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Zheng Z, Xu S, Zhu J, Yang Q, Ye H, Li M, Zhang X, Liu H, Cheng Y, Zou Y, Lu Y, Wang P. Disease burden of cancers attributable to high fasting plasma glucose from 1990 to 2021 and projections until 2031 in China. Cancer Epidemiol 2025; 94:102725. [PMID: 39708577 DOI: 10.1016/j.canep.2024.102725] [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: 07/31/2024] [Revised: 11/16/2024] [Accepted: 12/03/2024] [Indexed: 12/23/2024]
Abstract
BACKGROUND High fasting plasma glucose (HFPG) has been indicated as one of the important risk factors for cancers. This study aimed to estimate the disease burden of cancers attributable to HFPG in China from 1990 to 2021 and predict the burden until 2031. METHODS The data of cancers attributable to HFPG were extracted from Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 project. A joinpoint regression model was conducted to estimate the temporal trends from 1990 to 2021. The effects of age, period, and cohort were estimated by an age-period-cohort (APC) model. Lastly, a Bayesian APC model was employed to predict the disease burden for the next decade. RESULTS From 1990-2021, cancer deaths attributable to HFPG in China increased by 232 % (95 % uncertainty interval [UI]: 156-330.77 %), and disability-adjusted life-years (DALYs) increased by 195.4 % (95 % UI: 127.38-289.7 %). In addition, the average annual percentage change (AAPC) for the age-standardized mortality rate (ASMR) and age-standardized DALYs rate (ASDR) were 0.6364 % (95 % confidence interval [CI]: 0.4234-0.8498 %) and 0.6263 % (95 % CI: 0.3024-0.9512 %), respectively. Among all cancer types, pancreatic cancer had the largest increase in disease burden. The risks of mortality and DALYs increased with age, while showing initial rapid increase with period growth followed by relative stabilization. The cohort effect indicates that males born later had higher risks of mortality and DALYs. Finally, despite a continuous decline in both ASMR and ASDR, the numbers of deaths and DALYs were projected to continue increasing in the next decade. CONCLUSIONS The disease burden of cancers attributable to HFPG significantly increased from 1990 to 2021 in China, and the numbers of deaths and DALYs would continuously increase in the next decade. Therefore, it is necessary to introduce targeted policies controlling the disease burden.
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Affiliation(s)
- Zhong Zheng
- College of Public Health, Zhengzhou University, Zhengzhou, Henan Province 450001, China; Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, Henan Province 450052, China
| | - Shaojie Xu
- Department of Nursing, the Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province 450052, China
| | - Jicun Zhu
- Department of Pharmacy, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province 450052, China
| | - Qian Yang
- Prenatal Diagnosis Center, The Third Affiliated Hospital of Zhengzhou University/Maternal and Child Health Hospital of Henan Province, Zhengzhou, Henan Province 450052, China
| | - Hua Ye
- College of Public Health, Zhengzhou University, Zhengzhou, Henan Province 450001, China; Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, Henan Province 450052, China
| | - Meng Li
- College of Public Health, Zhengzhou University, Zhengzhou, Henan Province 450001, China; Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, Henan Province 450052, China
| | - Xiaoyue Zhang
- College of Public Health, Zhengzhou University, Zhengzhou, Henan Province 450001, China; Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, Henan Province 450052, China
| | - Haiyan Liu
- College of Public Health, Zhengzhou University, Zhengzhou, Henan Province 450001, China; Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, Henan Province 450052, China
| | - Yifan Cheng
- College of Public Health, Zhengzhou University, Zhengzhou, Henan Province 450001, China; Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, Henan Province 450052, China
| | - Yuanlin Zou
- College of Public Health, Zhengzhou University, Zhengzhou, Henan Province 450001, China; Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, Henan Province 450052, China
| | - Yin Lu
- College of Public Health, Zhengzhou University, Zhengzhou, Henan Province 450001, China; Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, Henan Province 450052, China
| | - Peng Wang
- College of Public Health, Zhengzhou University, Zhengzhou, Henan Province 450001, China; Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, Henan Province 450052, China.
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Luo Y, Li CY, Wang YQ, Xiang SM, Zhao C. Diabetic ulcer with cutaneous squamous cell carcinoma: A case report. World J Clin Oncol 2024; 15:1514-1519. [PMID: 39720643 PMCID: PMC11514373 DOI: 10.5306/wjco.v15.i12.1514] [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: 07/27/2024] [Revised: 09/02/2024] [Accepted: 09/10/2024] [Indexed: 10/22/2024] Open
Abstract
BACKGROUND Chronic skin ulcers are a risk factor for the development of skin tumors. In patients with diabetes, chronic refractory ulcers may also contribute to higher susceptibility to skin tumors. Timely surgical removal of chronic and nonhealing diabetic foot ulcers can effectively prevent progression to squamous cell carcinoma. Such cases may be misdiagnosed owing to currently insufficient clinical evidence. However, in cases of chronic ulcer wounds, it is crucial to enhance clinical awareness regarding their potential progression into malignant lesions. CASE SUMMARY An 84-year-old male patient with diabetes presented with a significantly ulcerated area on his foot. The ulcer had been present to varying degrees since 1996. Between 2012 and July 2019, even after receiving treatments such as herbal medicines or heat clearance and detoxification complete healing of the wound was not achieved. In July 2020, histopathological analysis confirmed a well-differentiated cutaneous squamous cell carcinoma. After the treatments, the ulcer wound healed slowly and did not expand. CONCLUSION Potentially malignant lesions in chronic ulcer wounds should be identified and treated in a timely manner to prevent their progression.
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Affiliation(s)
- Yun Luo
- Department of Vascular Surgery in Traditional Chinese Medicine, Shanghai TCM-Integrated Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200082, China
| | - Chen-Ying Li
- Department of Traditional Chinese Medicine, Shanghai Yangpu District Xinjiangwancheng Community Healthcare Center, Shanghai 200438, China
| | - Yu-Qing Wang
- Department of Vascular Surgery in Traditional Chinese Medicine, Shanghai TCM-Integrated Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200082, China
| | - Sheng-Min Xiang
- Department of Vascular Surgery in Traditional Chinese Medicine, Shanghai TCM-Integrated Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200082, China
| | - Cheng Zhao
- Department of Vascular Surgery in Traditional Chinese Medicine, Shanghai TCM-Integrated Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200082, China
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Natalicchio A, Marrano N, Montagnani M, Gallo M, Faggiano A, Zatelli MC, Argentiero A, Del Re M, D'Oronzo S, Fogli S, Franchina T, Giuffrida D, Gori S, Ragni A, Marino G, Mazzilli R, Monami M, Morviducci L, Renzelli V, Russo A, Sciacca L, Tuveri E, Cortellini A, Di Maio M, Candido R, Perrone F, Aimaretti G, Avogaro A, Silvestris N, Giorgino F. Glycemic control and cancer outcomes in oncologic patients with diabetes: an Italian Association of Medical Oncology (AIOM), Italian Association of Medical Diabetologists (AMD), Italian Society of Diabetology (SID), Italian Society of Endocrinology (SIE), Italian Society of Pharmacology (SIF) multidisciplinary critical view. J Endocrinol Invest 2024; 47:2915-2928. [PMID: 38935200 PMCID: PMC11549129 DOI: 10.1007/s40618-024-02417-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/12/2024] [Accepted: 06/16/2024] [Indexed: 06/28/2024]
Abstract
BACKGROUND Increasing evidence suggests that diabetes increases the risk of developing different types of cancer. Hyperinsulinemia, hyperglycemia and chronic inflammation, characteristic of diabetes, could represent possible mechanisms involved in cancer development in diabetic patients. At the same time, cancer increases the risk of developing new-onset diabetes, mainly caused by the use of specific anticancer therapies. Of note, diabetes has been associated with a ∼10% increase in mortality for all cancers in comparison with subjects who did not have diabetes. Diabetes is associated with a worse prognosis in patients with cancer, and more recent findings suggest a key role for poor glycemic control in this regard. Nevertheless, the association between glycemic control and cancer outcomes in oncologic patients with diabetes remains unsettled and poorly debated. PURPOSE The current review seeks to summarize the available evidence on the effect of glycemic control on cancer outcomes, as well as on the possibility that timely treatment of hyperglycemia and improved glycemic control in patients with cancer and diabetes may favorably affect cancer outcomes.
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Affiliation(s)
- A Natalicchio
- Department of Precision and Regenerative Medicine and Ionian Area, Section of Internal Medicine, Endocrinology, Andrology and Metabolic Diseases, University of Bari Aldo Moro, Piazza Giulio Cesare, 11, I-70124, Bari, Italy
| | - N Marrano
- Department of Precision and Regenerative Medicine and Ionian Area, Section of Internal Medicine, Endocrinology, Andrology and Metabolic Diseases, University of Bari Aldo Moro, Piazza Giulio Cesare, 11, I-70124, Bari, Italy
| | - M Montagnani
- Department of Precision and Regenerative Medicine and Ionian Area, Section of Pharmacology, University of Bari Aldo Moro, Bari, Italy
| | - M Gallo
- Endocrinology and Metabolic Diseases Unit, Azienda Ospedaliero-Universitaria SS Antonio e Biagio e Cesare Arrigo of Alessandria, Alessandria, Italy
| | - A Faggiano
- Endocrinology Unit, Department of Clinical & Molecular Medicine, Sant'Andrea Hospital, Sapienza University of Rome, Rome, Italy
| | - M C Zatelli
- Section of Endocrinology, Geriatrics and Internal Medicine, Department of Medical Sciences, University of Ferrara, Ferrara, Italy
| | - A Argentiero
- Medical Oncology Unit, IRCCS Istituto Tumori "Giovanni Paolo II", Bari, Italy
| | - M Del Re
- Department of Clinical and Experimental Medicine, University of Pisa, 55, Via Roma, 56126, Pisa, Italy
| | - S D'Oronzo
- Interdisciplinary Department of Medicine, University of Bari Aldo Moro, Bari, Italy
| | - S Fogli
- Clinical Pharmacology and Pharmacogenetics Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - T Franchina
- Medical Oncology Unit, Department of Human Pathology "G. Barresi", University of Messina, Messina, Italy
| | - D Giuffrida
- Department of Oncology, Istituto Oncologico del Mediterraneo, Viagrande, Catania, Italy
| | - S Gori
- Oncologia Medica, IRCCS Don Calabria-Sacro Cuore Hospital, Negrar, Verona, Italy
| | - A Ragni
- Endocrinology and Metabolic Diseases Unit, Azienda Ospedaliero-Universitaria SS Antonio e Biagio e Cesare Arrigo of Alessandria, Alessandria, Italy
| | - G Marino
- Internal Medicine Department, Ospedale dei Castelli, Asl Roma 6, Ariccia, Rome, Italy
| | - R Mazzilli
- Endocrinology Unit, Department of Clinical & Molecular Medicine, Sant'Andrea Hospital, Sapienza University of Rome, Rome, Italy
| | - M Monami
- Diabetology, Careggi Hospital and University of Florence, Florence, Italy
| | - L Morviducci
- Diabetology and Nutrition Unit, Department of Medical Specialties, ASL Roma 1 - S. Spirito Hospital, Rome, Italy
| | - V Renzelli
- Diabetologist and Endocrinologist, Italian Association of Clinical Diabetologists, Rome, Italy
| | - A Russo
- Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy
| | - L Sciacca
- Department of Clinical and Experimental Medicine, Endocrinology Section, University of Catania, Catania, Italy
| | - E Tuveri
- Diabetology, Endocrinology and Metabolic Diseases Service, ASL-Sulcis, Carbonia, Italy
| | - A Cortellini
- Operative Research Unit of Medical Oncology, Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo, 200, 00128, Rome, Italy
- Department of Medicine and Surgery, Universitá Campus Bio-Medico di Roma, Via Alvaro del Portillo, 21, 00128, Rome, Italy
- Department of Surgery and Cancer, Hammersmith Hospital Campus, Imperial College London, London, UK
| | - M Di Maio
- Department of Oncology, University of Turin, AOU Città Della Salute e della Scienza di Torino, Turin, Italy
| | - R Candido
- Department of Medical Surgical and Health Sciences, University of Trieste, 34149, Trieste, Italy
| | - F Perrone
- Clinical Trials Unit, National Cancer Institute, Naples, Italy
| | - G Aimaretti
- Endocrinology, Department of Translational Medicine, Università del Piemonte Orientale, Novara, Italy
| | - A Avogaro
- Department of Medicine, Section of Diabetes and Metabolic Diseases, University of Padova, Padua, Italy
| | - N Silvestris
- Medical Oncology Unit, Department of Human Pathology "G. Barresi", University of Messina, Messina, Italy
| | - F Giorgino
- Department of Precision and Regenerative Medicine and Ionian Area, Section of Internal Medicine, Endocrinology, Andrology and Metabolic Diseases, University of Bari Aldo Moro, Piazza Giulio Cesare, 11, I-70124, Bari, Italy.
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Ghareghomi S, Arghavani P, Mahdavi M, Khatibi A, García-Jiménez C, Moosavi-Movahedi AA. Hyperglycemia-driven signaling bridges between diabetes and cancer. Biochem Pharmacol 2024; 229:116450. [PMID: 39059774 DOI: 10.1016/j.bcp.2024.116450] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2024] [Revised: 07/21/2024] [Accepted: 07/23/2024] [Indexed: 07/28/2024]
Abstract
Growing epidemiological evidence indicates an association between obesity, type 2 diabetes, and certain cancers, suggesting the existence of common underlying mechanisms in these diseases. Frequent hyperglycemias in type 2 diabetes promote pro-inflammatory responses and stimulate intracellular metabolic flux which rewires signaling pathways and influences the onset and advancement of different types of cancers. Here, we review the provocative impact of hyperglycemia on a subset of interconnected signalling pathways that regulate (i) cell growth and survival, (ii) metabolism adjustments, (iii) protein function modulation in response to nutrient availability (iv) and cell fate and proliferation and which are driven respectively by PI3K (Phosphoinositide 3-kinase), AMPK (AMP-activated protein kinase), O-GlcNAc (O-linked N-acetylglucosamine) and Wnt/β-catenin. Specifically, we will elaborate on their involvement in glucose metabolism, inflammation, and cell proliferation, highlighting their interplay in the pathogenesis of diabetes and cancer. Furthermore, the influence of antineoplastic and antidiabetic drugs on the unbridled cellular pathways will be examined. This review aims to inspire the next molecular studies to understand how type 2 diabetes may lead to certain cancers. This will contribute to personalized medicine and direct better prevention strategies.
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Affiliation(s)
- Somayyeh Ghareghomi
- Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran; Department of Biotechnology, Faculty of Biological Sciences, Alzahra University, Tehran, Iran
| | - Payam Arghavani
- Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran
| | - Majid Mahdavi
- Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran
| | - Ali Khatibi
- Department of Biotechnology, Faculty of Biological Sciences, Alzahra University, Tehran, Iran.
| | - Custodia García-Jiménez
- Department of Basic Health Sciences, Faculty of Health Sciences, University Rey Juan Carlos. Alcorcón, Madrid, Spain.
| | - Ali A Moosavi-Movahedi
- Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran; UNESCO Chair on Interdisciplinary Research in Diabetes, University of Tehran, Tehran, Iran.
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Waki Y, Nobeyama Y, Nakagawa H, Asahina A. High prevalence of dermatophytosis of the feet in acral melanoma of the foot. J Dermatol 2024; 51:1098-1103. [PMID: 38711284 DOI: 10.1111/1346-8138.17256] [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: 04/16/2024] [Indexed: 05/08/2024]
Abstract
The clinical characteristics and pathogenesis of acral melanoma of the foot (AMF) have not been sufficiently elucidated. Clinical or subclinical persistent inflammation of the feet is caused by dermatophytosis of the feet (DPF). Persistent inflammation is potentially associated with oncogenesis. Moreover, diabetes has been reported to be associated with the development of dermatophytosis and cancer. The present study aimed to elucidate the clinical association between DPF and AMF, with consideration of diabetes. The medical records of 114 Japanese patients were retrospectively examined and divided into an AMF group (n = 30) and a control group consisting of patients with foot diseases other than melanoma (n = 84). Microscopic DPF screening was performed on all patients who reported symptoms in the foot, with or without AMF. Patients underwent a microscopic test to detect the presence of dermatophytes, and the diagnosis of DPF was made based on a positive result. In the AMF group, 18 (60.0%) and eight (26.7%) patients had DPF and diabetes, respectively. Four patients (13.3%) had both DPF and diabetes. In the control group, 25 (29.8%) and 11 (13.1%) patients had DPF and diabetes, respectively. Five patients (6.0%) had both DPF and diabetes. Univariate analyses showed a significantly higher prevalence of DPF in the AMF group than in the control group (odds ratio, 3.540; p = 0.003, Pearson χ2 test). Furthermore, multivariate analyses of sex, body mass index, DPF, and diabetes revealed DPF as a significant factor associated with AMF (odds ratio, 4.285; p = 0.002, logistic regression analysis). The hyperkeratotic type of DPF was more frequently observed in patients with AMF than in control patients (odds ratio, 11.083; p < 0.001, Pearson χ2 test). In conclusion, the present study found a significantly higher prevalence of DPF, especially its hyperkeratotic type, in patients with AMF. DPF may be associated with AMF pathogenesis.
