratory of Developmental Disorders and Toxicology, Center for Promotion of International Education and Research, Faculty of Agriculture, Kyushu University, Fukuoka, Japan.
| | - Guido Barbieri Bittencourt
- Departamento de Psicologia Experimental, Instituto de Psicologia, Universidade de São Paulo, São Paulo, Brazil
| | - Gita Vita Soraya
- Department of Biochemistry, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia
| | - Lola Ayu Istifiani
- Department of Nutrition, Faculty of Health Sciences, Brawijaya University, Malang, Indonesia
| | | | - Yukiko Ogino
- Laboratory of Aquatic Molecular Developmental Biology, Center for Promotion of International Education and Research, Faculty of Agriculture, Kyushu University, Fukuoka, Japan
| | | | - William Ka Fai Tse
- Laboratory of Developmental Disorders and Toxicology, Center for Promotion of International Education and Research, Faculty of Agriculture, Kyushu University, Fukuoka, Japan.
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4
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Garmendia JV, De Sanctis CV, Das V, Annadurai N, Hajduch M, De Sanctis JB. Inflammation, Autoimmunity and Neurodegenerative Diseases, Therapeutics and Beyond. Curr Neuropharmacol 2024; 22:1080-1109. [PMID: 37898823 PMCID: PMC10964103 DOI: 10.2174/1570159x22666231017141636] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2023] [Revised: 07/13/2023] [Accepted: 08/03/2023] [Indexed: 10/30/2023] Open
Abstract
Neurodegenerative disease (ND) incidence has recently increased due to improved life expectancy. Alzheimer's (AD) or Parkinson's disease (PD) are the most prevalent NDs. Both diseases are poly genetic, multifactorial and heterogenous. Preventive medicine, a healthy diet, exercise, and controlling comorbidities may delay the onset. After the diseases are diagnosed, therapy is needed to slow progression. Recent studies show that local, peripheral and age-related inflammation accelerates NDs' onset and progression. Patients with autoimmune disorders like inflammatory bowel disease (IBD) could be at higher risk of developing AD or PD. However, no increase in ND incidence has been reported if the patients are adequately diagnosed and treated. Autoantibodies against abnormal tau, β amyloid and α- synuclein have been encountered in AD and PD and may be protective. This discovery led to the proposal of immune-based therapies for AD and PD involving monoclonal antibodies, immunization/ vaccines, pro-inflammatory cytokine inhibition and anti-inflammatory cytokine addition. All the different approaches have been analysed here. Future perspectives on new therapeutic strategies for both disorders are concisely examined.
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Affiliation(s)
- Jenny Valentina Garmendia
- Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, Olomouc, The Czech Republic
| | - Claudia Valentina De Sanctis
- Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, Olomouc, The Czech Republic
| | - Viswanath Das
- Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, Olomouc, The Czech Republic
- The Czech Advanced Technology and Research Institute (Catrin), Palacky University, Olomouc, The Czech Republic
| | - Narendran Annadurai
- Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, Olomouc, The Czech Republic
| | - Marián Hajduch
- Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, Olomouc, The Czech Republic
- The Czech Advanced Technology and Research Institute (Catrin), Palacky University, Olomouc, The Czech Republic
| | - Juan Bautista De Sanctis
- Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, Olomouc, The Czech Republic
- The Czech Advanced Technology and Research Institute (Catrin), Palacky University, Olomouc, The Czech Republic
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Chen K, Wang H, Ilyas I, Mahmood A, Hou L. Microglia and Astrocytes Dysfunction and Key Neuroinflammation-Based Biomarkers in Parkinson's Disease. Brain Sci 2023; 13:brainsci13040634. [PMID: 37190599 DOI: 10.3390/brainsci13040634] [Citation(s) in RCA: 20] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2023] [Revised: 03/26/2023] [Accepted: 04/03/2023] [Indexed: 05/17/2023] Open
Abstract
Parkinson's disease (PD) is the second most common neurodegenerative disease, with symptoms such as tremor, bradykinesia with rigidity, and depression appearing in the late stage of life. The key hallmark of PD is the loss or death of dopaminergic neurons in the region substantia nigra pars compacta. Neuroinflammation plays a key role in the etiology of PD, and the contribution of immunity-related events spurred the researchers to identify anti-inflammatory agents for the treatment of PD. Neuroinflammation-based biomarkers have been identified for diagnosing PD, and many cellular and animal models have been used to explain the underlying mechanism; however, the specific cause of neuroinflammation remains uncertain, and more research is underway. So far, microglia and astrocyte dysregulation has been reported in PD. Patients with PD develop neural toxicity, inflammation, and inclusion bodies due to activated microglia and a-synuclein-induced astrocyte conversion into A1 astrocytes. Major phenotypes of PD appear in the late stage of life, so there is a need to identify key early-stage biomarkers for proper management and diagnosis. Studies are under way to identify key neuroinflammation-based biomarkers for early detection of PD. This review uses a constructive analysis approach by studying and analyzing different research studies focused on the role of neuroinflammation in PD. The review summarizes microglia, astrocyte dysfunction, neuroinflammation, and key biomarkers in PD. An approach that incorporates multiple biomarkers could provide more reliable diagnosis of PD.
