scholarly journals Plasma Metabolomics Reveals Metabolic Profiling For Diabetic Retinopathy and Disease Progression

2021 ◽  
Vol 12 ◽  
Author(s):  
Yu Sun ◽  
Huiling Zou ◽  
Xingjia Li ◽  
Shuhang Xu ◽  
Chao Liu
Keyword(s):  
Diabetic Retinopathy ◽  
Disease Progression ◽  
Risk Score ◽  
Vascular Complication ◽  
Differentially Expressed ◽  
Plasma Metabolites ◽  
Multivariate Statistical ◽  
Working Age ◽  
The Difference ◽  
Selection Operator

BackgroundsDiabetic retinopathy (DR), the main retinal vascular complication of DM, is the leading cause of visual impairment and blindness among working-age people worldwide. The aim of this study was to investigate the difference of plasma metabolic profiles in patients with DR to better understand the mechanism of this disease and disease progression.MethodsWe used ultrahigh-performance liquid Q-Exactive mass spectrometry and multivariate statistical analyses to conduct a comprehensive analysis of plasma metabolites in a population with DR and proliferative DR (PDR). A risk score based on the level of the selected metabolite was established and evaluated using the least absolute shrinkage and selection operator regularization logistic regression (LASSO-LR) based machine learning model.Results22 differentially expressed metabolites which belonged to different metabolic pathway were identified and confirmed to be associated with the occurrence of DR. A risk score based on the level of the selected metabolite pseudouridine was established and evaluated to strongly associated with the occurrence of DR. Four circulating plasma metabolites (pseudouridine, glutamate, leucylleucine and N-acetyltryptophan) were identified to be differentially expressed between patients with PDR and other patients, and a risk score formula based on these plasma metabolites was developed and assessed to be significantly related to PDR.ConclusionsOur work highlights the possible use of the risk score assessment based on the plasma metabolites not only reveal in the early diagnosis of DR and PDR but also assist in enhancing current therapeutic strategies in the clinic.

scholarly journals Difference in the Vitreal Protein Profiles of Patients with Proliferative Diabetic Retinopathy with and without Intravitreal Conbercept Injection

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Chen Zou ◽  
Minjie Zhao ◽  
Jingjing Yu ◽  
Dandan Zhu ◽  
Yunzhi Wang ◽  
...  
Keyword(s):  
Immune Response ◽  
Diabetic Retinopathy ◽  
Proliferative Diabetic Retinopathy ◽  
Protein Profile ◽  
Differentially Expressed ◽  
Differentially Expressed Proteins ◽  
Protein Profiles ◽  
Go Annotation ◽  
Liquid Chromatography Tandem Mass ◽  
The Difference

Purpose. To examine the difference in the vitreal protein profiles of patients with proliferative diabetic retinopathy (PDR) with and without preoperative intravitreal conbercept (IVC) treatment. Methods. Liquid chromatography-tandem mass spectrometry- (LC-MS/MS-) based proteomic methods were used to determine the protein profiles of the vitreous humor in patients with PDR treated with (IVC group; n=9) and without (PDR group; n=8) preoperative IVC. Gene ontology (GO) annotation and REACTOME pathway analysis were obtained to overview differentially expressed proteins between each group. Intravitreal levels of apolipoprotein A-II (APOA2) and ceruloplasmin (CP) were measured using enzyme-linked immunosorbent assays. Results. 307 proteins were expressed differentially between PDR and IVC groups, including 218 proteins downregulated in response to IVC. The most notable GO annotations in level 3 and REACTOME pathways describing the differentially expressed proteins were “innate immune response” and “platelet degranulation.” The intravitreal levels of APOA2 and CP were lower in the IVC group than in the PDR group (p<0.01). Conclusions. In addition to decreasing the intravitreal vascular endothelial growth factor level, IVC may alter the vitreal protein profile in patients with PDR, with the differentially regulated proteins involved in the immune response, platelet degranulation, complement activation, and inflammation.