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Affiliation(s)
- Yuma Waki
- Department of Dermatology, The Jikei University School of Medicine, Tokyo, Japan
| | - Yoshimasa Nobeyama
- Department of Dermatology, The Jikei University School of Medicine, Tokyo, Japan
| | - Hidemi Nakagawa
- Department of Dermatology, The Jikei University School of Medicine, Tokyo, Japan
| | - Akihiko Asahina
- Department of Dermatology, The Jikei University School of Medicine, Tokyo, Japan
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Ayat P, Sawass Najjar D, Alkaissi H, Gill H, Otey J, AlFaraj M, McFarlane SI. Differential Effect of Hyperglycemia on the Odds of Cancer Among the Adult Population of the United States. Cureus 2024; 16:e63061. [PMID: 39050345 PMCID: PMC11268948 DOI: 10.7759/cureus.63061] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/24/2024] [Indexed: 07/27/2024] Open
Abstract
Objective Accumulating evidence indicates a relationship between diabetes and cancer risk, with obesity, insulin resistance, and hyperglycemia being implicated as the major underlying pathogenetic mechanisms of increased cancer risk among people with diabetes. We aim to assess the differential effect of dysglycemia (prediabetes and diabetes) on the strength of association (odds) of cancer amongst the adult US diabetic population. Material and methods We analyzed data from the 1997-2013 National Health Interview Survey (NHIS) dataset, which applies a multistage area probability sampling design. We used descriptive statistics and logistic regression analyses to test the strengths of the association between diabetes, prediabetes, and cancer before and after adjusting for major risk factors for cancer, including age and body mass index (BMI). Results A total of 722,532 individuals were surveyed, with a mean age of 47.18 ±0.3 years (±SEM) and a BMI of 26.9 ±0.01 kg/m2. Between 1997 and 2013, BMI increased from 26.0 to 27.4 kg/m2, the diabetes rate increased from 4.1% to 7.6%, and associated cancer rates increased from 6.6% to 9.0%. Body mass index was 27.1 vs. 26.8 kg/m2, P < 0.01, for those with and without cancer, respectively. The unadjusted odds ratio for cancer was 1.92 (1.78-2.08) (95% CI) and 2.20 (2.13-2.27) for prediabetes and diabetes, respectively. After adjusting for age, BMI, race, and cigarette smoking, the odds ratio for cancer was 1.12 (1.03-1.22), P < 0.01, and 1.15 (1.11-1.18), P <0.01, for prediabetes and diabetes, respectively. Conclusion Among US adults, the increasing rate of diabetes over the years was associated with an increased rate of cancer. Diabetes and prediabetes have a graduated effect on cancer risk. While obesity is generally implicated as an underlying pathophysiologic link between diabetes and cancer, our study showed a modest difference in BMI between those with and without cancer. In addition, the effect of diabetes and prediabetes on the odds of cancer persisted after adjusting for BMI. These data collectively suggest that hyperglycemia is an attractive pathophysiologic mechanism that may play a role in increasing the odds of cancer among diabetic and prediabetic populations. Our study is consistent with the accumulating evidence implicating hyperglycemia in the pathogenesis of cancer, where glucose is used in PET scanning to detect cancer (the Warburg effect), and the ketogenic diet appears to be useful in cancer management, enhancing the effect of chemotherapeutic agents.
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Affiliation(s)
- Parinaz Ayat
- Internal Medicine, State University of New York (SUNY) Downstate Health Science University, New York City, USA
| | - Diana Sawass Najjar
- Internal Medicine, State University of New York (SUNY) Downstate Health Science University, New York City, USA
| | - Hussam Alkaissi
- Internal Medicine, National Institutes of Health (NIH) National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Bethesda, USA
| | - Harjinder Gill
- Internal Medicine, State University of New York (SUNY) Downstate Health Science University, New York City, USA
| | - Jennifer Otey
- Medicine, State University of New York (SUNY) Downstate Health Science University, New York City, USA
| | - Marwa AlFaraj
- Integrative Medicine, State University of New York (SUNY) Downstate Health Science University, New York City, USA
| | - Samy I McFarlane
- Internal Medicine, Endocrine Division, State University of New York (SUNY) Downstate Health Science University, New York City, USA
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Cosmin Stan M, Paul D. Diabetes and Cancer: A Twisted Bond. Oncol Rev 2024; 18:1354549. [PMID: 38835644 PMCID: PMC11148650 DOI: 10.3389/or.2024.1354549] [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: 06/30/2023] [Accepted: 04/08/2024] [Indexed: 06/06/2024] Open
Abstract
This paper presents an overview of the interconnection between various factors related to both cancer and type 2 diabetes mellitus (T2DM). Hyperglycemia, hyperinsulinemia, chronic inflammation, and obesity are involved in the development and progression of both diseases but, strong evidence for a direct causal relationship between diabetes and cancer, is lacking. Several studies described a relationship between hyperglycemia and cancer at the cellular, tissular and organismic levels but at the same time recent Mendelian randomization studies proved a significant causal relationship only between hyperglycemia and breast cancer. On the other hand, the association between both hyperinsulinemia and obesity and several cancer types appears to be robust as demonstrated by Mendelian randomized studies. Metabolic alterations, including the Warburg effect and excessive glucose consumption by tumors, are discussed, highlighting the potential impact of dietary restrictions, such as fasting and low-carb diets, on tumor growth and inflammation. Recent data indicates that circulating branched-chain amino acids levels, may represent novel biomarkers that may contribute to both better diabetes control and early pancreatic cancer detection. Understanding the underlying mechanisms and shared risk factors between cancer and T2DM can provide valuable insights for cancer prevention, early detection, and management strategies.
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Affiliation(s)
- Mihai Cosmin Stan
- Emergency County Hospital Rm. Vâlcea, Râmnicu Vâlcea, Romania
- Medical Oncology Department, University of Medicine and Pharmacy of Craiova, Craiova, Romania
| | - Doru Paul
- Weill Cornell Medicine, New York, NY, United States
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Vernì F. Vitamin B6 and diabetes and its role in counteracting advanced glycation end products. VITAMINS AND HORMONES 2024; 125:401-438. [PMID: 38997171 DOI: 10.1016/bs.vh.2024.02.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/14/2024]
Abstract
Naturally occurring forms of vitamin B6 include six interconvertible water-soluble compounds: pyridoxine (PN), pyridoxal (PL), pyridoxamine (PM), and their respective monophosphorylated derivatives (PNP, PLP, and PMP). PLP is the catalytically active form which works as a cofactor in approximately 200 reactions that regulate the metabolism of glucose, lipids, amino acids, DNA, and neurotransmitters. Most of vitamers can counteract the formation of reactive oxygen species and the advanced glycation end-products (AGEs) which are toxic compounds that accumulate in diabetic patients due to prolonged hyperglycemia. Vitamin B6 levels have been inversely associate with diabetes, while vitamin B6 supplementation reduces diabetes onset and its vascular complications. The mechanisms at the basis of the relation between vitamin B6 and diabetes onset are still not completely clarified. In contrast more evidence indicates that vitamin B6 can protect from diabetes complications through its role as scavenger of AGEs. It has been demonstrated that in diabetes AGEs can destroy the functionality of macromolecules such as protein, lipids, and DNA, thus producing tissue damage that result in vascular diseases. AGEs can be in part also responsible for the increased cancer risk associated with diabetes. In this chapter the relationship between vitamin B6, diabetes and AGEs will be discussed by showing the acquired knowledge and questions that are still open.
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Affiliation(s)
- F Vernì
- Department of Biology and Biotechnology "Charles Darwin" Sapienza University of Rome, Rome, Italy.
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Attia SM, Albekairi NA, Alshamrani AA, Ahmad SF, Almutairi F, Attia MSM, Ansari MA, Bakheet SA, Harisa GI, Nadeem A. Dapagliflozin suppresses diabetes-induced oxidative DNA damage and hypermethylation in mouse somatic cells. MUTATION RESEARCH. GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS 2024; 896:503765. [PMID: 38821673 DOI: 10.1016/j.mrgentox.2024.503765] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/19/2024] [Revised: 05/06/2024] [Accepted: 05/07/2024] [Indexed: 06/02/2024]
Abstract
Diabetes mellitus is a complex metabolic disorder resulting from the interplay of environmental, genetic, and epigenetic factors that increase the risk of cancer development. However, it is unclear whether the increased cancer risk is due to poor glycemic control or the use of some antidiabetic medications. Therefore, we investigated the genetic and epigenetic changes in somatic cells in a mouse model of diabetes and studied whether multiple exposures to the antidiabetic medication dapagliflozin influence these changes. We also elucidated the mechanism(s) of these ameliorations. The micronucleus test and modified comet assay were used to investigate bone marrow DNA damage and methylation changes. These assays revealed that dapagliflozin is non-genotoxic in the tested regimen, and oxidative DNA damage and hypermethylation were significantly higher in diabetic mice. Spectrophotometry also evaluated oxidative DNA damage and global DNA methylation, revealing similar significant alterations induced by diabetes. Conversely, the dapagliflozin-treated diabetic animals significantly reduced these changes. The expression of some genes involved in DNA repair and DNA methylation was disrupted considerably in the somatic cells of diabetic animals. In contrast, dapagliflozin treatment significantly restored these disruptions and enhanced DNA repair. The simultaneous effects of decreased oxidative DNA damage and hypermethylation levels suggest that dapagliflozin can be used as a safe antidiabetic drug to reduce DNA damage and hypermethylation in diabetes, demonstrating its usefulness in patients with diabetes to control hyperglycemia and decrease the development of its subsequent complications.
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Affiliation(s)
- Sabry M Attia
- Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.
| | - Norah A Albekairi
- Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia
| | - Ali A Alshamrani
- Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia
| | - Sheikh F Ahmad
- Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia
| | - Faris Almutairi
- Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia
| | - Mohamed S M Attia
- Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia
| | - Mushtaq A Ansari
- Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia
| | - Saleh A Bakheet
- Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia
| | - Gamaleldin I Harisa
- Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia
| | - Ahmed Nadeem
- Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia
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Khalil MAM, Sadagah NM, Tan J, Syed FO, Chong VH, Al-Qurashi SH. Pros and cons of live kidney donation in prediabetics: A critical review and way forward. World J Transplant 2024; 14:89822. [PMID: 38576756 PMCID: PMC10989475 DOI: 10.5500/wjt.v14.i1.89822] [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: 11/13/2023] [Revised: 12/11/2023] [Accepted: 01/16/2024] [Indexed: 03/15/2024] Open
Abstract
There is shortage of organs, including kidneys, worldwide. Along with deceased kidney transplantation, there is a significant rise in live kidney donation. The prevalence of prediabetes (PD), including impaired fasting glucose and impaired glucose tolerance, is on the rise across the globe. Transplant teams frequently come across prediabetic kidney donors for evaluation. Prediabetics are at risk of diabetes, chronic kidney disease, cardiovascular events, stroke, neuropathy, retinopathy, dementia, depression and nonalcoholic liver disease along with increased risk of all-cause mortality. Unfortunately, most of the studies done in prediabetic kidney donors are retrospective in nature and have a short follow up period. There is lack of prospective long-term studies to know about the real risk of complications after donation. Furthermore, there are variations in recommendations from various guidelines across the globe for donations in prediabetics, leading to more confusion among clinicians. This increases the responsibility of transplant teams to take appropriate decisions in the best interest of both donors and recipients. This review focuses on pathophysiological changes of PD in kidneys, potential complications of PD, other risk factors for development of type 2 diabetes, a review of guidelines for kidney donation, the potential role of diabetes risk score and calculator in kidney donors and the way forward for the evaluation and selection of prediabetic kidney donors.
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Affiliation(s)
- Muhammad Abdul Mabood Khalil
- Center of Renal Diseases and Transplantation, King Fahad Armed Forces Hospital Jeddah, Jeddah 23311, Saudi Arabia
| | - Nihal Mohammed Sadagah
- Center of Renal Diseases and Transplantation, King Fahad Armed Forces Hospital Jeddah, Jeddah 23311, Saudi Arabia
| | - Jackson Tan
- Department of Nephrology, RIPAS Hospital Brunei Darussalam, Brunei Muara BA1710, Brunei Darussalam
| | - Furrukh Omair Syed
- Center of Renal Diseases and Transplantation, King Fahad Armed Forces Hospital Jeddah, Jeddah 23311, Saudi Arabia
| | - Vui Heng Chong
- Division of Gastroenterology and Hepatology, Department of Medicine, Raja Isteri Pengiran Anak Saleha Hospital, Bandar Seri Begawan BA1710, Brunei Darussalam
| | - Salem H Al-Qurashi
- Center of Renal Diseases and Transplantation, King Fahad Armed Forces Hospital Jeddah, Jeddah 23311, Saudi Arabia
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11
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Xu F, Jin J, Guo J, Xu F, Chen J, Liu Q, Song L, Zhang Z, Zhou L, Su J, Xiao C, Zhang Y, Yan M, He Q, Wu D, Chang C, Li X, Wu L. The clinical characteristics, gene mutations and outcomes of myelodysplastic syndromes with diabetes mellitus. J Cancer Res Clin Oncol 2024; 150:71. [PMID: 38305890 PMCID: PMC10837231 DOI: 10.1007/s00432-023-05591-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2023] [Accepted: 12/22/2023] [Indexed: 02/03/2024]
Abstract
PURPOSE Diabetes mellitus (DM) is the second most common comorbidity in myelodysplastic syndromes (MDS). The purpose of the study was to investigate the clinical characteristics of MDS patients with DM. METHODS A retrospective analysis was performed on the clinical data of 890 MDS patients with or without DM. Clinical data, including genetic changes, overall survival (OS), leukemia-free survival (LFS) and infection, were analyzed. RESULTS Among 890 patients, 184 (20.7%) had DM. TET2 and SF3B1 mutations occurred more frequently in the DM group than those in the non-DM group (p = 0.0092 and p = 0.0004, respectively). Besides, DM was an independent risk factor for infection (HR 2.135 CI 1.451-3.110, p = 0.000) in MDS. Compared to non-DM patients, MDS patients with DM had poor OS and LFS (p = 0.0002 and p = 0.0017, respectively), especially in the lower-risk group. While in multivariate analysis, DM did not retain its prognostic significance and the prognostic significance of infection was maintained (HR 2.488 CI 1.749-3.538, p = 0.000). CONCLUSIONS MDS patients with DM have an inferior prognosis which may due to higher infection incidence, with TET2 and SF3B1 mutations being more frequent in those cases.
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Affiliation(s)
- Fanhuan Xu
- Department of Hematology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China
| | - Jiacheng Jin
- Department of Hematology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China
| | - Juan Guo
- Department of Hematology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China
| | - Feng Xu
- Department of Hematology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China
| | - Jianan Chen
- Department of Hematology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China
| | - Qi Liu
- Department of Hematology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China
| | - Luxi Song
- Department of Hematology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China
| | - Zheng Zhang
- Department of Hematology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China
| | - Liyu Zhou
- Department of Hematology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China
- Department of Hematology, Shanghai Jiao Eighth People's Hospital, Shanghai, 200233, China
| | - Jiying Su
- Department of Hematology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China
| | - Chao Xiao
- Department of Hematology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China
| | - Yumei Zhang
- Department of Hematology, Shanghai Jiao Eighth People's Hospital, Shanghai, 200233, China
| | - Meng Yan
- Department of Hematology, Shanghai Jiao Eighth People's Hospital, Shanghai, 200233, China
| | - Qi He
- Department of Hematology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China
| | - Dong Wu
- Department of Hematology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China
| | - Chunkang Chang
- Department of Hematology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China.
| | - Xiao Li
- Department of Hematology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China.
| | - Lingyun Wu
- Department of Hematology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China.
- Department of Hematology, Shanghai Jiao Eighth People's Hospital, Shanghai, 200233, China.