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Affiliation(s)
- Kun Chen
- Department of Neurosurgery, Changzheng Hospital, Naval Medical University, Shanghai 200003, China
| | - Haoyang Wang
- Department of Neurosurgery, Changzheng Hospital, Naval Medical University, Shanghai 200003, China
| | - Iqra Ilyas
- National Centre of Excellence in Molecular Biology (CEMB), University of The Punjab, Lahore 53700, Pakistan
| | - Arif Mahmood
- Center for Medical Genetics and Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha 410078, China
| | - Lijun Hou
- Department of Neurosurgery, Changzheng Hospital, Naval Medical University, Shanghai 200003, China
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Isik S, Yeman Kiyak B, Akbayir R, Seyhali R, Arpaci T. Microglia Mediated Neuroinflammation in Parkinson’s Disease. Cells 2023; 12:cells12071012. [PMID: 37048085 PMCID: PMC10093562 DOI: 10.3390/cells12071012] [Citation(s) in RCA: 102] [Impact Index Per Article: 51.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2023] [Revised: 03/16/2023] [Accepted: 03/21/2023] [Indexed: 03/29/2023] Open
Abstract
Parkinson’s Disease (PD) is the second most common neurodegenerative disorder seen, especially in the elderly. Tremor, shaking, movement problems, and difficulty with balance and coordination are among the hallmarks, and dopaminergic neuronal loss in substantia nigra pars compacta of the brain and aggregation of intracellular protein α-synuclein are the pathological characterizations. Neuroinflammation has emerged as an involving mechanism at the initiation and development of PD. It is a complex network of interactions comprising immune and non-immune cells in addition to mediators of the immune response. Microglia, the resident macrophages in the CNS, take on the leading role in regulating neuroinflammation and maintaining homeostasis. Under normal physiological conditions, they exist as “homeostatic” but upon pathological stimuli, they switch to the “reactive state”. Pro-inflammatory (M1) and anti-inflammatory (M2) phenotypes are used to classify microglial activity with each phenotype having its own markers and released mediators. When M1 microglia are persistent, they will contribute to various inflammatory diseases, including neurodegenerative diseases, such as PD. In this review, we focus on the role of microglia mediated neuroinflammation in PD and also signaling pathways, receptors, and mediators involved in the process, presenting the studies that associate microglia-mediated inflammation with PD. A better understanding of this complex network and interactions is important in seeking new therapies for PD and possibly other neurodegenerative diseases.