Polymorphisms of the Plasminogen Activator Inhibitor- 1 Gene in Type 1 and Type 2 Diabetes, and in Patients with Diabetic Retinopathy

1994 ◽  
Vol 71 (06) ◽  
pp. 731-736 ◽  
Author(s):  
M W Mansfield ◽  
M H Stickland ◽  
A M Carter ◽  
P J Grant
Keyword(s):  
Diabetic Retinopathy ◽  
Plasminogen Activator Inhibitor ◽  
Allelic Frequency ◽  
Repeat Sequence ◽  
Dinucleotide Repeat ◽  
Plasminogen Activator Inhibitor 1 ◽  
The Difference ◽  
Pai 1

SummaryTo identify whether genotype contributes to the difference in PAI-1 levels in type 1 and type 2 diabetic subjects and whether genotype relates to the development of retinopathy, a Hind III restriction fragment length polymorphism and two dinucleotide repeat polymorphisms were studied. In 519 Caucasian diabetic subjects (192 type 1, 327 type 2) and 123 Caucasian control subjects there were no differences in the frequency of the Hind III restriction alleles (type 1 vs type 2 vs control: allele 1 0.397 vs 0.420 vs 0.448; allele 2 0.603 vs 0.580 vs 0.552) nor in the allelic frequency at either dinucleotide repeat sequence. In 86 subjects with no retinopathy at 15 years or more from diagnosis of diabetes and 190 subjects with diabetic retinopathy there was no difference in the frequency of Hind III restriction alleles (retinopathy present vs retinopathy absent: allele 1 0.400 vs 0.467; allele 2 0.600 vs 0.533) nor in the allelic frequencies at either dinucleotide repeat sequence. The results indicate that there is no or minimal influence of the PAI-1 gene on either PAI-1 levels or the development of diabetic retinopathy in patients with diabetes mellitus.

scholarly journals Risk stratification scores for hospitalization duration and disease progression in moderate and severe patients with COVID-19

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jiaqi Huang ◽  
Yu Xu ◽  
Bin Wang ◽  
Ying Xiang ◽  
Na Wu ◽  
...  
Keyword(s):  
Platelet Count ◽  
Lactate Dehydrogenase ◽  
Risk Stratification ◽  
Disease Progression ◽  
Risk Score ◽  
Healthcare Providers ◽  
Maximum Body ◽  
Score Systems ◽  
Risk Categories ◽  
Risk Stratification Score

Abstract Background During outbreak of Coronavirus Disease 2019 (COVID-19), healthcare providers are facing critical clinical decisions based on the prognosis of patients. Decision support tools of risk stratification are needed to predict outcomes in patients with different clinical types of COVID-19. Methods This retrospective cohort study recruited 2425 patients with moderate or severe COVID-19. A logistic regression model was used to select and estimate the factors independently associated with outcomes. Simplified risk stratification score systems were constructed to predict outcomes in moderate and severe patients with COVID-19, and their performances were evaluated by discrimination and calibration. Results We constructed two risk stratification score systems, named as STPCAL (including significant factors in the prediction model: number of clinical symptoms, the maximum body temperature during hospitalization, platelet count, C-reactive protein, albumin and lactate dehydrogenase) and TRPNCLP (including maximum body temperature during hospitalization, history of respiratory diseases, platelet count, neutrophil-to-lymphocyte ratio, creatinine, lactate dehydrogenase, and prothrombin time), to predict hospitalization duration for moderate patients and disease progression for severe patients, respectively. According to STPCAL score, moderate patients were classified into three risk categories for a longer hospital duration: low (Score 0–1, median = 8 days, with less than 20.0% probabilities), intermediate (Score 2–6, median = 13 days, with 30.0–78.9% probabilities), high (Score 7–9, median = 19 days, with more than 86.5% probabilities). Severe patients were stratified into three risk categories for disease progression: low risk (Score 0–5, with less than 12.7% probabilities), intermediate risk (Score 6–11, with 18.6–69.1% probabilities), and high risk (Score 12–16, with more than 77.9% probabilities) by TRPNCLP score. The two risk scores performed well with good discrimination and calibration. Conclusions Two easy-to-use risk stratification score systems were built to predict the outcomes in COVID-19 patients with different clinical types. Identifying high risk patients with longer stay or poor prognosis could assist healthcare providers in triaging patients when allocating limited healthcare during COVID-19 outbreak.