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Gholami M. FTO is a major genetic link between breast cancer, obesity, and diabetes. Breast Cancer Res Treat 2024; 204:159-169. [PMID: 38071263 DOI: 10.1007/s10549-023-07188-4] [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: 07/08/2023] [Accepted: 10/26/2023] [Indexed: 01/24/2024]
Abstract
PURPOSE Breast cancer (BC), obesity, and type 2 diabetes mellitus (T2DM) are three complex diseases and health problems that are prevalent worldwide. The aim of this study was to investigate the common genetic associations between these diseases by referring back to the previous genome-wide association studies (GWAS). METHODS To this end, significant GWAS variants and common variants associated with BC, obesity, or diabetes were identified from the GWAS catalog. To perform candidate variants, the 1000-Genomes Project was used to find variants with linkage disequilibrium. Common variants between each category were identified (common candidate haplotypic variants). Finally, these variants and their associated genes were examined for SNP function analysis, gene expression, gene-gene correlation, and pathway analysis. RESULTS The results identified 7 variants associated with both T2DM and BC, 8 variants associated with both obesity and BC, and 167 variants associating obesity with T2DM. 91 variants and 4 haplotypic blocks such as CTC were identified on the FTO gene associated with obesity, BC, and T2DM. The results of TCGA data showed that FTO in gene expression was correlated with 6 other genes in the DNA repair pathway in BC subjects. CONCLUSIONS This study suggests that the FTO gene is one of the major genes shared by BC, T2DM, and obesity based on two DNA repair and inflammatory mechanisms. These results may provide a new perspective on the important role of the FTO gene and repair mechanism in the relationship between BC, obesity, and T2DM for future studies.
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Affiliation(s)
- Morteza Gholami
- Metabolic Disorders Research Center, Endocrinology and Metabolism Research Institute, North Kargar Ave, Tehran, Iran.
- Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
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13
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Biondi G, Marrano N, Borrelli A, Rella M, D’Oria R, Genchi VA, Caccioppoli C, Cignarelli A, Perrini S, Laviola L, Giorgino F, Natalicchio A. The p66 Shc Redox Protein and the Emerging Complications of Diabetes. Int J Mol Sci 2023; 25:108. [PMID: 38203279 PMCID: PMC10778847 DOI: 10.3390/ijms25010108] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2023] [Revised: 12/11/2023] [Accepted: 12/15/2023] [Indexed: 01/12/2024] Open
Abstract
Diabetes mellitus is a chronic metabolic disease, the prevalence of which is constantly increasing worldwide. It is often burdened by disabling comorbidities that reduce the quality and expectancy of life of the affected individuals. The traditional complications of diabetes are generally described as macrovascular complications (e.g., coronary heart disease, peripheral arterial disease, and stroke), and microvascular complications (e.g., diabetic kidney disease, retinopathy, and neuropathy). Recently, due to advances in diabetes management and the increased life expectancy of diabetic patients, a strong correlation between diabetes and other pathological conditions (such as liver diseases, cancer, neurodegenerative diseases, cognitive impairments, and sleep disorders) has emerged. Therefore, these comorbidities have been proposed as emerging complications of diabetes. P66Shc is a redox protein that plays a role in oxidative stress, apoptosis, glucose metabolism, and cellular aging. It can be regulated by various stressful stimuli typical of the diabetic milieu and is involved in various types of organ and tissue damage under diabetic conditions. Although its role in the pathogenesis of diabetes remains controversial, there is strong evidence regarding the involvement of p66Shc in the traditional complications of diabetes. In this review, we will summarize the evidence supporting the role of p66Shc in the pathogenesis of diabetes and its complications, focusing for the first time on the emerging complications of diabetes.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | | | - Francesco Giorgino
- Department of Precision and Regenerative Medicine and Ionian Area, Section of Internal Medicine, Endocrinology, Andrology and Metabolic Diseases, University of Bari Aldo Moro, 70124 Bari, Italy (M.R.); (R.D.); (V.A.G.)
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Zhao X, Shi W, Liu X, Zhang W. Emerging trends and research priorities in premature ovarian insufficiency genes: a bibliometric and visualization study. Gynecol Endocrinol 2023; 39:2283033. [PMID: 38010136 DOI: 10.1080/09513590.2023.2283033] [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: 07/31/2023] [Accepted: 11/07/2023] [Indexed: 11/29/2023] Open
Abstract
PURPOSE To illustrate the results achieved by genes in premature ovarian insufficiency (POI) and collaborations in the field, and to explore key themes and future directions. METHODS Articles and reviews related to POI genes published between 1990 and 2022 were retrieved from the Web of Science core collection (WoSCC) for the total bibliometric analysis. Tools were analyzed for publication, country, institution, journal, authors, reference, keywords, subject categories, funding agencies, and research hotspots using a bibliometric online analysis platform, Bibliographic Co-occurrence Matrix Builder (BICOMB), CiteSpace V, and VOSviewer. RESULTS A total of 2,232 papers were included in this study. Articles were published in 52 countries, with the United States publishing the most, followed by China. A total of 308 institutions contributed to relevant publications. Shandong University published the most papers. Qin Y's team published the most relevant papers. Human reproduction and fertility and sterility are the two journals with the most papers. X-chromosome abnormalities, transcription factor mutations, and FMR1 genes are the directions of more POI, and DNA repair is the keyword of the research frontier in recent years. CONCLUSIONS This study summarizes the relevant literature on POI gene research for the first time and analyzes the current hotspots and future trends in this field. The findings can further reveal the etiology, diagnosis, and treatment of POI, which is beneficial for researchers to grasp the genetic dynamics of POI women.
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Affiliation(s)
- Xi Zhao
- The First Affiliated Hospital of Hunan University of Traditional Chinese Medicine, Changsha, Hunan, P.R. China
| | - Wenying Shi
- The First Affiliated Hospital of Hunan University of Traditional Chinese Medicine, Changsha, Hunan, P.R. China
| | - Xiaojuan Liu
- The First Affiliated Hospital of Hunan University of Traditional Chinese Medicine, Changsha, Hunan, P.R. China
| | - Wei Zhang
- The First Affiliated Hospital of Hunan University of Traditional Chinese Medicine, Changsha, Hunan, P.R. China
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Ajiboye BO, Dada S, Fatoba HO, Lawal OE, Oyeniran OH, Adetuyi OY, Olatunde A, Taher M, Khotib J, Susanti D, Oyinloye BE. Dalbergiella welwitschia (Baker) Baker f. alkaloid-rich extracts attenuate liver damage in streptozotocin-induced diabetic rats. Biomed Pharmacother 2023; 168:115681. [PMID: 37837880 DOI: 10.1016/j.biopha.2023.115681] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2023] [Revised: 10/06/2023] [Accepted: 10/07/2023] [Indexed: 10/16/2023] Open
Abstract
This experiment was conducted to evaluate the Dalbergiella welwitschia alkaloid-rich extracts on liver damage in streptozotocin-induced diabetic rats. Hence, to induce diabetes, 45 mg/kg body weight of streptozotocin was intraperitoneally injected into the Wistar rats. Subsequently, 5 % (w/v) of glucose water was given to the induced animals for 24 h. Thus, the animals (48) were grouped into five groups (n = 8), containing normal control (NC), diabetic control (DC), diabetic rats placed on low (50 mg/kg body weight) and high (100 mg/kg body weight) doses of D. welwitschi alkaloid-rich leaf extracts (i.e. DWL and DWH respectively), and diabetic rats administered 200 mg/kg body weight of metformin (MET). The animals were sacrificed on the 21st day of the experiment, blood and liver were harvested, and different liver damage biomarkers were evaluated. The results obtained demonstrated that diabetic rats administered DWL, DWH and MET significantly (p < 0.05) increased hepatic AST, ALT, albumin, SOD, CAT, GSH, and GPX levels when compared to DC with no significant (p > 0.05) different when compared with NC. Also, diabetic rats administered DWL, DWH and MET revealed a significant (p < 0.05) decrease in GGT and MDA levels, as well as, fragmented DNA and protein carbonyl levels when compared to DC with no significant (p > 0.05) different when compared with NC. In addition, histological examination revealed that diabetic rats placed on DWL, DWH and MET normalized the hepatocytes. Consequently, it can be inferred that alkaloid-rich extracts from D. welwitschi leaf could be helpful in improving liver damage associated with diabetes mellitus rats.
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Affiliation(s)
- B O Ajiboye
- Phytomedicine and Molecular Toxicology Research Laboratory, Department of Biochemistry, Federal University Oye-Ekiti, Ekiti State, Nigeria; Institute of Drug Research and Development, SE Bogoro Center, Afe Babalola University, Ado-Ekiti, Nigeria.
| | - S Dada
- Phytomedicine, Biochemical Toxicology and Biotechnology Research Laboratories, Department of Biochemistry, College of Sciences, Afe Babalola University, Ado-Ekiti, Nigeria
| | - H O Fatoba
- Phytomedicine and Molecular Toxicology Research Laboratory, Department of Biochemistry, Federal University Oye-Ekiti, Ekiti State, Nigeria
| | - O E Lawal
- Phytomedicine and Molecular Toxicology Research Laboratory, Department of Biochemistry, Federal University Oye-Ekiti, Ekiti State, Nigeria
| | - O H Oyeniran
- Functional Foods, Nutraceuticals, and Phytomedicine Unit, Department of Biochemistry, Federal University Oye-Ekiti, Ekiti State, Nigeria
| | - O Y Adetuyi
- Phytomedicine and Molecular Toxicology Research Laboratory, Department of Biochemistry, Federal University Oye-Ekiti, Ekiti State, Nigeria
| | - A Olatunde
- Phytomedicine and Natural Products Drug Discovery, Department of Medical Biochemistry, Abubakar Tafawa Balewa University, Bauchi, Bauchi State, Nigeria
| | - M Taher
- Department of Pharmaceutical Technology, Kulliyyah of Pharmacy, International Islamic University Malaysia, 25200 Kuantan, Pahang, Malaysia; Pharmaceutics and Translational Research Group, Kulliyyah of Pharmacy, International Islamic University Malaysia, 25200 Kuantan, Pahang, Malaysia
| | - J Khotib
- Department of Pharmacy Practice, Faculty of Pharmacy, Airlangga University, 60115 Surabaya, Indonesia.
| | - D Susanti
- Department of Chemistry, Kulliyyah of Science, International Islamic University Malaysia, 25200 Kuantan, Pahang, Malaysia
| | - B E Oyinloye
- Institute of Drug Research and Development, SE Bogoro Center, Afe Babalola University, Ado-Ekiti, Nigeria; Phytomedicine, Biochemical Toxicology and Biotechnology Research Laboratories, Department of Biochemistry, College of Sciences, Afe Babalola University, Ado-Ekiti, Nigeria; Biotechnology and Structural Biology (BSB) Group, Department of Biochemistry and Microbiology, University of Zululand, South Africa
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Thongsroy J, Mutirangura A. The inverse association between DNA gaps and HbA1c levels in type 2 diabetes mellitus. Sci Rep 2023; 13:18987. [PMID: 37923892 PMCID: PMC10624909 DOI: 10.1038/s41598-023-46431-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2023] [Accepted: 10/31/2023] [Indexed: 11/06/2023] Open
Abstract
Naturally occurring DNA gaps have been observed in eukaryotic DNA, including DNA in nondividing cells. These DNA gaps are found less frequently in chronologically aging yeast, chemically induced senescence cells, naturally aged rats, D-galactose-induced aging model rats, and older people. These gaps function to protect DNA from damage, so we named them youth-associated genomic stabilization DNA gaps (youth-DNA-gaps). Type 2 diabetes mellitus (type 2 DM) is characterized by an early aging phenotype. Here, we explored the correlation between youth-DNA-gaps and the severity of type 2 DM. Here, we investigated youth-DNA-gaps in white blood cells from normal controls, pre-DM, and type 2 DM patients. We found significantly decreased youth-DNA-gap numbers in the type 2 DM patients compared to normal controls (P = 0.0377, P = 0.0018 adjusted age). In the type 2 DM group, youth-DNA-gaps correlate directly with HbA1c levels. (r = - 0.3027, P = 0.0023). Decreased youth-DNA-gap numbers were observed in patients with type 2 DM and associated with increased HbA1c levels. Therefore, the decrease in youth-DNA-gaps is associated with the molecular pathogenesis of high blood glucose levels. Furthermore, youth-DNA-gap number is another marker that could be used to determine the severity of type 2 DM.
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Affiliation(s)
- Jirapan Thongsroy
- School of Medicine, Walailak University, Nakhon Si Thammarat, 80160, Thailand.
- Research Center in Tropical Pathobiology, Walailak University, Nakhon Si Thammarat, 80160, Thailand.
| | - Apiwat Mutirangura
- Center for Excellence in Molecular Genetics of Cancer and Human Diseases, Chulalongkorn University, Bangkok, Thailand
- Department of Anatomy, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
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Elbahrawy A, Atalla H, Mahmoud AA, Eliwa A, Alsawak A, Alboraie M, Madian A, Alashker A, Mostafa S, Alwassief A, Aly HH. Prediction and surveillance of de novo HCC in patients with compensated advanced chronic liver disease after hepatitis C virus eradication with direct antiviral agents. FRONTIERS IN VIROLOGY 2023; 3. [DOI: 10.3389/fviro.2023.1227317] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
Abstract
The risk of hepatocellular carcinoma (HCC) diminishes in patients with hepatitis C virus (HCV)-related advanced chronic liver disease after virological cure. However, despite viral clearance, HCV-induced epigenetic alterations, immune dysregulations, and hepatic parenchymal injuries remain, contributing to de novo HCC occurrence. While HCC incidence is low (0.45 – 0.5%) in patients with advanced fibrosis (F3), the presence of liver cirrhosis and clinically significant portal hypertension increases the HCC risk. The cost-effectiveness of lifelong HCC surveillance in patients with compensated advanced chronic liver disease (cACLD) has sparked debate, raising questions about the most reliable noninvasive tests and stratification models for predicting HCC in patients with sustained virological response (SVR). Furthermore, identifying cACLD patients who may not require long-term HCC surveillance after SVR remains crucial. Several HCC risk stratification scores have been suggested for patients with cACLD, and emerging evidence supports individualized care based on personalized risk assessments. This review focuses on revising the pretreatment and posttreatment predictors of HCC, as well as the indications for HCC surveillance in cACLD patients treated with direct-acting antivirals.
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Wang Y, Liu H, Hu X, Wang A, Wang A, Kang S, Zhang L, Gu W, Dou J, Mu Y, Chen K, Wang W, Lyu Z. Association between hemoglobin glycation index and 5-year major adverse cardiovascular events: the REACTION cohort study. Chin Med J (Engl) 2023; 136:2468-2475. [PMID: 37265382 PMCID: PMC10586840 DOI: 10.1097/cm9.0000000000002717] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2022] [Indexed: 06/03/2023] Open
Abstract
BACKGROUND The hemoglobin glycation index (HGI) was developed to quantify glucose metabolism and individual differences and proved to be a robust measure of individual glycosylated hemoglobin (HbA1c) bias. Here, we aimed to explore the relationship between different HGIs and the risk of 5-year major adverse cardiovascular events (MACEs) by performing a large multicenter cohort study in China. METHODS A total of 9791 subjects from the Risk Evaluation of Cancers in Chinese Diabetic Individuals: a Longitudinal Study (the REACTION study) were divided into five subgroups (Q1-Q5) with the HGI quantiles (≤5th, >5th and ≤33.3th, >33.3th and ≤66.7th, >66.7th and ≤95th, and >95th percentile). A multivariate logistic regression model constructed by the restricted cubic spline method was used to evaluate the relationship between the HGI and the 5-year MACE risk. Subgroup analysis between the HGI and covariates were explored to detect differences among the five subgroups. RESULTS The total 5-year MACE rate in the nationwide cohort was 6.87% (673/9791). Restricted cubic spline analysis suggested a U-shaped correlation between the HGI values and MACE risk after adjustment for cardiovascular risk factors ( χ2 = 29.5, P <0.001). After adjustment for potential confounders, subjects with HGIs ≤-0.75 or >0.82 showed odds ratios (ORs) for MACE of 1.471 (95% confidence interval [CI], 1.027-2.069) and 2.222 (95% CI, 1.641-3.026) compared to subjects with HGIs of >-0.75 and ≤-0.20. In the subgroup with non-coronary heart disease, the risk of MACE was significantly higher in subjects with HGIs ≤-0.75 (OR, 1.540 [1.039-2.234]; P = 0.027) and >0.82 (OR, 2.022 [1.392-2.890]; P <0.001) compared to those with HGIs of ≤-0.75 or >0.82 after adjustment for potential confounders. CONCLUSIONS We found a U-shaped correlation between the HGI values and the risk of 5-year MACE. Both low and high HGIs were associated with an increased risk of MACE. Therefore, the HGI may predict the 5-year MACE risk.