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Affiliation(s)
- Sevim Isik
- Department of Molecular Biology and Genetics, Faculty of Engineering and Natural Sciences, Uskudar University, Uskudar, Istanbul 34662, Turkey
- Stem Cell Research and Application Center (USKOKMER), Uskudar University, Uskudar, Istanbul 34662, Turkey
- Correspondence: ; Tel.: +90-216-400-2222 (ext. 2462)
| | - Bercem Yeman Kiyak
- Stem Cell Research and Application Center (USKOKMER), Uskudar University, Uskudar, Istanbul 34662, Turkey
- Department of Molecular Medicine, Institute of Hamidiye Health Sciences, University of Health Sciences, Uskudar, Istanbul 34668, Turkey
| | - Rumeysa Akbayir
- Stem Cell Research and Application Center (USKOKMER), Uskudar University, Uskudar, Istanbul 34662, Turkey
- Department of Molecular Biology, Institute of Science, Uskudar University, Uskudar, Istanbul 34662, Turkey
| | - Rama Seyhali
- Stem Cell Research and Application Center (USKOKMER), Uskudar University, Uskudar, Istanbul 34662, Turkey
- Department of Molecular Biology, Institute of Science, Uskudar University, Uskudar, Istanbul 34662, Turkey
| | - Tahire Arpaci
- Stem Cell Research and Application Center (USKOKMER), Uskudar University, Uskudar, Istanbul 34662, Turkey
- Department of Molecular Biology, Institute of Science, Uskudar University, Uskudar, Istanbul 34662, Turkey
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7
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Yi M, Li J, Jian S, Li B, Huang Z, Shu L, Zhang Y. Quantitative and causal analysis for inflammatory genes and the risk of Parkinson's disease. Front Immunol 2023; 14:1119315. [PMID: 36926335 PMCID: PMC10011457 DOI: 10.3389/fimmu.2023.1119315] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2022] [Accepted: 02/08/2023] [Indexed: 03/08/2023] Open
Abstract
Background The dysfunction of immune system and inflammation contribute to the Parkinson's disease (PD) pathogenesis. Cytokines, oxidative stress, neurotoxin and metabolism associated enzymes participate in neuroinflammation in PD and the genes involved in them have been reported to be associated with the risk of PD. In our study, we performed a quantitative and causal analysis of the relationship between inflammatory genes and PD risk. Methods Standard process was performed for quantitative analysis. Allele model (AM) was used as primary outcome analysis and dominant model (DM) and recessive model (RM) were applied to do the secondary analysis. Then, for those genes significantly associated with the risk of PD, we used the published GWAS summary statistics for Mendelian Randomization (MR) to test the causal analysis between them. Results We included 36 variants in 18 genes for final pooled analysis. As a result, IL-6 rs1800795, TNF-α rs1799964, PON1 rs854560, CYP2D6 rs3892097, HLA-DRB rs660895, BST1 rs11931532, CCDC62 rs12817488 polymorphisms were associated with the risk of PD statistically with the ORs ranged from 0.66 to 3.19 while variants in IL-1α, IL-1β, IL-10, MnSOD, NFE2L2, CYP2E1, NOS1, NAT2, ABCB1, HFE and MTHFR were not related to the risk of PD. Besides, we observed that increasing ADP-ribosyl cyclase (coded by BST1) had causal effect on higher PD risk (OR[95%CI] =1.16[1.10-1.22]) while PON1(coded by PON1) shown probably protective effect on PD risk (OR[95%CI] =0.81[0.66-0.99]). Conclusion Several polymorphisms from inflammatory genes of IL-6, TNF-α, PON1, CYP2D6, HLA-DRB, BST1, CCDC62 were statistically associated with the susceptibility of PD, and with evidence of causal relationships for ADP-ribosyl cyclase and PON1 on PD risk, which may help understand the mechanisms and pathways underlying PD pathogenesis.