scholarly journals The Severity of Diabetic Retinopathy Is an Independent Factor for the Progression of Diabetic Nephropathy

2020 ◽  
Vol 10 (1) ◽  
pp. 3
Author(s):  
Shi-Chue Hsing ◽  
Chia-Cheng Lee ◽  
Chin Lin ◽  
Jiann-Torng Chen ◽  
Yi-Hao Chen ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Diabetic Retinopathy ◽  
Kidney Disease ◽  
Renal Disease ◽  
Disease Progression ◽  
Renal Disease Progression ◽  
Hazard Ratios ◽  
Stage Renal Disease ◽  
End Stage

(1) Background: It has rarely been studied whether the severity of diabetic retinopathy (DR) could influence renal disease progression in end-stage renal disease (ESRD) and chronic kidney disease (CKD) in patients with type 2 diabetes. The aim of this study was to evaluate renal disease progression in ESRD and CKD according to DR severity in patients with type 2 diabetes. (2) Methods: We included 1329 patients and divided the cohort into two end-points. The first was to trace the incidence of ESRD in all enrolled participants and the other was to follow their progression to CKD. (3) Results: Significantly higher crude hazard ratios (HRs) of ESRD incidence in all enrolled participants were noted, and this ratio increased in a stepwise fashion. However, after adjustment, DR severity was not associated with ESRD events. Therefore, a subgroup of 841 patients without CKD was enrolled to track their progression to CKD. Compared with no diabetic retinopathy, the progression of CKD increased in a stepwise fashion, from mild nonproliferative diabetic retinopathy (NPDR) to moderate NPDR, to severe NPDR and to proliferative diabetic retinopathy (PDR), both in the crude and adjusted models. (4) Conclusions: The severity of retinopathy appeared to be associated with renal lesions and the development of CKD. Our findings suggest that the severity of DR is a risk factor for progression to CKD. Therefore, diabetic retinopathy is useful for prognosticating the clinical course of diabetic kidney disease.

scholarly journals The Effect of HbA1c Variability as a Risk Measure for Microangiopathy in Type 1 Diabetes Mellitus

Diagnostics ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 1151
Author(s):  
Pedro Romero-Aroca ◽  
Raul Navarro-Gil ◽  
Albert Feliu ◽  
Aida Valls ◽  
Antonio Moreno ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Diabetic Retinopathy ◽  
Type 1 Diabetes Mellitus ◽  
Risk Measure ◽  
Case Series ◽  
Multivariate Statistical ◽  
Case Series Study ◽  
Prospective Case Series

Background: To measure the relationship between variability in HbA1c and microalbuminuria (MA) and diabetic retinopathy (DR) in the long term. Methods: A prospective case-series study, was conducted on 366 Type 1 Diabetes Mellitus patients with normoalbuminuria and without diabetic retinopathy at inclusion. The cohort was followed for a period of 12 years. The Cox survival analysis was used for the multivariate statistical study. The effect of variability in microangiopathy (retinopathy and nephropathy) was evaluated by calculating the standard deviation of HbA1c (SD-HbA1c), the coefficient of variation of HbA1c (CV-HbA1c), average real variability (ARV-HbA1c) and variability irrespective of the mean (VIM-HbA1c) adjusted for the other known variables. Results: A total of 106 patients developed diabetic retinopathy (29%) and 73 microalbuminuria (19.9%). Overt diabetic nephropathy, by our definition, affected only five patients (1.36%). Statistical results show that the current age, mean HbA1c, SD-HbA1c and ARV-HbA1c are significant in the development of diabetic retinopathy. Microalbuminuria was significant for current age, mean HbA1c, CV-HbA1c and ARV-HbA1c. Conclusions: By measuring the variability in HbA1c, we can use SD-HbA1c and ARV-HbA1c as possible targets for judging which patients are at risk of developing DR and MA, and CV-HbA1c as the target for severe DR.

scholarly journals Gene expression and DNA methylation analyses suggest that two immune related genes are prognostic factors of colorectal cancer