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Affiliation(s)
- Yuhan Wang
- Department of Endocrinology, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
| | - Hongzhou Liu
- Department of Endocrinology, The Second Medical Center and National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing 100853, China
| | - Xiaodong Hu
- Department of Endocrinology, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
| | - Anping Wang
- Department of Endocrinology, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
| | - Anning Wang
- Department of Endocrinology, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
| | - Shaoyang Kang
- Department of Endocrinology, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
| | - Lingjing Zhang
- Department of Endocrinology, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
| | - Weijun Gu
- Department of Endocrinology, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
| | - Jingtao Dou
- Department of Endocrinology, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
| | - Yiming Mu
- Department of Endocrinology, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
| | - Kang Chen
- Department of Endocrinology, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
| | - Weiqing Wang
- Department of Endocrinology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Institute of Endocrine and Metabolic Diseases, Shanghai 200025, China
| | - Zhaohui Lyu
- Department of Endocrinology, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
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Scholten M, Halling A. Associations of heart failure to prevalence of haematologic- and solid malignancies in southern Sweden: A cross-sectional study. PLoS One 2023; 18:e0292853. [PMID: 37831639 PMCID: PMC10575512 DOI: 10.1371/journal.pone.0292853] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2023] [Accepted: 09/29/2023] [Indexed: 10/15/2023] Open
Abstract
BACKGROUND Heart failure (HF) and cancer are common diseases among the elderly population. Many chronic diseases, including diabetes mellitus (DM), share risk factors and increase the incidence of HF and cancer. The aim of this study was to investigate if there was an association between HF and the prevalence of haematologic- and solid malignancies. METHODS The study population was comprised of almost one million adults living in southern Sweden in 2015. All participants were divided into seven age groups from 20 and onwards, and 10 percentiles according to their socioeconomic status (SES). All data concerning diagnoses from each consultation in both primary- and secondary health care were collected during 18 months. The prevalence of haematologic and solid malignancies was measured separately for men and women, age groups, SES and multimorbidity levels. Multivariable logistic regression was used to determine the associations between HF and the probability of having haematologic- and solid malignancies in more complex models including stratifying variables. RESULTS People with HF had a higher prevalence of haematologic- and solid malignancies than the general population, but a lower prevalence of solid malignancies than the multimorbid population. The people with HF had an increased OR for haematologic malignancies, 1.69 (95% CI 1.51-1.90), and solid malignancies, OR 1.21 (95% CI 1.16-1.26), when adjusted for gender and age. In more complex multivariate models, multimorbidity explained the increased OR for haematologic- and solid malignancies in people with HF. Increasing socioeconomic deprivation was associated with a decreased risk for solid malignancies, with the lowest risk in the most socioeconomically deprived CNI-percentile. CONCLUSIONS HF was shown to be associated with malignancies, especially haematologic malignancies. Multimorbidity, however, was an even more important factor for both haematologic- and solid malignancies than HF in our study, but not socioeconomic deprivation. Further research on the interactions between the chronic conditions in people with HF is warranted to examine the strength of association between HF and malignancies.
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Affiliation(s)
- Mia Scholten
- Department of Clinical Sciences, Malmö, Lund University, Malmö, Sweden
| | - Anders Halling
- Department of Clinical Sciences, Malmö, Lund University, Malmö, Sweden
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20
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Scherübl H. [Type-2-diabetes and gastrointestinal cancer screening]. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2023; 61:683-689. [PMID: 35697066 DOI: 10.1055/a-1821-9108] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/09/2023]
Abstract
More than 8000000 Germans suffer from diabetes. People with type-2-diabetes (T2D) are at increased risk of gastrointestinal adenocarcinomas. They often develop cancer at younger age and their tumor-specific 5-year-survival is generally shorter. Cancer has become the leading cause of death of T2D-patients. Both chronic hyperglycemia and insulin resistance can stimulate gastrointestinal (GI) tumor growth. T2D can cause colorectal, pancreatic, hepatocellular, biliary and gastric cancer as well as esophageal adenocarcinoma. Both low-risk lifestyle and gastrointestinal cancer screening are effective and reduce GI cancer risk and GI cancer mortality of T2D-patients.
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Affiliation(s)
- Hans Scherübl
- Klinik für Innere Medizin; Gastroenterol., GI Onkol. u. Infektiol., Vivantes Klinikum Am Urban, Berlin, Germany
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21
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Mišík M, Staudinger M, Kundi M, Worel N, Nersesyan A, Ferk F, Dusinska M, Azqueta A, Møller P, Knasmueller S. Use of the Single Cell Gel Electrophoresis Assay for the Detection of DNA-protective Dietary Factors: Results of Human Intervention Studies. MUTATION RESEARCH. REVIEWS IN MUTATION RESEARCH 2023; 791:108458. [PMID: 37031732 DOI: 10.1016/j.mrrev.2023.108458] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/06/2022] [Revised: 03/14/2023] [Accepted: 04/06/2023] [Indexed: 04/11/2023]
Abstract
The single cell gel electrophoresis technique is based on the measurement of DNA migration in an electric field and enables to investigate via determination of DNA-damage the impact of foods and their constituents on the genetic stability. DNA-damage leads to adverse effects including cancer, neurodegenerative disorders and infertility. In the last 25 years approximately 90 human intervention trials have been published in which DNA-damage, formation of oxidized bases, alterations of the sensitivity towards reactive oxygen species and chemicals and of repair functions were investigated with this technique. In approximately 50% of the studies protective effects were observed. Pronounced protection was found with certain plant foods (spinach, kiwi fruits, onions), coffee, green tea, honey and olive oil. Also diets with increased contents of vegetables caused positive effects. Small amounts of certain phenolics (gallic acid, xanthohumol) prevented oxidative damage of DNA; with antioxidant vitamins and cholecalciferol protective effects were only detected after intake of doses that exceed the recommended daily uptake values. The evaluation of the quality of the studies showed that many have methodological shortcomings (lack of controls, no calibration of repair enzymes, inadequate control of the compliance and statistical analyses) which should be avoided in future investigations.
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Affiliation(s)
- Miroslav Mišík
- Center for Cancer Research, Medical University of Vienna, Borschkegasse 8a, A 1090 Vienna, Austria
| | - Marlen Staudinger
- Center for Cancer Research, Medical University of Vienna, Borschkegasse 8a, A 1090 Vienna, Austria
| | - Michael Kundi
- Center for Public Health, Department of Environmental Health, Medical University of Vienna, Vienna, Austria
| | - Nadine Worel
- Center for Cancer Research, Medical University of Vienna, Borschkegasse 8a, A 1090 Vienna, Austria
| | - Armen Nersesyan
- Center for Cancer Research, Medical University of Vienna, Borschkegasse 8a, A 1090 Vienna, Austria
| | - Franziska Ferk
- Center for Cancer Research, Medical University of Vienna, Borschkegasse 8a, A 1090 Vienna, Austria
| | - Maria Dusinska
- Health Effects Laboratory, Department of Environmental Chemistry, NILU-Norwegian Institute for Air Research, Instituttveien 18, 2002 Kjeller, Norway
| | - Amaya Azqueta
- Department of Pharmacology and Toxicology, University of Navarra, Pamplona, Spain
| | - Peter Møller
- Section of Environmental Health, Department of Public Health, University of Copenhagen, Denmark
| | - Siegfried Knasmueller
- Center for Cancer Research, Medical University of Vienna, Borschkegasse 8a, A 1090 Vienna, Austria.
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22
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Varun K, Zoltan K, Alba S, Manuel B, Elisabeth K, Dimitrios T, Jan B G, Maik B, Khurrum S, Berend I, Stephen H, Thomas F, Julia S, Peter N, Stefan K. Elevated markers of DNA damage and senescence are associated with the progression of albuminuria and restrictive lung disease in patients with type 2 diabetes. EBioMedicine 2023; 90:104516. [PMID: 36934657 PMCID: PMC10025008 DOI: 10.1016/j.ebiom.2023.104516] [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: 09/14/2022] [Revised: 02/09/2023] [Accepted: 02/22/2023] [Indexed: 03/19/2023] Open
Abstract
BACKGROUND This study was conducted to investigate the cascade involving DNA damage, senescence, and senescence-associated secretory phenotype (SASP) in experimental diabetes and in a four-year follow-up study in patients with pre-diabetes and type 2 diabetes. METHODS Kidney, lung, and liver were studied in 4 months diabetic db/db mice and age-matched controls for the presence of DNA damage and fibrosis. DNA damage (comet-tail-length and ɤH2Ax-positivity in white blood cells), urinary p21-excretion, and plasma IL-6 and TGF-β1 were determined from 115 healthy participants, 34 patients with pre-diabetes and 221 with type 2 diabetes. Urinary albumin-creatinine-ratio, lung function, and transient elastography of the liver were performed in a prospective follow-up study over 4 years. FINDINGS db/db mice showed an increased nuclear ɤH2AX signal in all tissues as compared to the background control. Markers for DNA damage, senescence, and SASP were increased in patients with diabetes. The presence of nephropathy, restrictive lung disease (RLD), and increased liver stiffness was in a cross-sectional design associated with increased markers for DNA damage, senescence, and SASP. The progression of nephropathy over 4 years was predicted by increased DNA damage, senescence, and SASP, while the progression of RLD was associated with increased DNA damage and IL-6 only. The progression of liver stiffness was not associated with any of these parameters. HbA1c was not predictive for progression. INTERPRETATION In db/db mice, the cascade of DNA damage is associated with diabetes-related complications. In patients with diabetes, the progression of complications in the kidney and lung is predicted by markers reflecting DNA damage, and senescence-triggered organ fibrosis. FUNDING This work was supported by the German Research Foundation (DFG) in the CRC 1118 and CRC 1158, by the GRK DIAMICOM, by the German Center for Diabetes Research (DZD e.V.), and by the Ministry of Science, Research and the Arts, Baden-Württemberg (Kompetenznetzwerk Präventivmedizin).
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Affiliation(s)
- Kumar Varun
- Department of Endocrinology, Diabetology and Clinical Chemistry (Internal Medicine I), University Hospital of Heidelberg, Heidelberg, Germany; German Center for Diabetes Research (DZD), München-Neuherberg, Germany; European Molecular Biology Laboratory, Advanced Light Microscopy Facility, Heidelberg, Germany
| | - Kender Zoltan
- Department of Endocrinology, Diabetology and Clinical Chemistry (Internal Medicine I), University Hospital of Heidelberg, Heidelberg, Germany; German Center for Diabetes Research (DZD), München-Neuherberg, Germany
| | - Sulaj Alba
- Department of Endocrinology, Diabetology and Clinical Chemistry (Internal Medicine I), University Hospital of Heidelberg, Heidelberg, Germany; German Center for Diabetes Research (DZD), München-Neuherberg, Germany
| | - Blume Manuel
- Department of Endocrinology, Diabetology and Clinical Chemistry (Internal Medicine I), University Hospital of Heidelberg, Heidelberg, Germany
| | - Kliemank Elisabeth
- Department of Endocrinology, Diabetology and Clinical Chemistry (Internal Medicine I), University Hospital of Heidelberg, Heidelberg, Germany; German Center for Diabetes Research (DZD), München-Neuherberg, Germany
| | - Tsilingiris Dimitrios
- Department of Endocrinology, Diabetology and Clinical Chemistry (Internal Medicine I), University Hospital of Heidelberg, Heidelberg, Germany; German Center for Diabetes Research (DZD), München-Neuherberg, Germany
| | - Groener Jan B
- Department of Endocrinology, Diabetology and Clinical Chemistry (Internal Medicine I), University Hospital of Heidelberg, Heidelberg, Germany; German Center for Diabetes Research (DZD), München-Neuherberg, Germany; Medicover Neuroendokrinologie, Munich, Germany
| | - Brune Maik
- Department of Endocrinology, Diabetology and Clinical Chemistry (Internal Medicine I), University Hospital of Heidelberg, Heidelberg, Germany
| | - Shahzad Khurrum
- Institute for Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University Hospital of Leipzig, Germany
| | - Isermann Berend
- Institute for Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University Hospital of Leipzig, Germany
| | - Herzig Stephen
- German Center for Diabetes Research (DZD), München-Neuherberg, Germany; Helmholtz Diabetes Center, Institute for Diabetes and Cancer, Helmholtz Center Munich, Germany; Joint Heidelberg-IDC Translational Diabetes Program, Internal Medicine I, Heidelberg University Hospital, Heidelberg, Germany
| | - Fleming Thomas
- Department of Endocrinology, Diabetology and Clinical Chemistry (Internal Medicine I), University Hospital of Heidelberg, Heidelberg, Germany; German Center for Diabetes Research (DZD), München-Neuherberg, Germany
| | - Szendroedi Julia
- Department of Endocrinology, Diabetology and Clinical Chemistry (Internal Medicine I), University Hospital of Heidelberg, Heidelberg, Germany; German Center for Diabetes Research (DZD), München-Neuherberg, Germany
| | - Nawroth Peter
- Department of Endocrinology, Diabetology and Clinical Chemistry (Internal Medicine I), University Hospital of Heidelberg, Heidelberg, Germany; German Center for Diabetes Research (DZD), München-Neuherberg, Germany; Joint Heidelberg-IDC Translational Diabetes Program, Internal Medicine I, Heidelberg University Hospital, Heidelberg, Germany
| | - Kopf Stefan
- Department of Endocrinology, Diabetology and Clinical Chemistry (Internal Medicine I), University Hospital of Heidelberg, Heidelberg, Germany; German Center for Diabetes Research (DZD), München-Neuherberg, Germany.
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23
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Sohn J, Lee SE, Shim EY. DNA Damage and Repair in Eye Diseases. Int J Mol Sci 2023; 24:3916. [PMID: 36835325 PMCID: PMC9964121 DOI: 10.3390/ijms24043916] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2022] [Revised: 01/30/2023] [Accepted: 02/02/2023] [Indexed: 02/17/2023] Open
Abstract
Vision is vital for daily activities, and yet the most common eye diseases-cataracts, DR, ARMD, and glaucoma-lead to blindness in aging eyes. Cataract surgery is one of the most frequently performed surgeries, and the outcome is typically excellent if there is no concomitant pathology present in the visual pathway. In contrast, patients with DR, ARMD and glaucoma often develop significant visual impairment. These often-multifactorial eye problems can have genetic and hereditary components, with recent data supporting the role of DNA damage and repair as significant pathogenic factors. In this article, we discuss the role of DNA damage and the repair deficit in the development of DR, ARMD and glaucoma.
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Affiliation(s)
- Joanna Sohn
- Department of Molecular Medicine, The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA
- Keystone School, 119 E. Craig Pl., San Antonio, TX 78212, USA
| | - Sang-Eun Lee
- Department of Molecular Medicine, The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA
| | - Eun-Yong Shim
- Department of Molecular Medicine, The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA
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24
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Sun D, Chen S, Li S, Wang N, Zhang S, Xu L, Zhu S, Li H, Gu Q, Xu X, Wei F. Enhancement of glycolysis-dependent DNA repair regulated by FOXO1 knockdown via PFKFB3 attenuates hyperglycemia-induced endothelial oxidative stress injury. Redox Biol 2022; 59:102589. [PMID: 36577299 PMCID: PMC9803794 DOI: 10.1016/j.redox.2022.102589] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2022] [Revised: 12/14/2022] [Accepted: 12/23/2022] [Indexed: 12/26/2022] Open
Abstract
The accumulation of DNA damage induced by oxidative stress is a crucial pathogenic factor of endothelial loss in diabetic vascular complications, but it is still unknown whether aberrant glucose metabolism leads to defective DNA repair and accounts for hyperglycemia-induced endothelial oxidative stress injury. Here, we showed that Foxo1 knockdown alleviated diabetes-associated retinal DNA damage and vascular dysfunction. Mechanistically, FOXO1 knockdown avoided persistent DNA damage and cellular senescence under high glucose in endothelial cells by promoting DNA repair mediated by the MRN (MRE11-RAD50-NBS1 complex)-ATM pathway in response to oxidative stress injury. Moreover, FOXO1 knockdown mediated robust DNA repair by restoring glycolysis capacity under high glucose. During this process, the key glycolytic enzyme PFKFB3 was stimulated and, in addition to its promoting effect on glycolysis, directly participated in DNA repair. Under genotoxic stress, PFKFB3 relocated into oxidative stress-induced DNA damage sites and promoted DNA repair by interaction with the MRN-ATM pathway. Our study proposed that defective glycolysis-dependent DNA repair is present in diabetic endothelial cells and contributes to hyperglycemia-induced vascular dysfunction, which could provide novel therapeutic targets for diabetic vascular complications.