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Affiliation(s)
- Minhan Yi
- Department of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, China.,School of Life Sciences, Central South University, Changsha, Hunan, China.,National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Jiaxin Li
- Department of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, China.,National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China.,Xiangya School of Medicine, Central South University, Changsha, Hunan, China
| | - Shijie Jian
- School of Life Sciences, Central South University, Changsha, Hunan, China
| | - Binbin Li
- Department of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, China.,Xiangya School of Medicine, Central South University, Changsha, Hunan, China
| | - Zini Huang
- Bangor College, Central South University of Forestry and Technology, Changsha, Hunan, China
| | - Li Shu
- National Health Commission Key Laboratory for Birth Defect Research and Prevention, Hunan Provincial Maternal and Child Health Care Hospital, Changsha, Hunan, China
| | - Yuan Zhang
- Department of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, China.,National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
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Su J, Deng Y, Cai B, Teng S, Zhang S, Liu Y, Lin J, Yang Q, Zeng D, Zhao X, Chen T. PI3K polymorphism in patients with sporadic Parkinson's disease. Medicine (Baltimore) 2022; 101:e32349. [PMID: 36595764 PMCID: PMC9794324 DOI: 10.1097/md.0000000000032349] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
Abstract
Parkinson's disease (PD) is a common irreversible neurodegenerative disease associated with cognitive impairment. To investigate the serum level of phosphatidylinositol-3-kinase (PI3K) and the distribution of the genotypes and alleles of 3 PI3K single-nucleotide polymorphisms (RS37,30,087, RS37,30,088, and RS37,30,089) in PD patients with different clinical characteristics. A total of 54 PD patients and 50 healthy individuals were recruited. The serum PI3K level was measured using the enzyme-linked immunosorbent assay. The severity of PD was assessed using the modified Hoehn-Yahr scale. The cognitive function of PD patients was evaluated using the Mini-Mental State Examination scale and the Montreal Cognitive Assessment. The distribution of the alleles and genotypes of PI3K single-nucleotide polymorphisms (SNPs) was calculated using the Hardy-Weinberg equilibrium. PD patients showed a significantly higher serum level of PI3K compared to healthy individuals. Increased serum PI3K level was observed in PD patients with more severe disease, longer disease duration, and impaired cognitive function. Additionally, no significant differences were observed in the distributions of the genotypes and alleles of 3 PI3K SNPs between PD patients with normal cognitive function and those with cognitive impairment. PD patients with different levels of disease severity, disease duration, and cognitive function had significantly different serum levels of PI3K. However, the PI3K SNPs in patients with normal cognitive function were not significantly different from those in patients with cognitive impairment. These findings contribute to a better understanding of the roles of PI3K and SNPs of the PI3K gene in PD.
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Affiliation(s)
- Jiali Su
- Department of Neurology, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, Hainan, China
| | - Yidong Deng
- Department of Neurology, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, Hainan, China
| | - Benchi Cai
- Department of Neurology, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, Hainan, China
| | - Si Teng
- Department of Neurology, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, Hainan, China
| | - Shan Zhang
- Department of Neurology, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, Hainan, China
| | - Yanhui Liu
- Department of Neurology, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, Hainan, China
| | - Jie Lin
- Department of Neurology, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, Hainan, China
| | - Qiang Yang
- Department of Neurology, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, Hainan, China
| | - Danting Zeng
- Department of Neurology, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, Hainan, China
| | - Xiuying Zhao
- Department of Neurology, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, Hainan, China
| | - Tao Chen
- Department of Neurology, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, Hainan, China
- * Correspondence: Tao Chen, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, No.19 Xiuhua Road, Haikou, Hainan 570311, China (e-mail: )
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9
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Arena G, Sharma K, Agyeah G, Krüger R, Grünewald A, Fitzgerald JC. Neurodegeneration and Neuroinflammation in Parkinson's Disease: a Self-Sustained Loop. Curr Neurol Neurosci Rep 2022; 22:427-440. [PMID: 35674870 PMCID: PMC9174445 DOI: 10.1007/s11910-022-01207-5] [Citation(s) in RCA: 41] [Impact Index Per Article: 13.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/02/2022] [Indexed: 02/06/2023]
Abstract
PURPOSE OF REVIEW Neuroinflammation plays a significant role in Parkinson's disease (PD) etiology along with mitochondrial dysfunction and impaired proteostasis. In this context, mechanisms related to immune response can act as modifiers at different steps of the neurodegenerative process and justify the growing interest in anti-inflammatory agents as potential disease-modifying treatments in PD. The discovery of inherited gene mutations in PD has allowed researchers to develop cellular and animal models to study the mechanisms of the underlying biology, but the original cause of neuroinflammation in PD is still debated to date. RECENT FINDINGS Cell autonomous alterations in neuronal cells, including mitochondrial damage and protein aggregation, could play a role, but recent findings also highlighted the importance of intercellular communication at both local and systemic level. This has given rise to debate about the role of non-neuronal cells in PD and reignited intense research into the gut-brain axis and other non-neuronal interactions in the development of the disease. Whatever the original trigger of neuroinflammation in PD, what appears quite clear is that the aberrant activation of glial cells and other components of the immune system creates a vicious circle in which neurodegeneration and neuroinflammation nourish each other. In this review, we will provide an up-to-date summary of the main cellular alterations underlying neuroinflammation in PD, including those induced by environmental factors (e.g. the gut microbiome) and those related to the genetic background of affected patients. Starting from the lesson provided by familial forms of PD, we will discuss pathophysiological mechanisms linked to inflammation that could also play a role in idiopathic forms. Finally, we will comment on the potential clinical translatability of immunobiomarkers identified in PD patient cohorts and provide an update on current therapeutic strategies aimed at overcoming or preventing inflammation in PD.