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Xiao-Liang Xing ◽  
Zhi-Yong Yao ◽  
Chaoqun Xing ◽  
Zhi Huang ◽  
Jing Peng ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Risk Assessment ◽  
Dna Methylation ◽  
Differentially Expressed Genes ◽  
Risk Score ◽  
Immune Cells ◽  
Assessment Model ◽  
Differentially Expressed ◽  
Risk Assessment Model

Abstract Background Colorectal cancer (CRC) is the second most prevalent cancer, as it accounts for approximately 10% of all annually diagnosed cancers. Studies have indicated that DNA methylation is involved in cancer genesis. The purpose of this study was to investigate the relationships among DNA methylation, gene expression and the tumor-immune microenvironment of CRC, and finally, to identify potential key genes related to immune cell infiltration in CRC. Methods In the present study, we used the ChAMP and DESeq2 packages, correlation analyses, and Cox regression analyses to identify immune-related differentially expressed genes (IR-DEGs) that were correlated with aberrant methylation and to construct a risk assessment model. Results Finally, we found that HSPA1A expression and CCRL2 expression were positively and negatively associated with the risk score of CRC, respectively. Patients in the high-risk group were more positively correlated with some types of tumor-infiltrating immune cells, whereas they were negatively correlated with other tumor-infiltrating immune cells. After the patients were regrouped according to the median risk score, we could more effectively distinguish them based on survival outcome, clinicopathological characteristics, specific tumor-immune infiltration status and highly expressed immune-related biomarkers. Conclusion This study suggested that the risk assessment model constructed by pairing immune-related differentially expressed genes correlated with aberrant DNA methylation could predict the outcome of CRC patients and might help to identify those patients who could benefit from antitumor immunotherapy.

scholarly journals Global metabolomic and lipidomic analysis reveals the potential mechanisms of hemolysis effect of Ophiopogonin D and Ophiopogonin D' in vivo

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Huan-Hua Xu ◽  
Zhen-Hong Jiang ◽  
Cong-Shu Huang ◽  
Yu-Ting Sun ◽  
Long-Long Xu ◽  
...  
Keyword(s):  
Chemical Properties ◽  
Principal Component ◽  
Partial Least Square ◽  
Least Square ◽  
Practical Significance ◽  
Plasma Metabolites ◽  
Active Components ◽  
The Difference

Abstract Background OPD and OPD' are the two main active components of Ophiopogon japonicas in Shenmai injection (SMI). Being isomers of each other, they are supposed to have similar pharmacological activities, but the actual situation is complicated. The difference of hemolytic behavior between OPD and OPD' in vivo and in vitro was discovered and reported by our group for the first time. In vitro, only OPD' showed hemolysis reaction, while in vivo, both OPD and OPD' caused hemolysis. In vitro, the primary cause of hemolysis has been confirmed to be related to the difference between physical and chemical properties of OPD and OPD'. In vivo, although there is a possible explanation for this phenomenon, the one is that OPD is bio-transformed into OPD' or its analogues in vivo, the other one is that both OPD and OPD' were metabolized into more activated forms for hemolysis. However, the mechanism of hemolysis in vivo is still unclear, especially the existing literature are still difficult to explain why OPD shows the inconsistent hemolysis behavior in vivo and in vitro. Therefore, the study of hemolysis of OPD and OPD' in vivo is of great practical significance in response to the increase of adverse events of SMI. Methods Aiming at the hemolysis in vivo, this manuscript adopted untargeted metabolomics and lipidomics technology to preliminarily explore the changes of plasma metabolites and lipids of OPD- and OPD'-treated rats. Metabolomics and lipidomics analyses were performed on ultra-high performance liquid chromatography (UPLC) system tandem with different mass spectrometers (MS) and different columns respectively. Multivariate statistical approaches such as principal component analysis (PCA) and orthogonal partial least square-discriminant analysis (OPLS-DA) were applied to screen the differential metabolites and lipids. Results Both OPD and OPD' groups experienced hemolysis, Changes in endogenous differential metabolites and differential lipids, enrichment of differential metabolic pathways, and correlation analysis of differential metabolites and lipids all indicated that the causes of hemolysis by OPD and OPD' were closely related to the interference of phospholipid metabolism. Conclusions This study provided a comprehensive description of metabolomics and lipidomics changes between OPD- and OPD'-treated rats, it would add to the knowledge base of the field, which also provided scientific guidance for the subsequent mechanism research. However, the underlying mechanism require further research.