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Affiliation(s)
- Dandan Sun
- Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, China,National Clinical Research Center for Eye Diseases, Shanghai Key Laboratory of Ocular Fundus Disease, Shanghai Engineering Center for Visual Science and Photo Medicine, Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai, 200080, China
| | - Shimei Chen
- Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, China,National Clinical Research Center for Eye Diseases, Shanghai Key Laboratory of Ocular Fundus Disease, Shanghai Engineering Center for Visual Science and Photo Medicine, Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai, 200080, China
| | - Shenping Li
- Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, China,National Clinical Research Center for Eye Diseases, Shanghai Key Laboratory of Ocular Fundus Disease, Shanghai Engineering Center for Visual Science and Photo Medicine, Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai, 200080, China
| | - Ning Wang
- Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, China,National Clinical Research Center for Eye Diseases, Shanghai Key Laboratory of Ocular Fundus Disease, Shanghai Engineering Center for Visual Science and Photo Medicine, Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai, 200080, China
| | - Shuchang Zhang
- Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, China,National Clinical Research Center for Eye Diseases, Shanghai Key Laboratory of Ocular Fundus Disease, Shanghai Engineering Center for Visual Science and Photo Medicine, Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai, 200080, China
| | - Li Xu
- Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, China,National Clinical Research Center for Eye Diseases, Shanghai Key Laboratory of Ocular Fundus Disease, Shanghai Engineering Center for Visual Science and Photo Medicine, Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai, 200080, China
| | - Shaopin Zhu
- Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, China,National Clinical Research Center for Eye Diseases, Shanghai Key Laboratory of Ocular Fundus Disease, Shanghai Engineering Center for Visual Science and Photo Medicine, Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai, 200080, China
| | - Huiming Li
- Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, China
| | - Qing Gu
- Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, China,National Clinical Research Center for Eye Diseases, Shanghai Key Laboratory of Ocular Fundus Disease, Shanghai Engineering Center for Visual Science and Photo Medicine, Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai, 200080, China
| | - Xun Xu
- Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, China; National Clinical Research Center for Eye Diseases, Shanghai Key Laboratory of Ocular Fundus Disease, Shanghai Engineering Center for Visual Science and Photo Medicine, Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai, 200080, China.
| | - Fang Wei
- Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, China; National Clinical Research Center for Eye Diseases, Shanghai Key Laboratory of Ocular Fundus Disease, Shanghai Engineering Center for Visual Science and Photo Medicine, Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai, 200080, China.
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25
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Hong X, Hu Y, Yuan Z, Fang Z, Zhang X, Yuan Y, Guo C. Oxidatively Damaged Nucleic Acid: Linking Diabetes and Cancer. Antioxid Redox Signal 2022; 37:1153-1167. [PMID: 35946074 DOI: 10.1089/ars.2022.0096] [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] [Indexed: 11/13/2022]
Abstract
Significance: Our current knowledge of the mechanism between diabetes and cancer is limited. Oxidatively damaged nucleic acid is considered a critical factor to explore the connections between these two diseases. Recent Advances: The link between diabetes mellitus and cancer has attracted increasing attention in recent years. Emerging evidence supports that oxidatively damaged nucleic acid caused by an imbalance between reactive oxygen species generation and elimination is a bridge connecting diabetes and cancer. 8-Oxo-7,8-dihydro-2'-deoxyguanosine and 8-oxo-7,8-dihydroguanosine assume important roles as biomarkers in assessing the relationship between oxidatively damaged nucleic acid and cancer. Critical Issues: The consequences of diabetes are extensive and may lead to the occurrence of cancer by influencing a combination of factors. At present, there is no direct evidence that diabetes causes cancer by affecting a single factor. Furthermore, the difficulty in controlling variables and differences in detection methods lead to poor reliability and repeatability of results, and there are no clear cutoff values for biomarkers to indicate cancer risk. Future Directions: A better understanding of connections as well as mechanisms between diabetes and cancer is still needed. Both diabetes and cancer are currently intractable diseases. Further exploration of the specific mechanism of oxidatively damaged nucleic acid in the connection between diabetes and cancer is urgently needed. In the future, it is necessary to further take oxidatively damaged nucleic acid as an entry point to provide new ideas for the diagnosis and treatment of diabetes and cancer. Experimental drugs targeting the repair process of oxidatively generated damage require an extensive preclinical evaluation and could ultimately provide new treatment strategies for these diseases. Antioxid. Redox Signal. 37, 1153-1167.
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Affiliation(s)
- Xiujuan Hong
- Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, Ministry of Education), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Yiqiu Hu
- Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, Ministry of Education), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Zhijun Yuan
- Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, Ministry of Education), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Zhihao Fang
- Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, Ministry of Education), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Xiaoxiao Zhang
- Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, Ministry of Education), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Ying Yuan
- Department of Medical Oncology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Cancer Center, Zhejiang University, Hangzhou, China
| | - Cheng Guo
- Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, Ministry of Education), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Cancer Center, Zhejiang University, Hangzhou, China
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26
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Mukherjee AG, Wanjari UR, Gopalakrishnan AV, Bradu P, Sukumar A, Patil M, Renu K, Dey A, Vellingiri B, George A, Ganesan R. Implications of cancer stem cells in diabetes and pancreatic cancer. Life Sci 2022; 312:121211. [PMID: 36414089 DOI: 10.1016/j.lfs.2022.121211] [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: 08/23/2022] [Revised: 11/15/2022] [Accepted: 11/16/2022] [Indexed: 11/21/2022]
Abstract
This review provides a detailed study of pancreatic cancer (PC) and the implication of different types of cancers concerning diabetes. The combination of anti-diabetic drugs with other anti-cancer drugs and phytochemicals can help prevent and treat this disease. PC cancer stem cells (CSCs) and how they migrate and develop into malignant tumors are discussed. A detailed explanation of the different mechanisms of diabetes development, which can enhance the pancreatic CSCs' proliferation by increasing the IGF factor levels, epigenetic modifications, DNA damage, and the influence of lifestyle factors like obesity, and inflammation, has been discussed. It also explains how cancer due to diabetes is associated with high mortality rates. One of the well-known diabetic drugs, metformin, can be combined with other anti-cancer drugs and prevent the development of PC and has been taken as one of the prime focus in this review. Overall, this paper provides insight into the relationship between diabetes and PC and the methods that can be employed to diagnose this disease at an earlier stage successfully.
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Affiliation(s)
- Anirban Goutam Mukherjee
- Department of Biomedical Sciences, School of Bio-Sciences and Technology, Vellore Institute of Technology (VIT), Vellore, Tamil Nadu, 632014, India
| | - Uddesh Ramesh Wanjari
- Department of Biomedical Sciences, School of Bio-Sciences and Technology, Vellore Institute of Technology (VIT), Vellore, Tamil Nadu, 632014, India
| | - Abilash Valsala Gopalakrishnan
- Department of Biomedical Sciences, School of Bio-Sciences and Technology, Vellore Institute of Technology (VIT), Vellore, Tamil Nadu, 632014, India.
| | - Pragya Bradu
- Department of Biomedical Sciences, School of Bio-Sciences and Technology, Vellore Institute of Technology (VIT), Vellore, Tamil Nadu, 632014, India
| | - Aarthi Sukumar
- Department of Integrative Biology, School of Bio-Sciences and Technology, Vellore Institute of Technology, Vellore, Tamil Nadu, 632014, India
| | - Megha Patil
- Department of Biomedical Sciences, School of Bio-Sciences and Technology, Vellore Institute of Technology (VIT), Vellore, Tamil Nadu, 632014, India
| | - Kaviyarasi Renu
- Centre of Molecular Medicine and Diagnostics (COMManD), Department of Biochemistry, Saveetha Dental College & Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, 600077, Tamil Nadu, India
| | - Abhijit Dey
- Department of Life Sciences, Presidency University, Kolkata, West Bengal, 700073, India
| | - Balachandar Vellingiri
- Stem cell and Regenerative Medicine/Translational Research, Department of Zoology, School of Basic Sciences, Central University of Punjab (CUPB), Bathinda - 151401, Punjab, India
| | - Alex George
- Jubilee Centre for Medical Research, Jubilee Mission Medical College and Research Institute, Thrissur, 680005, Kerala, India
| | - Raja Ganesan
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon, 24252, Republic of Korea
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27
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Dobrică EC, Banciu ML, Kipkorir V, Khazeei Tabari MA, Cox MJ, Simhachalam Kutikuppala LV, Găman MA. Diabetes and skin cancers: Risk factors, molecular mechanisms and impact on prognosis. World J Clin Cases 2022; 10:11214-11225. [PMID: 36387789 PMCID: PMC9649529 DOI: 10.12998/wjcc.v10.i31.11214] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/16/2022] [Revised: 08/20/2022] [Accepted: 09/21/2022] [Indexed: 02/05/2023] Open
Abstract
Diabetes and skin cancers have emerged as threats to public health worldwide. However, their association has been less intensively studied. In this narrative review, we explore the common risk factors, molecular mechanisms, and prognosis of the association between cutaneous malignancies and diabetes. Hyperglycemia, oxidative stress, low-grade chronic inflammation, genetic, lifestyle, and environmental factors partially explain the crosstalk between skin cancers and this metabolic disorder. In addition, diabetes and its related complications may interfere with the appropriate management of cutaneous malignancies. Antidiabetic medication seems to exert an antineoplastic effect, however, future large, observation studies with a prospective design are needed to clarify its impact on the risk of malignancy in diabetes. Screening for diabetes in skin cancers, as well as close follow-up for the development of cutaneous malignancies in subjects suffering from diabetes, is warranted.
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Affiliation(s)
- Elena-Codruta Dobrică
- Doctoral School, University of Medicine and Pharmacy of Craiova, Craiova 200349, Romania
| | - Madalina Laura Banciu
- Department of Dermatology, "Elias" University Emergency Hospital, Bucharest 011461, Romania
| | - Vincent Kipkorir
- Department of Human Anatomy, University of Nairobi, College of Health Sciences, Nairobi 00100, Kenya
| | | | - Madeleine Jemima Cox
- University of New South Wales, University of New South Wales, Sydney 2052, Australia
| | | | - Mihnea-Alexandru Găman
- Faculty of Medicine, "Carol Davila" University of Medicine and Pharmacy, Bucharest 050474, Romania
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28
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Hattori N, Ikeda H, Watanabe T, Satta Y, Ehira T, Suzuki T, Kiyokawa H, Nakahara K, Takahashi H, Matsunaga K, Matsumoto N, Yasuda H, Suzuki M, Itoh F, Tateishi K. Risk factors for liver-related mortality of patients with hepatitis C virus after sustained virologic response to direct-acting antiviral agents. JGH Open 2022; 6:685-691. [PMID: 36262540 PMCID: PMC9575322 DOI: 10.1002/jgh3.12805] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2022] [Revised: 07/01/2022] [Accepted: 07/27/2022] [Indexed: 06/16/2023]
Abstract
BACKGROUND AND AIM The aim of this study was to identify the factors associated with liver-related and non-liver-related mortality of patients with hepatitis C virus (HCV) after sustained virologic response (SVR) to direct-acting antiviral agents (DAAs). METHODS We conducted a retrospective, single-center cohort study of HCV patients cured by DAAs. RESULTS A total of 330 patients with SVR to DAAs were eligible. The median follow-up period was 3.38 years (inter-quartile range: 2.03-4.58). The cumulative liver-related or non-liver-related mortality rates at 1, 3, and 5 years were 0.00 or 1.29%, 2.87 or 3.60%, and 5.10 or 9.46, respectively. Among the liver-related deaths, 9 of the 10 were from liver cancer. Among the non-liver-related deaths, the most common cause was malignancy. Through multivariate analysis using the Cox proportional hazard model, diabetes mellitus (DM, hazard ratio 13.1, 95% confidence interval 2.81-61.3) and a history of hepatocellular carcinoma (HCC, 12.8, 2.76-59.2), independently predicted liver-related death. No variables were associated with non-liver-related death. CONCLUSION Our findings suggest that DM and a history of HCC are risk factors for liver-related mortality of HCV patients cured by DAAs. These results indicate that early management of HCV and HCC surveillance of diabetic patients after SVR are important to increase the chance of survival. Further studies are needed to confirm the association of DM and HCC history with survival.
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Affiliation(s)
- Nobuhiro Hattori
- Department of Internal Medicine, Division of Gastroenterology and HepatologySt. Marianna University School of MedicineKawasakiJapan
| | - Hiroki Ikeda
- Department of Internal Medicine, Division of Gastroenterology and HepatologySt. Marianna University School of MedicineKawasakiJapan
| | - Tsunamasa Watanabe
- Department of Internal Medicine, Division of Gastroenterology and HepatologySt. Marianna University School of MedicineKawasakiJapan
| | - Yosuke Satta
- Department of Internal Medicine, Division of Gastroenterology and HepatologySt. Marianna University School of MedicineKawasakiJapan
| | - Takuya Ehira
- Department of Internal Medicine, Division of Gastroenterology and HepatologySt. Marianna University School of MedicineKawasakiJapan
| | - Tatsuya Suzuki
- Department of Internal Medicine, Division of Gastroenterology and HepatologySt. Marianna University School of MedicineKawasakiJapan
| | - Hirofumi Kiyokawa
- Department of Internal Medicine, Division of Gastroenterology and HepatologySt. Marianna University School of MedicineKawasakiJapan
| | - Kazunari Nakahara
- Department of Internal Medicine, Division of Gastroenterology and HepatologySt. Marianna University School of MedicineKawasakiJapan
| | - Hideaki Takahashi
- Division of Gastroenterology and HepatologySt. Marianna University Yokohama Seibu HospitalYokohamaJapan
| | - Kotaro Matsunaga
- Division of Gastroenterology and HepatologyKawasaki Municipal Tama HospitalKawasakiJapan
| | - Nobuyuki Matsumoto
- Division of Gastroenterology and HepatologySt. Marianna University Yokohama Seibu HospitalYokohamaJapan
| | - Hiroshi Yasuda
- Department of Internal Medicine, Division of Gastroenterology and HepatologySt. Marianna University School of MedicineKawasakiJapan
| | - Michihiro Suzuki
- Division of Gastroenterology and HepatologyKawasaki Municipal Tama HospitalKawasakiJapan
| | - Fumio Itoh
- Department of Internal Medicine, Division of Gastroenterology and HepatologySt. Marianna University School of MedicineKawasakiJapan
| | - Keisuke Tateishi
- Department of Internal Medicine, Division of Gastroenterology and HepatologySt. Marianna University School of MedicineKawasakiJapan
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Shi F, Xu Y, Zhang S, Fu Z, Yu Q, Zhang S, Sun M, Zhao X, Feng X. Decabromodiphenyl ethane affects embryonic development by interfering with nuclear F-actin in zygotes and leads to cognitive and social disorders in offspring mice. FASEB J 2022; 36:e22445. [PMID: 35816173 DOI: 10.1096/fj.202200586r] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2022] [Revised: 06/07/2022] [Accepted: 06/27/2022] [Indexed: 12/12/2022]
Abstract
Decabromodiphenyl ethane (DBDPE) is a novel retardant. DBDPE is used in various flammable consumer products such as electronics, building materials, textiles, and children's toys. The presence of DBDPE in humans makes it extremely urgent to assess the health effects of DBDPE exposure. Here, we used female mice as an animal model to investigate the effects of DBDPE on embryonic development and offspring health. The results showed that 50 μg/kg bw/day of DBDPE exposure did not affect spindle rotation in oocytes after fertilization, but led to a decrease of pronuclei (PN) in zygotes. Further investigation found that DBDPE interferes with the self-assembly of F-actin in PN, resulting in PN reduction, DNA damage, and reduced expression of zygotic genome activating genes, and finally leading to abnormal embryonic development. More importantly, we found that maternal DBDPE exposure did not affect the growth and development of the first generation of offspring (F1) mice, but resulted in behavioral defects in F1 mice. Female F1 mice from DBDPE-exposed mothers exhibited increased motor activity and deficits in social behavior. Both female and male F1 mice from DBDPE-exposed mothers exhibited cognitive memory impairment. These results suggest that DBDPE has developmental toxicity on embryos and has a cross-generational interference effect. It is suggested that people should pay attention to the reproductive toxicity of DBDPE. In addition, it also provides a reference for studying the origin of neurological diseases and indicates that adult diseases caused by environmental pollutants may have begun in the embryonic stage.