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Affiliation(s)
- G Arena
- Luxembourg Center for Systems Biomedicine (LCSB), University of Luxembourg, Esch-sur-Alzette, Luxembourg.
| | - K Sharma
- Department of Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany
| | - G Agyeah
- Luxembourg Center for Systems Biomedicine (LCSB), University of Luxembourg, Esch-sur-Alzette, Luxembourg
| | - R Krüger
- Luxembourg Center for Systems Biomedicine (LCSB), University of Luxembourg, Esch-sur-Alzette, Luxembourg
- Transversal Translational Medicine, Luxembourg Institute of Health, Strassen, Luxembourg
- Centre Hospitalier de Luxembourg (CHL), Luxembourg, Luxembourg
| | - A Grünewald
- Luxembourg Center for Systems Biomedicine (LCSB), University of Luxembourg, Esch-sur-Alzette, Luxembourg
- Institute of Neurogenetics, University of Lübeck, Lübeck, Germany
| | - J C Fitzgerald
- Department of Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany
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10
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Ulhaq ZS, Soraya GV, Dewi NA, Wulandari LR. The prevalence of anxiety symptoms and disorders among ophthalmic disease patients. Ther Adv Ophthalmol 2022; 14:25158414221090100. [PMID: 35464342 PMCID: PMC9021519 DOI: 10.1177/25158414221090100] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2021] [Accepted: 03/09/2022] [Indexed: 12/26/2022] Open
Abstract
Background: Progressive and irreversible vision loss has been shown to place a patient at risk of mental health problems such as anxiety. However, the reported prevalence of anxiety symptoms and disorders among eye disease patients vary across studies. Thus, this study aims to clarify the estimated prevalence of anxiety symptoms and disorders among ophthalmic disease patients. Methods: Relevant studies on the prevalence of anxiety symptoms and disorders among eye disease patients were collected through international databases, PubMed, Scopus, and Web of Science. A random-effects model was used to determine the pooled prevalence of anxiety symptoms and disorders among ophthalmic disease patients. Results: The 95 included studies yielded a pooled prevalence of 31.2% patients with anxiety symptoms and 19.0% with anxiety disorders among subjects with ophthalmic disease. Pediatric patients were more anxious (58.6%) than adults (29%). Anxiety symptoms were most prevalent in uveitis (53.5%), followed by dry eye disease (DED, 37.2%), retinitis pigmentosa (RP, 36.5%), diabetic retinopathy (DR, 31.3%), glaucoma (30.7%), myopia (24.7%), age-related macular degeneration (AMD, 21.6%), and cataract (21.2%) patients. Anxiety disorders were most prevalent in thyroid eye disease (TED, 28.9%), followed by glaucoma (22.2%) and DED (11.4%). When compared with healthy controls, there was a twofold increase on the prevalence of anxiety symptoms (OR = 1.912, 95% CI 1.463–2.5, p < 0.001) and anxiety disorders (OR = 2.281, 95% CI 1.168–4.454, p = 0.016). Conclusion: Anxiety symptoms and disorders are common problems associated with ophthalmic disease patients. Thus, comprehensive and appropriate treatments are necessary for treating anxiety symptoms and disorders among ophthalmic disease patients.
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Affiliation(s)
- Zulvikar Syambani Ulhaq
- Research Center for Pre-Clinical and Clinical Medicine, National Research and Innovation Agency Republic of Indonesia, Cibinong, Indonesia
| | - Gita Vita Soraya
- Department of Biochemistry, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia
| | - Nadia Artha Dewi
- Department of Ophthalmology, Faculty of Medicine, Brawijaya University, Malang, Indonesia
| | - Lely Retno Wulandari
- Department of Ophthalmology, Faculty of Medicine, Brawijaya University, Malang, Indonesia
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Ulhaq ZS, Soraya GV, Garcia CP. Implication of the
LINGO2 gene in the predisposition to movement disorders. BRAIN SCIENCE ADVANCES 2021. [DOI: 10.26599/bsa.2021.9050018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022] Open
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12
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Ulhaq ZS, Garcia CP. Estrogen receptor beta (ESR2) gene polymorphism and susceptibility to dementia. Acta Neurol Belg 2021; 121:1281-1293. [PMID: 32335869 DOI: 10.1007/s13760-020-01360-z] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2019] [Accepted: 04/15/2020] [Indexed: 12/13/2022]
Abstract
Strong evidence supports the involvement of sex steroid hormones in the development and progression of dementia. Attention has been largely focused on the association between genetic variants of estrogen receptor alpha (ERα, ESR1) with dementia, although several studies indicate that ERβ is predominantly expressed in the brain. Interestingly, however, a limited number of studies evaluate the role of ERβ (ESR2) in dementia. Therefore, a meta-analysis was conducted to clarify the association between ESR2 genetic polymorphisms and the risk of dementia. All the relevant studies evaluating ESR2 genetic polymorphisms and dementia were identified through online databases. In total, 14 studies including 20,609 subjects were analyzed. Collectively, it was found that a combined data set of ESR2 polymorphisms was not associated with dementia risk. Interestingly, ESR2 rs4986938 polymorphism is significantly associated with dementia in the Asian population (OR = 0.73, 95% CI 0.59-0.91, P = 0.006). The carrier of A allele in rs4986938 exhibits a protective effect against dementia (A vs. G, OR = 0.6633, P = 0.012; AA + GA vs. GG, OR = 0.6499, P = 0.014; GA vs. AA + GG, OR = 0.6672, P = 0.025; GA vs. GG, OR = 0.6617, P = 0.022). In conclusion, our study suggests that ESR2 genetic polymorphisms are not significantly associated with dementia risk. ESR2 rs4986938 may have potential as a genetic marker for dementia in the Asian population. However, further studies need to verify this conclusion.
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Affiliation(s)
- Zulvikar Syambani Ulhaq
- Department of Biomedical Science, Faculty of Medicine and Health Sciences, Maulana Malik Ibrahim Islamic State University of Malang, Batu, East Java, 65151, Indonesia.