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Affiliation(s)
- Feifei Shi
- College of Life Science, State Key Laboratory of Medicinal Chemical Biology, The Key Laboratory of Bioactive Materials, Ministry of Education, Nankai University, Tianjin, China
| | - Yixin Xu
- College of Life Science, State Key Laboratory of Medicinal Chemical Biology, The Key Laboratory of Bioactive Materials, Ministry of Education, Nankai University, Tianjin, China
| | - Shuhui Zhang
- College of Life Science, State Key Laboratory of Medicinal Chemical Biology, The Key Laboratory of Bioactive Materials, Ministry of Education, Nankai University, Tianjin, China
| | - Zhenhua Fu
- The Institute of Robotics and Automatic Information Systems, Nankai University, Tianjin, China
| | - Qian Yu
- College of Life Science, State Key Laboratory of Medicinal Chemical Biology, The Key Laboratory of Bioactive Materials, Ministry of Education, Nankai University, Tianjin, China
| | - Shaozhi Zhang
- College of Life Science, State Key Laboratory of Medicinal Chemical Biology, The Key Laboratory of Bioactive Materials, Ministry of Education, Nankai University, Tianjin, China
| | - Mingzhu Sun
- The Institute of Robotics and Automatic Information Systems, Nankai University, Tianjin, China
| | - Xin Zhao
- The Institute of Robotics and Automatic Information Systems, Nankai University, Tianjin, China
| | - Xizeng Feng
- College of Life Science, State Key Laboratory of Medicinal Chemical Biology, The Key Laboratory of Bioactive Materials, Ministry of Education, Nankai University, Tianjin, China
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The Impact of the Association between Cancer and Diabetes Mellitus on Mortality. J Pers Med 2022; 12:jpm12071099. [PMID: 35887596 PMCID: PMC9322980 DOI: 10.3390/jpm12071099] [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: 06/14/2022] [Revised: 06/29/2022] [Accepted: 06/30/2022] [Indexed: 11/17/2022] Open
Abstract
The prevalence of cancer, diabetes mellitus (DM), and hypertension is increasing in ageing populations. We analyzed the association of DM with cancer and its effects on cancer mortality. The data of 2009–2018 from the Korea National Hospital Discharge In-depth Injury Survey were used; 169,959 adults with cancer as the main diagnosis were identified. The association rule for unsupervised machine learning was used. Association rule mining was used to analyze the association between the diseases. Logistic regression was performed to determine the effects of DM on cancer mortality. DM prevalence was 12.9%. Cancers with high DM prevalence were pancreatic (29.9%), bile duct (22.7%), liver (21.4%), gallbladder (15.5%), and lung cancers (15.4%). Cancers with high hypertension prevalence were bile duct (31.4%), ureter (30.5%), kidney (29.5%), pancreatic (28.1%), and bladder cancers (27.5%). The bidirectional association between DM and hypertension in cancer was the strongest (lift = 2.629, interest support [IS] scale = 0.426), followed by that between lung cancer and hypertension (lift = 1.280, IS scale = 0.204), liver cancer and DM (lift = 1.658, IS scale = 0.204), hypertension and liver cancer and DM (lift = 3.363, IS scale = 0.197), colorectal cancer and hypertension (lift = 1.133, IS scale = 0.180), and gastric cancer and hypertension (lift = 1.072, IS scale = 0.175). DM increased liver cancer mortality (p = 0.000), while hypertension significantly increased the mortality rate of stomach, colorectal, liver, and lung cancers. Our study confirmed the association between cancer and DM. Consequently, a patient management strategy with presumptive diagnostic ability for DM and hypertension is required to decrease cancer mortality rates.
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Scherübl H. Krebsrisiko bei Prädiabetes und Typ-2-Diabetes mellitus. DIABETOL STOFFWECHS 2022. [DOI: 10.1055/a-1837-2035] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
ZusammenfassungKrebs ist nun die führende Todesursache bei Typ-2-Diabetes mellitus (T2D). Prädiabetes und T2D erhöhen das Risiko für bestimmte Tumoren. Zu den Prädiabetes- bzw. T2D-assoziierten Malignomen zählen gastrointestinale, gynäkologische, urologische und endokrine Karzinome aber auch Leukämien. Prädiabetes und T2D bedingen eine 1,2- bis 2,7-fach erhöhte Krebssterblichkeit. Zugrundeliegende Mechanismen der Assoziation zwischen T2D und Krebs beinhalten die chronische Hyperglykämie, einen chronischen systemischen Entzündungszustand, oxidativen Stress, Dyslipidämie, die Insulinresistenz sowie chronisch erhöhte Spiegel von insulin-like growth factor 1 (IGF-1) und von Insulin. Eine dauerhafte Gewichtsreduktion kann das Krebsrisiko adipöser T2D-Patienten signifikant senken. Ein gesunder Lebensstil und die regelmäßige Teilnahme an Vorsorgeuntersuchungen sind wichtig und können die Krebsmortalität von Diabetespatienten erheblich verringern.
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Affiliation(s)
- Hans Scherübl
- Klinik für Innere Medizin, Gastroenterologie, GI Onkologie, Diabetologie und Infektiologie, Vivantes Netzwerk für Gesundheit GmbH, Berlin, Germany
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Yasom S, Khumsri W, Boonsongserm P, Kitkumthorn N, Ruangvejvorachai P, Sooksamran A, Wanotayan R, Mutirangura A. B1 siRNA Increases de novo DNA Methylation of B1 Elements and Promotes Wound Healing in Diabetic Rats. Front Cell Dev Biol 2022; 9:802024. [PMID: 35127718 PMCID: PMC8807477 DOI: 10.3389/fcell.2021.802024] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2021] [Accepted: 12/22/2021] [Indexed: 11/13/2022] Open
Abstract
Alu (B1 in rodents) hypomethylation, commonly found in diabetes mellitus patients, increases DNA damage and, consequently, delays the healing process. Alu siRNA increases Alu methylation, reduces DNA damage, and promotes cell proliferation.Aim: To explore whether B1 siRNA treatment restores B1 hypomethylation, resulting in a reduction in DNA damage and acceleration of the healing process in diabetic rat wounds.Methods: We generated splinted-excisional wounds in a streptozotocin (STZ)-induced type I diabetic rat model and treated the wounds with B1 siRNA/Ca-P nanoparticles to generate de novo DNA methylation in B1 intersperse elements. After treatment, we investigated B1 methylation levels, wound closure rate, wound histopathological structure, and DNA damage markers in diabetic wounds compared to nondiabetic wounds.Results: We reported that STZ-induced diabetic rat wounds exhibited B1 hypomethylation, wound repair defects, anatomical feature defects, and greater DNA damage compared to normal rats. We also determined that B1 siRNA treatment by Ca-P nanoparticle delivery restored a decrease in B1 methylation levels, remedied delayed wound healing, and improved the histological appearance of the wounds by reducing DNA damage.Conclusion: B1 hypomethylation is inducible in an STZ-induced type I diabetes rat model. Restoration of B1 hypomethylation using B1 siRNA leads to increased genome stability and improved wound repair in diabetes. Thus, B1 siRNA intervention may be a promising strategy for reprogramming DNA methylation to treat or prevent DNA damage-related diseases.
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Affiliation(s)
- Sakawdaurn Yasom
- Center of Excellence in Molecular Genetics of Cancer and Human Disease, Department of Anatomy, Faculty of Medicine, King Chulalongkorn Memorial Hospital, Chulalongkorn University, Bangkok, Thailand
- Interdisciplinary Program of Biomedical Sciences, Graduate School, Chulalongkorn University, Bangkok, Thailand
| | - Wilunplus Khumsri
- Center of Excellence in Molecular Genetics of Cancer and Human Disease, Department of Anatomy, Faculty of Medicine, King Chulalongkorn Memorial Hospital, Chulalongkorn University, Bangkok, Thailand
- Interdisciplinary Program of Biomedical Sciences, Graduate School, Chulalongkorn University, Bangkok, Thailand
| | - Papatson Boonsongserm
- Center of Excellence in Molecular Genetics of Cancer and Human Disease, Department of Anatomy, Faculty of Medicine, King Chulalongkorn Memorial Hospital, Chulalongkorn University, Bangkok, Thailand
| | - Nakarin Kitkumthorn
- Department of Oral Biology, Faculty of Dentistry, Mahidol University, Bangkok, Thailand
| | | | - Apasee Sooksamran
- Department of Pathology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Rujira Wanotayan
- Department of Radiological Technology, Faculty of Medical Technology, Mahidol University, Nakhon Pathom, Thailand
| | - Apiwat Mutirangura
- Center of Excellence in Molecular Genetics of Cancer and Human Disease, Department of Anatomy, Faculty of Medicine, King Chulalongkorn Memorial Hospital, Chulalongkorn University, Bangkok, Thailand
- *Correspondence: Apiwat Mutirangura,
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33
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Sublethal concentrations of high glucose prolong mitotic arrest in a spindle assembly checkpoint activity dependent manner in budding yeast. Biologia (Bratisl) 2021. [DOI: 10.1007/s11756-021-00912-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
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Vekic J, Zeljkovic A, Stefanovic A, Giglio RV, Ciaccio M, Rizzo M. Diabetes and Colorectal Cancer Risk: A New Look at Molecular Mechanisms and Potential Role of Novel Antidiabetic Agents. Int J Mol Sci 2021; 22:12409. [PMID: 34830295 PMCID: PMC8622770 DOI: 10.3390/ijms222212409] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2021] [Revised: 11/14/2021] [Accepted: 11/15/2021] [Indexed: 12/13/2022] Open
Abstract
Epidemiological data have demonstrated a significant association between the presence of type 2 diabetes mellitus (T2DM) and the development of colorectal cancer (CRC). Chronic hyperglycemia, insulin resistance, oxidative stress, and inflammation, the processes inherent to T2DM, also play active roles in the onset and progression of CRC. Recently, small dense low-density lipoprotein (LDL) particles, a typical characteristic of diabetic dyslipidemia, emerged as another possible underlying link between T2DM and CRC. Growing evidence suggests that antidiabetic medications may have beneficial effects in CRC prevention. According to findings from a limited number of preclinical and clinical studies, glucagon-like peptide-1 receptor agonists (GLP-1RAs) could be a promising strategy in reducing the incidence of CRC in patients with diabetes. However, available findings are inconclusive, and further studies are required. In this review, novel evidence on molecular mechanisms linking T2DM with CRC development, progression, and survival will be discussed. In addition, the potential role of GLP-1RAs therapies in CRC prevention will also be evaluated.
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Affiliation(s)
- Jelena Vekic
- Department of Medical Biochemistry, Faculty of Pharmacy, University of Belgrade, 11000 Belgrade, Serbia; (J.V.); (A.Z.); (A.S.)
| | - Aleksandra Zeljkovic
- Department of Medical Biochemistry, Faculty of Pharmacy, University of Belgrade, 11000 Belgrade, Serbia; (J.V.); (A.Z.); (A.S.)
| | - Aleksandra Stefanovic
- Department of Medical Biochemistry, Faculty of Pharmacy, University of Belgrade, 11000 Belgrade, Serbia; (J.V.); (A.Z.); (A.S.)
| | - Rosaria Vincenza Giglio
- Department of Biomedicine, Neuroscience and Advanced Diagnostics, University of Palermo, 90100 Palermo, Italy; (R.V.G.); (M.C.)
| | - Marcello Ciaccio
- Department of Biomedicine, Neuroscience and Advanced Diagnostics, University of Palermo, 90100 Palermo, Italy; (R.V.G.); (M.C.)
- Department of Laboratory Medicine, University Hospital, 90100 Palermo, Italy
| | - Manfredi Rizzo
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, 90100 Palermo, Italy
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Haider N, Lebastchi J, Jayavelu AK, Batista TM, Pan H, Dreyfuss JM, Carcamo-Orive I, Knowles JW, Mann M, Kahn CR. Signaling defects associated with insulin resistance in nondiabetic and diabetic individuals and modification by sex. J Clin Invest 2021; 131:e151818. [PMID: 34506305 DOI: 10.1172/jci151818] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2021] [Accepted: 08/26/2021] [Indexed: 11/17/2022] Open
Abstract
Insulin resistance is present in one-quarter of the general population, predisposing these people to a wide range of diseases. Our aim was to identify cell-intrinsic determinants of insulin resistance in this population using induced pluripotent stem cell-derived (iPSC-derived) myoblasts (iMyos). We found that these cells exhibited a large network of altered protein phosphorylation in vitro. Integrating these data with data from type 2 diabetic iMyos revealed critical sites of conserved altered phosphorylation in IRS-1, AKT, mTOR, and TBC1D1 in addition to changes in protein phosphorylation involved in Rho/Rac signaling, chromatin organization, and RNA processing. There were also striking differences in the phosphoproteome in cells from men versus women. These sex-specific and insulin-resistance defects were linked to functional differences in downstream actions. Thus, there are cell-autonomous signaling alterations associated with insulin resistance within the general population and important differences between men and women, many of which also occur in diabetes, that contribute to differences in physiology and disease.
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Affiliation(s)
- Nida Haider
- Section of Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts, USA
| | - Jasmin Lebastchi
- Section of Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts, USA.,Division of Endocrinology, Brown, Alpert Medical School, Providence, Rhode Island, USA
| | - Ashok Kumar Jayavelu
- Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, Germany
| | - Thiago M Batista
- Section of Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts, USA
| | - Hui Pan
- Bioinformatics and Biostatistics Core, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts, USA
| | - Jonathan M Dreyfuss
- Bioinformatics and Biostatistics Core, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts, USA
| | - Ivan Carcamo-Orive
- Division of Cardiovascular Medicine, Cardiovascular Institute and Diabetes Research Center, Stanford University School of Medicine, Stanford, California, USA
| | - Joshua W Knowles
- Division of Cardiovascular Medicine, Cardiovascular Institute and Diabetes Research Center, Stanford University School of Medicine, Stanford, California, USA
| | - Matthias Mann
- Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, Germany
| | - C Ronald Kahn
- Section of Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts, USA
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Balkrishna A, Kumar A, Arya V, Rohela A, Verma R, Nepovimova E, Krejcar O, Kumar D, Thakur N, Kuca K. Phytoantioxidant Functionalized Nanoparticles: A Green Approach to Combat Nanoparticle-Induced Oxidative Stress. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2021; 2021:3155962. [PMID: 34737844 PMCID: PMC8563134 DOI: 10.1155/2021/3155962] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/30/2021] [Revised: 09/19/2021] [Accepted: 10/04/2021] [Indexed: 12/14/2022]
Abstract
Nanotechnology is gaining significant attention, with numerous biomedical applications. Silver in wound dressings, copper oxide and silver in antibacterial preparations, and zinc oxide nanoparticles as a food and cosmetic ingredient are common examples. However, adverse effects of nanoparticles in humans and the environment from extended exposure at varied concentrations have yet to be established. One of the drawbacks of employing nanoparticles is their tendency to cause oxidative stress, a significant public health concern with life-threatening consequences. Cardiovascular, renal, and respiratory problems and diabetes are among the oxidative stress-related disorders. In this context, phytoantioxidant functionalized nanoparticles could be a novel and effective alternative. In addition to performing their intended function, they can protect against oxidative damage. This review was designed by searching through various websites, books, and articles found in PubMed, Science Direct, and Google Scholar. To begin with, oxidative stress, its related diseases, and the mechanistic basis of oxidative damage caused by nanoparticles are discussed. One of the main mechanisms of action of nanoparticles was unearthed to be oxidative stress, which limits their use in humans. Secondly, the role of phytoantioxidant functionalized nanoparticles in oxidative damage prevention is critically discussed. The parameters for the characterization of nanoparticles were also discussed. The majority of silver, gold, iron, zinc oxide, and copper nanoparticles produced utilizing various plant extracts were active free radical scavengers. This potential is linked to several surface fabricated phytoconstituents, such as flavonoids and phenols. These phytoantioxidant functionalized nanoparticles could be a better alternative to nanoparticles prepared by other existing approaches.