| | - Cristian Peinado Garcia
- Department of General Surgery, Weston General Hospital, Grange Rd, Weston-super-Mare, BS23 4QT, UK
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13
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Ulhaq ZS, Soraya GV. Anti-IL-6 receptor antibody treatment for severe COVID-19 and the potential implication of IL-6 gene polymorphisms in novel coronavirus pneumonia. ACTA ACUST UNITED AC 2020; 155:548-556. [PMID: 33521302 PMCID: PMC7832797 DOI: 10.1016/j.medcle.2020.07.014] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2020] [Accepted: 07/03/2020] [Indexed: 12/17/2022]
Affiliation(s)
- Zulvikar Syambani Ulhaq
- Department of Biochemistry, Faculty of Medicine and Health Sciences, Maulana Malik Ibrahim Islamic State University of Malang, Batu, East Java 65151, Indonesia
| | - Gita Vita Soraya
- Department of Biochemistry, Faculty of Medicine, Hasanuddin University, Makassar, South Sulawesi 90245, Indonesia
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Ulhaq Z. Vitamin D and its receptor polymorphisms are associated with glaucoma. J Fr Ophtalmol 2020; 43:1009-1019. [DOI: 10.1016/j.jfo.2020.02.016] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2020] [Revised: 01/27/2020] [Accepted: 02/14/2020] [Indexed: 02/07/2023]
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15
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Ulhaq ZS, Soraya GV, Budu, Wulandari LR. The role of IL-6-174 G/C polymorphism and intraocular IL-6 levels in the pathogenesis of ocular diseases: a systematic review and meta-analysis. Sci Rep 2020; 10:17453. [PMID: 33060644 PMCID: PMC7566646 DOI: 10.1038/s41598-020-74203-9] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2020] [Accepted: 09/26/2020] [Indexed: 02/08/2023] Open
Abstract
Interleukin-6 (IL-6) is one of the key regulators behind the inflammatory and pathological process associated with ophthalmic diseases. The role of IL-6-174 G/C polymorphism as well as intraocular IL-6 levels among various eye disease patients differ across studies and has not been systematically reviewed. Thus, this study aims to provide a summary to understand the relationship between IL-6 and ophthalmic disease. In total, 8,252 and 11,014 subjects for IL-6-174 G/C and intraocular levels of IL-6, respectively, were retrieved from PubMed, Scopus and Web of Science. No association was found between IL-6-174 G/C polymorphisms with ocular diseases. Subgroup analyses revealed a suggestive association between the GC genotype of IL-6-174 G/C with proliferative diabetic retinopathy (PDR). Further, the level of intraocular IL-6 among ocular disease patients in general was found to be higher than the control group [standardized mean difference (SMD) = 1.41, 95% confidence interval (CI) 1.24-1.58, P < 0.00001]. Closer examination through subgroup analyses yielded similar results in several ocular diseases. This study thus indicates that the IL-6-174 G/C polymorphism does not predispose patients to ocular disease, although the GC genotype is likely to be a genetic biomarker for PDR. Moreover, intraocular IL-6 concentrations are related to the specific manifestations of the ophthalmic diseases. Further studies with larger sample sizes are warranted to confirm this conclusion.
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Affiliation(s)
- Zulvikar Syambani Ulhaq
- Department of Biochemistry, Faculty of Medicine and Health Sciences, Maulana Malik Ibrahim State Islamic University of Malang, Batu, East Java, 65151, Indonesia.
| | - Gita Vita Soraya
- Department of Biochemistry, Faculty of Medicine, Hasanuddin University, Makassar, South Sulawesi, Indonesia
| | - Budu
- Department of Ophthalmology, Faculty of Medicine, Hasanuddin University, Makassar, South Sulawesi, Indonesia
| | - Lely Retno Wulandari
- Department of Ophthalmology, Faculty of Medicine, Brawijaya University, Malang, East Java, Indonesia
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Ulhaq ZS. Comment on the assessment of "Association of interleukin-6 gene polymorphisms and glaucoma: systematic review and meta-analysis". Eur J Ophthalmol 2020; 31:2171-2172. [PMID: 32998541 DOI: 10.1177/1120672120962049] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Affiliation(s)
- Zulvikar Syambani Ulhaq
- Department of Biochemistry, Faculty of Medicine and Health Sciences, Maulana Malik Ibrahim State Islamic University of Malang, Batu, East Java, Indonesia
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Ulhaq ZS, Soraya GV. [Anti-IL-6 receptor antibody treatment for severe COVID-19 and the potential implication of IL-6 gene polymorphisms in novel coronavirus pneumonia]. Med Clin (Barc) 2020; 155:548-556. [PMID: 32950258 PMCID: PMC7351402 DOI: 10.1016/j.medcli.2020.07.002] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2020] [Revised: 06/30/2020] [Accepted: 07/03/2020] [Indexed: 12/17/2022]
Affiliation(s)
- Zulvikar Syambani Ulhaq
- Department of Biochemistry, Faculty of Medicine and Health Sciences, Maulana Malik Ibrahim Islamic State University of Malang, Batu, East Java 65151, Indonesia.
| | - Gita Vita Soraya
- Department of Biochemistry, Faculty of Medicine, Hasanuddin University, Makassar, South Sulawesi 90245, Indonesia
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