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Affiliation(s)
- Acharya Balkrishna
- Patanjali Herbal Research Department, Patanjali Research Institute, Haridwar 249405, India
- Department of Allied Sciences, University of Patanjali, Haridwar 249405, India
| | - Ashwani Kumar
- Patanjali Herbal Research Department, Patanjali Research Institute, Haridwar 249405, India
| | - Vedpriya Arya
- Patanjali Herbal Research Department, Patanjali Research Institute, Haridwar 249405, India
- Department of Allied Sciences, University of Patanjali, Haridwar 249405, India
| | - Akansha Rohela
- Patanjali Herbal Research Department, Patanjali Research Institute, Haridwar 249405, India
| | - Rachna Verma
- School of Biological and Environmental Sciences, Shoolini University of Biotechnology and Management Sciences, Solan 173229, India
| | - Eugenie Nepovimova
- Department of Chemistry, Faculty of Science, University of Hradec Kralove, Hradec Kralove 50003, Czech Republic
| | - Ondrej Krejcar
- Center for Basic and Applied Science, Faculty of Informatics and Management, University of Hradec Kralove, 50003 Hradec Kralove, Czech Republic
- Malaysia Japan International Institute of Technology (MJIIT), Universiti Teknologi Malaysia, Jalan Sultan Yahya Petra, Kuala Lumpur 54100, Malaysia
| | - Dinesh Kumar
- School of Bioengineering and Food Technology, Shoolini University of Biotechnology and Management Sciences, Solan 173229, India
| | - Naveen Thakur
- Department of Physics, Career Point University, Hamirpur 177001, India
| | - Kamil Kuca
- Department of Chemistry, Faculty of Science, University of Hradec Kralove, Hradec Kralove 50003, Czech Republic
- Biomedical Research Center, University Hospital in Hradec Kralove, Sokolska 581, Hradec Kralove 50005, Czech Republic
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Liguori F, Mascolo E, Vernì F. The Genetics of Diabetes: What We Can Learn from Drosophila. Int J Mol Sci 2021; 22:ijms222011295. [PMID: 34681954 PMCID: PMC8541427 DOI: 10.3390/ijms222011295] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2021] [Revised: 10/12/2021] [Accepted: 10/16/2021] [Indexed: 12/14/2022] Open
Abstract
Diabetes mellitus is a heterogeneous disease characterized by hyperglycemia due to impaired insulin secretion and/or action. All diabetes types have a strong genetic component. The most frequent forms, type 1 diabetes (T1D), type 2 diabetes (T2D) and gestational diabetes mellitus (GDM), are multifactorial syndromes associated with several genes’ effects together with environmental factors. Conversely, rare forms, neonatal diabetes mellitus (NDM) and maturity onset diabetes of the young (MODY), are caused by mutations in single genes. Large scale genome screenings led to the identification of hundreds of putative causative genes for multigenic diabetes, but all the loci identified so far explain only a small proportion of heritability. Nevertheless, several recent studies allowed not only the identification of some genes as causative, but also as putative targets of new drugs. Although monogenic forms of diabetes are the most suited to perform a precision approach and allow an accurate diagnosis, at least 80% of all monogenic cases remain still undiagnosed. The knowledge acquired so far addresses the future work towards a study more focused on the identification of diabetes causal variants; this aim will be reached only by combining expertise from different areas. In this perspective, model organism research is crucial. This review traces an overview of the genetics of diabetes and mainly focuses on Drosophila as a model system, describing how flies can contribute to diabetes knowledge advancement.
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Affiliation(s)
- Francesco Liguori
- Preclinical Neuroscience, IRCCS Santa Lucia Foundation, 00143 Rome, Italy;
| | - Elisa Mascolo
- Department of Biology and Biotechnology “Charles Darwin”, Sapienza University, 00185 Rome, Italy;
| | - Fiammetta Vernì
- Department of Biology and Biotechnology “Charles Darwin”, Sapienza University, 00185 Rome, Italy;
- Correspondence:
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Park YH, Moon HW, Cho HJ, Ha US, Hong SH, Lee JY, Kim SW, Han K, Ko SH. Cumulative obesity exposure increases the risk of kidney cancer: a longitudinal nationwide cohort study. Am J Cancer Res 2021; 11:5016-5026. [PMID: 34765308 PMCID: PMC8569344] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2021] [Accepted: 07/26/2021] [Indexed: 06/13/2023] Open
Abstract
Obesity is one of the most important prognostic factors of kidney cancer. However, little is known regarding the cumulative impacts of obesity on kidney cancer risk. We aimed to analyze the dose- and time-dependent impact of obesity on kidney cancer risk using the Korean National Health Insurance System database. This longitudinal nationwide cohort study used data from the Korean National Health Insurance System database between 2012 and 2013. In total, 3,102,240 participants who received annual health examination more than four times consecutively were included in the final analysis. The primary endpoint was newly diagnosed kidney cancer according to the dose- and time-dependent impact of obesity. Dose-dependent impact was measured using body mass index (BMI) and waist circumference (WC), and time-dependent impact was measured using general and abdominal cumulative obesity exposure (gCOE and aCOE). COE was defined as the number of years since obesity diagnosis during the exposure period. We identified 1,831 participants with newly diagnosed kidney cancer (median follow-up: 4.3 years). The hazard ratios (HRs) for kidney cancer increased significantly alongside BMI and WC. The HRs for kidney cancer increased significantly in the higher gCOE groups (P for trend <0.001) as follows: 1 (1.33, 95% confidence intervals: 1.10-1.60), 2 (1.33, 1.08-1.63), 3 (1.55, 1.30-1.85), and 4 (1.82, 1.64-2.03) years. Similar trends were observed for aCOE (P for trend <0.001) as follows: 1 (1.42, 1.23-1.64), 2 (1.71, 1.46-2.02), 3 (1.76, 1.48-2.08), and 4 (2.11, 1.84-2.42) years. Risks of kidney cancer related to COE were much more pronounced in participants with the following characteristics: younger than 65 years old, male gender, diabetes, hypertension, and dyslipidemia. Longer COE was associated with an increased risk of kidney cancer in the Korean population. Participants with prolonged obesity and metabolic syndrome need active surveillance for kidney cancer.
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Affiliation(s)
- Yong Hyun Park
- Department of Urology, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of KoreaSeoul, Republic of Korea
| | - Hyong Woo Moon
- Department of Urology, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of KoreaSeoul, Republic of Korea
| | - Hyuk Jin Cho
- Department of Urology, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of KoreaSeoul, Republic of Korea
| | - U-Syn Ha
- Department of Urology, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of KoreaSeoul, Republic of Korea
| | - Sung-Hoo Hong
- Department of Urology, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of KoreaSeoul, Republic of Korea
| | - Ji Youl Lee
- Department of Urology, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of KoreaSeoul, Republic of Korea
| | - Sae Woong Kim
- Department of Urology, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of KoreaSeoul, Republic of Korea
| | - Kyungdo Han
- Department of Statistics and Actuarial Science, Soongsil UniversitySeoul, Republic of Korea
| | - Seung-Hyun Ko
- Division of Endocrinology and Metabolism, Department of Internal Medicine, St. Vincent’s Hospital, College of Medicine, The Catholic University of KoreaSeoul, Republic of Korea
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Scherübl H. [Type-2-diabetes and cancer risk]. Dtsch Med Wochenschr 2021; 146:1218-1225. [PMID: 34521128 DOI: 10.1055/a-1529-4521] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
Type-2-diabetes (T2D) increases the risk for several cancers and cancer has become the major cause of death of T2D-patients. T2D is causally associated with colorectal, pancreatic, gallbladder, biliary, hepatocellular, gastric, esophageal, oral, breast, endometrial, ovary, kidney and thyroid cancers as well as leukemias. When T2D goes along with tobacco smoking, alcohol use, physical inactivity, excess body weight, poor diet, familial risk or certain chronic infections, the cumulative cancer risk rises, and T2D-patients often suffer from cancer disease at younger age. T2D-patients should be encouraged to join cancer screening programmes even at younger age than the average non-diabetic population.
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Farahani-Zangaraki M, Taheri A, Etebari M. Niosome-carvedilol protects DNA damage of supraphysiologic concentrations of insulin using comet assay: An in vitro study. Hum Exp Toxicol 2021; 40:S150-S157. [PMID: 34334013 DOI: 10.1177/09603271211036124] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Introduction: Hyperinsulinemia occurs in type 2 diabetic patients with insulin resistance. This increase in insulin levels in the blood increases reactive oxygen species production and oxidative stress, resulting in DNA damage. Carvedilol (CRV) is a non-selective beta-blocker, and research has shown that this compound and its metabolites have anti-oxidative properties. Carvedilol can, directly and indirectly, reduce reactive oxygen species (ROS) and has a protective effect on DNA damage from oxidative stress. Given the insolubility of CRV in water, finding new methods to increase its solubility can be an essential step in research. This study aimed to determine whether carvedilol could have a protective effect on insulin-induced genomic damage. Methods: We treated cells with insulin alone, amorphous-CRV alone, and amorphous-CRV and niosomal-CRV with insulin and DNA damage were investigated using the comet method to achieve this goal. Results: Our results showed that insulin in the studied concentration has a significant genotoxic effect and non-cytotoxic at higher concentrations. CRV, both in amorphous and niosome form, reduced insulin-induced DNA damage by reducing ROS production. The comet assay results demonstrate that treating HUVEC cells in pretreatment condition with amorphous-CRV and niosome-CRV significantly reduces DNA damage of insulin.
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Affiliation(s)
- Marzieh Farahani-Zangaraki
- Faculty of Pharmacy and Pharmaceutical Sciences, Department of Pharmacology and Toxicology, 108868Isfahan University of Medical Sciences, Isfahan, Iran
| | - Azade Taheri
- Faculty of Pharmacy, Department of Pharmaceutics, 108868Isfahan University of Medical Sciences, Isfahan, Iran
| | - Mahmoud Etebari
- Faculty of Pharmacy and Pharmaceutical Sciences, Department of Pharmacology and Toxicology, and Isfahan Pharmaceutical Sciences Research Center, 108868Isfahan University of Medical Sciences, Isfahan, Iran
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Li YF, Shi LJ, Wang P, Wang JW, Shi GY, Lee SC. Binding between ROCK1 and DCTN2 triggers diabetes‑associated centrosome amplification in colon cancer cells. Oncol Rep 2021; 46:151. [PMID: 34080666 PMCID: PMC8185503 DOI: 10.3892/or.2021.8102] [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: 01/17/2021] [Accepted: 05/05/2021] [Indexed: 11/06/2022] Open
Abstract
Type 2 diabetes increases the risk various types of cancer and is associated with a poor prognosis therein. There is also evidence that the disease is associated with cancer metastasis. Centrosome amplification can initiate tumorigenesis with metastasis in vivo and increase the invasiveness of cancer cells in vitro. Our previous study reported that type 2 diabetes promotes centrosome amplification via the upregulation and centrosomal translocation of Rho-associated protein kinase 1 (ROCK1), which suggests that centrosome amplification is a candidate biological link between type 2 diabetes and cancer development. In the present study, functional proteomics analysis was used to further investigate the molecular pathways underlying centrosome amplification by targeting ROCK1 binding partners. High glucose, insulin and palmitic acid were used to induce centrosome amplification, and immunofluorescent staining was employed to visualize centrosomal alterations. Combined with immunoprecipitation, mass spectrometry-based proteomics analysis was used to identify ROCK1 binding proteins, and protein complex disruption was achieved by siRNA-knockdown. In total, 1,148 ROCK1 binding proteins were identified, among which 106 proteins were exclusively associated with the treated samples, 193 were only associated with the control samples, and 849 were found in both the control and treated samples. Of the proteins with evidence of centrosomal localization, Dynactin subunit 2 (DCTN2) was confirmed to be localized to the centrosomes. Treating the cells with high glucose, insulin and palmitic acid increased the protein levels of ROCK1 and DCTN2, promoted their binding with each other, and triggered centrosome amplification. Disruption of the protein complex by knocking down ROCK1 or DCTN2 expression partially attenuated centrosome amplification, while simultaneous knockdown of both proteins completely inhibited centrosome amplification. These results suggested ROCK1-DCTN2 binding as a signal for the regulation of centrosome homeostasis, which is key for diabetes-associated centrosome amplification, and enriches our knowledge of centrosome biology. Therefore, the ROCK1-DCTN2 complex may serve as a target for inhibiting centrosome amplification both in research or future therapeutic development.
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Affiliation(s)
- Yuan Fei Li
- Department of Oncology, The First Hospital, Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China
| | - Lin Jie Shi
- Department of Oncology, The First Hospital, Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China
| | - Pu Wang
- Changzhi Medical University, Changzhi, Shanxi 030001, P.R. China
| | - Jia Wen Wang
- Institute of Biomedical Sciences of The School of Life Sciences, Jiangsu Normal University, Xuzhou, Jiangsu 221116, P.R. China
| | - Guang Yi Shi
- Institute of Biomedical Sciences of The School of Life Sciences, Jiangsu Normal University, Xuzhou, Jiangsu 221116, P.R. China
| | - Shao Chin Lee
- Institute of Biomedical Sciences of The School of Life Sciences, Jiangsu Normal University, Xuzhou, Jiangsu 221116, P.R. China
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Bhardwaj P, Brown KA. Obese Adipose Tissue as a Driver of Breast Cancer Growth and Development: Update and Emerging Evidence. Front Oncol 2021; 11:638918. [PMID: 33859943 PMCID: PMC8042134 DOI: 10.3389/fonc.2021.638918] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2020] [Accepted: 03/12/2021] [Indexed: 12/24/2022] Open
Abstract
Obesity is an established risk factor for breast cancer growth and progression. A number of advances have been made in recent years revealing new insights into this link. Early events in breast cancer development involve the neoplastic transformation of breast epithelial cells to cancer cells. In obesity, breast adipose tissue undergoes significant hormonal and inflammatory changes that create a mitogenic microenvironment. Many factors that are produced in obesity have also been shown to promote tumorigenesis. Given that breast epithelial cells are surrounded by adipose tissue, the crosstalk between the adipose compartment and breast epithelial cells is hypothesized to be a significant player in the initiation and progression of breast cancer in individuals with excess adiposity. The present review examines this crosstalk with a focus on obese breast adipose-derived estrogen, inflammatory mediators and adipokines, and how they are mechanistically linked to breast cancer risk and growth through stimulation of oxidative stress, DNA damage, and pro-oncogenic transcriptional programs. Pharmacological and lifestyle strategies targeting these factors and their downstream effects are evaluated for feasibility and efficacy in decreasing the risk of obesity-induced breast epithelial cell transformation and consequently, breast cancer development.
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Affiliation(s)
- Priya Bhardwaj
- Department of Medicine, Weill Cornell Medicine, New York, NY, United States
- Graduate School of Medical Sciences, Weill Cornell Medicine, New York, NY, United States
| | - Kristy A. Brown
- Department of Medicine, Weill Cornell Medicine, New York, NY, United States
- Graduate School of Medical Sciences, Weill Cornell Medicine, New York, NY, United States
- Meyer Cancer Center, Weill Cornell Medicine, New York, NY, United States
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Yan P, Wang Y, Fu T, Liu Y, Zhang ZJ. The association between type 1 and 2 diabetes mellitus and the risk of leukemia: a systematic review and meta-analysis of 18 cohort studies. Endocr J 2021; 68:281-289. [PMID: 33087643 DOI: 10.1507/endocrj.ej20-0138] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Diabetes mellitus (DM) is widely considered to be associated with the risk of diverse cancers; however, the association between DM and the risk of leukemia is still controversial. Thus, a detailed meta-analysis of cohort studies was conducted to elucidate this association. Eligible studies were screened through the electronic searches in PubMed, Web of Science, and Embase from their inception to August 11, 2020. Summary relative risks (RRs) and 95% confidence intervals (CIs) were computed through the random-effects model. Eighteen articles involving 10,516 leukemia cases among a total of 4,094,235 diabetic patients were included in this meta-analysis. Overall, twenty-five RRs were synthesized for type 2 diabetes mellitus (T2DM) and yielded a summary RR of 1.33 (95%CI, 1.21-1.47; p < 0.001). For type 1 diabetes mellitus (T1DM), 7 RRs were combined, however, the pooled RR was insignificant (RR, 1.08; 95%CI, 0.87-1.34; p = 0.48). Interestingly, the summary RR for East Asia (RR, 1.83, 95%CI, 1.63-2.06) was significantly higher than that for Europe (RR, 1.11, 95%CI, 1.06-1.15), Western Asia (RR, 1.40, 95%CI, 1.25-1.54), North America (RR, 1.14, 95%CI, 1.08-1.20), and Australia (RR, 1.47, 95%CI, 1.25-1.71). Moreover, we found that patients with a shorter T2DM duration (1-5 years) had a higher risk of leukemia compared to those with a longer duration (5.1-10 years). Overall, this meta-analysis suggests there is a moderately increased risk of leukemia among T2DM patients, but not in T1DM patients. Further investigation is warranted.
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Affiliation(s)
- Pengfei Yan
- Department of Preventive Medicine, School of Health Sciences, Wuhan University, Wuhan 430071, China
| | - Yongbo Wang
- Center for Evidence-Based and Translational Medicine, Zhongnan Hospital of Wuhan University, Wuhan 430071, China
| | - Tao Fu
- Department of Gastrointestinal Surgery II, Renmin Hospital, Wuhan University, Wuhan 430060, China
| | - Yu Liu
- Department of Statistics and Management, School of Management, Wuhan Institute of Technology, Wuhan 430205, China
| | - Zhi-Jiang Zhang
- Department of Preventive Medicine, School of Health Sciences, Wuhan University, Wuhan 430071, China
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Nutritional, phytochemical, and in vitro anticancer potential of sugar apple (Annona squamosa) fruits. Sci Rep 2021; 11:6224. [PMID: 33737634 PMCID: PMC7973736 DOI: 10.1038/s41598-021-85772-8] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2021] [Accepted: 02/28/2021] [Indexed: 02/05/2023] Open
Abstract
In plants, Fruits and their wastes are the main sources of bioactive compounds. Currently, Annona fruits have attracted the attention of people interested in health-promoting foods due to their phytochemical content that their activities were not studied before. This study aimed to explore the potential antioxidant, antimicrobial, and in vitro anticancer activity of two cultivars Annona squamosa (Annona b. and Annona h.) seed, peel, and pulp. We also meausred phenolic, flavonoid, sulfated polysaccharide, tannins, and triterpenoids. Polyphenol identification was determined using RP-HPLC. Results of the antioxidant activity revealed that the highest activity was observed for Annona h. seed extract using DPPH and ABTS assays with IC50 6.07 ± 0.50 and 9.58 ± 0.53 µg/ml, respectively. The antimicrobial activity against various pathogenic strains revealed that the peel extracts of both Annona b. and Annona h. exhibited the best antimicrobial activity. We also assessed the IC50 values for anticancer activity in all six Annona b. and Annona h samples against four cancer cell lines colon (Caco-2), prostate (PC3), liver (HepG-2), and breast (MCF-7) using MTT assay. Annona b. and Annona h seed extracts had the lowest IC50 values for four cancer cell lines with 7.31 ± 0.03 and 15.99 ± 1.25 for PC-3 and MCF-7, respectively. Both seed extracts, Annona b. and Annona h., showed significantly down-regulated mRNA expression of Bcl-2 and up-regulated p53 in all treated cell lines. Apoptosis was evaluated using nuclear staining, flow cytometric analysis, and immunohistochemistry of the proliferation marker (Ki-67). Additional studies are required to characterize the bioactive compounds responsible for the observed activities of Annona seed and determine its mechanism as an anticancer drug.
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Proteomics Analysis of Gastric Cancer Patients with Diabetes Mellitus. J Clin Med 2021; 10:jcm10030407. [PMID: 33494396 PMCID: PMC7866049 DOI: 10.3390/jcm10030407] [Citation(s) in RCA: 39] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2020] [Revised: 01/15/2021] [Accepted: 01/16/2021] [Indexed: 12/13/2022] Open
Abstract
Proteomics is a powerful approach to study the molecular mechanisms of cancer. In this study, we aim to characterize the proteomic profile of gastric cancer (GC) in patients with diabetes mellitus (DM) type 2. Forty GC tissue samples including 19 cases from diabetic patients and 21 cases from individuals without diabetes (control group) were selected for the proteomics analysis. Gastric tissues were processed following the single-pot, solid-phase-enhanced sample preparation approach-SP3 and enzymatic digestion with trypsin. The resulting peptides were analyzed by LC-MS Liquid Chromatography-Mass Spectrometry (LC-MS). The comparison of protein expression levels between GC samples from diabetic and non-diabetic patients was performed by label-free quantification (LFQ). A total of 6599 protein groups were identified in the 40 samples. Thirty-seven proteins were differentially expressed among the two groups, with 16 upregulated and 21 downregulated in the diabetic cohort. Statistical overrepresentation tests were considered for different annotation sets including the Gene Ontology(GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Reactome, and Disease functional databases. Upregulated proteins in the GC samples from diabetic patients were particularly enriched in respiratory electron transport and alcohol metabolic biological processes, while downregulated proteins were associated with epithelial cancers, intestinal diseases, and cell-cell junction cellular components. Taken together, these results support the data already obtained by previous studies that associate diabetes with metabolic disorders and diabetes-associated diseases, such as Alzheimer's and Parkinson's, and also provide valuable insights into seven GC-associated protein targets, claudin-3, polymeric immunoglobulin receptor protein, cadherin-17, villin-1, transglutaminase-2, desmoglein-2, and mucin-13, which warrant further investigation.
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Etebari M, Naghsh-Nilchi F. Attenuation of hyperinsulinemia-induced DNA damage of peripheral lymphocytes by carvedilol. JOURNAL OF REPORTS IN PHARMACEUTICAL SCIENCES 2021. [DOI: 10.4103/jrptps.jrptps_1_21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
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Crigna AT, Samec M, Koklesova L, Liskova A, Giordano FA, Kubatka P, Golubnitschaja O. Cell-free nucleic acid patterns in disease prediction and monitoring-hype or hope? EPMA J 2020; 11:603-627. [PMID: 33144898 PMCID: PMC7594983 DOI: 10.1007/s13167-020-00226-x] [Citation(s) in RCA: 58] [Impact Index Per Article: 11.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2020] [Accepted: 10/07/2020] [Indexed: 02/07/2023]
Abstract
Interest in the use of cell-free nucleic acids (CFNAs) as clinical non-invasive biomarker panels for prediction and prevention of multiple diseases has greatly increased over the last decade. Indeed, circulating CFNAs are attributable to many physiological and pathological processes such as imbalanced stress conditions, physical activities, extensive apoptosis of different origin, systemic hypoxic-ischemic events and tumour progression, amongst others. This article highlights the involvement of circulating CFNAs in local and systemic processes dealing with the question, whether specific patterns of CFNAs in blood, their detection, quantity and quality (such as their methylation status) might be instrumental to predict a disease development/progression and could be further utilised for accompanying diagnostics, targeted prevention, creation of individualised therapy algorithms, therapy monitoring and prognosis. Presented considerations conform with principles of 3P medicine and serve for improving individual outcomes and cost efficacy of medical services provided to the population.
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Affiliation(s)
- Adriana Torres Crigna
- Department of Radiation Oncology, University Hospital Bonn, Rheinische Friedrich-Wilhelms-Universität Bonn, Bonn, Germany
| | - Marek Samec
- Department of Obstetrics and Gynecology, Jessenius Faculty of Medicine, Comenius University in Bratislava, 03601 Martin, Slovakia
| | - Lenka Koklesova
- Department of Obstetrics and Gynecology, Jessenius Faculty of Medicine, Comenius University in Bratislava, 03601 Martin, Slovakia
| | - Alena Liskova
- Department of Obstetrics and Gynecology, Jessenius Faculty of Medicine, Comenius University in Bratislava, 03601 Martin, Slovakia
| | - Frank A. Giordano
- Department of Radiation Oncology, University Hospital Bonn, Rheinische Friedrich-Wilhelms-Universität Bonn, Bonn, Germany
| | - Peter Kubatka
- Department of Medical Biology, Jessenius Faculty of Medicine, Comenius University in Bratislava, 03601 Martin, Slovakia
| | - Olga Golubnitschaja
- Predictive, Preventive, Personalised (3P) Medicine, Department of Radiation Oncology, University Hospital Bonn, Rheinische Friedrich-Wilhelms-Universität Bonn, Bonn, Germany
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Banerjee S, Biswas TK, Chattopadhyay K, Arzoo SH, Chattopadhyay B. An Approach to Screen Genotoxic-Susceptible Diabetic Population of Various Prakriti Groups for Personalized Disease Management. J Altern Complement Med 2020; 27:80-87. [PMID: 33074706 DOI: 10.1089/acm.2020.0001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
Background: Ayurveda classifies human populations into three predominant groups as Vata, Pitta, and Kapha based on their "Prakriti'. Any disturbance in the equilibrium of Prakriti can cause various diseases. Objectives: The aim of the study was to link genotoxic variation among the three Prakriti having type 2 diabetes. Design: Type 2 diabetic patients and healthy individuals belonging to three predominant Prakriti were selected through the Prakriti Questionnaire screening as per the guidelines of the CSIR-TRISUTRA unit modified for type 2 diabetes disease. Settings/Location: Sixty individuals from three predominant Prakriti, each consisting of 10 diabetic patients and 10 healthy individuals, were chosen. Subjects: Clinically diagnosed outdoor patients of JBRMCH suffering from type 2 diabetes for 5 years (fasting blood glucose >140 mg/dL; HbA1C > 7.0) and healthy individuals were the subjects for study. Inclusion Criteria: Age limit: 30-70 years, Sex: Both, Habitant: Participants residing in West Bengal for the last five generations, Religion: Unspecified, Social entity: Both urban and rural, Education: High school to college, Economic status: Lower middle to middle classes. Exclusion Criteria: Participants were nonsmokers and nonalcoholics. An individual having a medical history of long-term illness or dwandaja Prakriti type was excluded here. Outcome Measures: Reactive oxygen species (ROS) generation, blood DNA content, DNA damage, apoptosis of blood cells, and interaction of DNA with various carcinogens were observed. Results: The yield of ROS and total cell damage were significantly higher in the diabetic Vata (p < 0.001) group compared with other Prakriti Decreased DNA content and increased DNA damage were observed in type 2 diabetic patients who belonged to Vata (p < 0.01) Prakriti. DNA of Vata Prakriti was more prone to lead and arsenic. Conclusions: The diabetic Vata Prakriti is a genetically susceptible group as it has a tendency to get affected by increased DNA damage, which could help in creating personalized management of diabetes among individual Prakriti.
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Affiliation(s)
| | - Tuhin Kanti Biswas
- Research Unit, J. B. Roy State Ayurvedic Medical College and Hospital, Kolkata, India
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Ruze R, Xiong YC, Li JW, Zhong MW, Xu Q, Yan ZB, Zhu JK, Cheng YG, Hu SY, Zhang GY. Sleeve gastrectomy ameliorates endothelial function and prevents lung cancer by normalizing endothelin-1 axis in obese and diabetic rats. World J Gastroenterol 2020; 26:2599-2617. [PMID: 32523314 PMCID: PMC7265138 DOI: 10.3748/wjg.v26.i20.2599] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2020] [Revised: 04/13/2020] [Accepted: 05/15/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Previous evidence has implied that obesity is an independent risk factor for developing cancer. Being closely related to obesity, type 2 diabetes mellitus provides a suitable environment for the formation and metastasis of tumors through multiple pathways. Although bariatric surgeries are effective in preventing and lowering the risk of various types of cancer, the underlying mechanisms of this effect are not clearly elucidated.
AIM To uncover the role and effect of sleeve gastrectomy (SG) in preventing lung cancer in obese and diabetic rats.
METHODS SG was performed on obese and diabetic Wistar rats, and the postoperative transcriptional and translational alterations of the endothelin-1 (ET-1) axis in the lungs were compared to sham-operated obese and diabetic rats and age-matched healthy controls to assess the improvements in endothelial function and risk of developing lung cancer at the postoperative 4th, 8th, and 12th weeks. The risk was also evaluated using nuclear phosphorylation of H2A histone family member X as a marker of DNA damage (double-strand break).
RESULTS Compared to obese and diabetic sham-operated rats, SG brought a significant reduction to body weight, food intake, and fasting blood glucose while improving oral glucose tolerance and insulin sensitivity. In addition, ameliorated levels of gene and protein expression in the ET-1 axis as well as reduced DNA damage indicated improved endothelial function and a lower risk of developing lung cancer after the surgery.
CONCLUSION Apart from eliminating metabolic disorders, SG improves endothelial function and plays a protective role in preventing lung cancer via normalized ET-1 axis and reduced DNA damage.
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Affiliation(s)
- Rexiati Ruze
- Department of General Surgery, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan 250014, Shandong Province, China
| | - Ya-Cheng Xiong
- Department of General Surgery, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan 250014, Shandong Province, China
| | - Jian-Wen Li
- Department of General Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China
| | - Ming-Wei Zhong
- Department of General Surgery, The First Affiliated Hospital of Shandong First Medical University, Jinan 250014, Shandong Province, China
| | - Qian Xu
- Department of General Surgery, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan 250014, Shandong Province, China
| | - Zhi-Bo Yan
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan 250012, Shandong Province, China
| | - Jian-Kang Zhu
- Department of General Surgery, The First Affiliated Hospital of Shandong First Medical University, Jinan 250014, Shandong Province, China
| | - Yu-Gang Cheng
- Department of General Surgery, The First Affiliated Hospital of Shandong First Medical University, Jinan 250014, Shandong Province, China
| | - San-Yuan Hu
- Department of General Surgery, The First Affiliated Hospital of Shandong First Medical University, Jinan 250014, Shandong Province, China
| | - Guang-Yong Zhang
- Department of General Surgery, The First Affiliated Hospital of Shandong First Medical University, Jinan 250014, Shandong Province, China
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Abudawood M, Tabassum H, Almaarik B, Aljohi A. Interrelationship between oxidative stress, DNA damage and cancer risk in diabetes (Type 2) in Riyadh, KSA. Saudi J Biol Sci 2020; 27:177-183. [PMID: 31889833 PMCID: PMC6933234 DOI: 10.1016/j.sjbs.2019.06.015] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2019] [Revised: 06/10/2019] [Accepted: 06/23/2019] [Indexed: 12/20/2022] Open
Abstract
Type 2 Diabetes Mellitus (T2DM) is the most widely known type of disorder of the endocrine system marked by hyperglycemia resulting either due to deficiency of insulin and or resistance. Persistent hyperglycemia induces oxidative stress and is suggested to play a prominent role in the pathophysiology underlying T2DM. Besides, oxidative stress can result in DNA damage leading to high cancer risk. Current study aimed to evaluate status of oxidative damage, damage to DNA and cancer biomarkers in regard to increased glucose in T2DM patients and to correlate the glycemic state with cancer. A total of 150 subjects consisting of control (50) and T2DM patients (1 0 0) were enrolled. Additionally, three tertiles were created among the two groups based on levels of HbA1c (Tertile I = 5.37 ± 0.34, n = 50; Tertile II = 6.74 ± 0.20, n = 50; Tertile III = 9.21 ± 1.47, n = 50). Oxidative stress parameters including malondialedehyde (MDA) and antioxidant enzymes were measured. Damage to DNA was analyzed by measuring the levels of DNA damage adduct-8 hydroxy deoxy Guanosine (8-OHdG). To detect cancer resulting from oxidative stress, cancer biomarkers CEA, AFP, CA125, CA-15, CA19-9, prolactin were measured in these subjects. All measurements were analysed by SPSS software. Levels of MDA and antioxidant enzymes altered significantly in T2DM group at p < 0.001 and p < 0.05 level of significance. Significant DNA damage accompanied with elevated levels of CEA, CA19-9 and decreased CA125, AFP and prolactin were noted in T2DM group. CA 19-9 and CEA levels increased at p < 0.05, whereas levels of prolactin decreased significantly (p < 0.001) in T2DM group compared to control. Additionally the mean values of DNA damage adduct 8-OHdG differ significantly at P < 0.01 between the two groups. However, no significant correlation in oxidative stress parameter, antioxidant enzymes, DNA damage and neither with the highest tertile of HbA1c (>7.5%) was noted. Based on the results obtained in the present study, we conclude that there is considerable change in oxidative stress and DNA damage in T2DM patients. Hence, assumption that the oxidative stress could cause cancer in T2DM as a result of hyperglycemic state was not speculated in this study.
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Affiliation(s)
- Manal Abudawood
- Clinical Laboratory Sciences, King Saud University, Riyadh, Saudi Arabia
| | - Hajera Tabassum
- Clinical Laboratory Sciences, King Saud University, Riyadh, Saudi Arabia
| | - Basmah Almaarik
- Clinical Laboratory Sciences, King Saud University, Riyadh, Saudi Arabia
| | - Ali Aljohi
- Central Military Laboratory & Blood Bank, Prince Sultan Military Medical City, Riyadh, Saudi Arabia
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