Stem Cell Therapy for T1 D and T2 D Diabetic patients

2020 ◽  
Vol 11 (10) ◽  
pp. 23-25
Author(s):  
Nandakumar Ravichandran
Keyword(s):  
Diabetic Retinopathy ◽  
Beta Cells ◽  
Chronic Condition ◽  
Major Complication ◽  
Limb Ischemia ◽  
Diabetic Patients ◽  
Insulin Production ◽  
Working Age

Diabetes is a chronic condition that causes several diseases. Type 1 and Type 2 dependent diabetes are shown more concern in today’s world. Type1 dependent patients suffers from inability of the Beta cells to produce insulin whereas Type 2 dependent patients suffers from insufficient insulin production. Diabetic Retinopathy, Nephropathy, Critical Limb Ischemia and impaired glucose tolerance are some of the major risk factors of Diabetes. Diabetic Retinopathy is a major complication of Diabetes causing blindness in working age adults. This article discusses some research methods involved in the generation of Beta cells carried out by certain authors, hypothesis and future works in this field.

scholarly journals Lymphatic Vascular Structures: A New Aspect in Proliferative Diabetic Retinopathy

2018 ◽  
Vol 19 (12) ◽  
pp. 4034 ◽  
Author(s):  
Erika Gucciardo ◽  
Sirpa Loukovaara ◽  
Petri Salven ◽  
Kaisa Lehti
Keyword(s):  
Diabetic Retinopathy ◽  
Ex Vivo ◽  
Tissue Level ◽  
Clinical Samples ◽  
Related Factors ◽  
Disease Etiology ◽  
Working Age ◽  
Vascular Structures ◽  
Underlying Mechanisms ◽  
End Stage

Diabetic retinopathy (DR) is the most common diabetic microvascular complication and major cause of blindness in working-age adults. According to the level of microvascular degeneration and ischemic damage, DR is classified into non-proliferative DR (NPDR), and end-stage, proliferative DR (PDR). Despite advances in the disease etiology and pathogenesis, molecular understanding of end-stage PDR, characterized by ischemia- and inflammation-associated neovascularization and fibrosis, remains incomplete due to the limited availability of ideal clinical samples and experimental research models. Since a great portion of patients do not benefit from current treatments, improved therapies are essential. DR is known to be a complex and multifactorial disease featuring the interplay of microvascular, neurodegenerative, metabolic, genetic/epigenetic, immunological, and inflammation-related factors. Particularly, deeper knowledge on the mechanisms and pathophysiology of most advanced PDR is critical. Lymphatic-like vessel formation coupled with abnormal endothelial differentiation and progenitor cell involvement in the neovascularization associated with PDR are novel recent findings which hold potential for improved DR treatment. Understanding the underlying mechanisms of PDR pathogenesis is therefore crucial. To this goal, multidisciplinary approaches and new ex vivo models have been developed for a more comprehensive molecular, cellular and tissue-level understanding of the disease. This is the first step to gain the needed information on how PDR can be better evaluated, stratified, and treated.

scholarly journals Circulating Biomarkers of Diabetic Retinopathy: An Overview Based on Physiopathology

2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Olga Simó-Servat ◽  
Rafael Simó ◽  
Cristina Hernández
Keyword(s):  
Diabetic Retinopathy ◽  
Therapeutic Strategy ◽  
New Drugs ◽  
Diagnostic Tools ◽  
Diabetic Patients ◽  
Circulating Biomarkers ◽  
Pharmacological Treatments ◽  
Early Stages ◽  
Working Age ◽  
Advanced Stages

Diabetic retinopathy (DR) is the main cause of working-age adult-onset blindness. The currently available treatments for DR are applicable only at advanced stages of the disease and are associated with significant adverse effects. In early stages of DR the only therapeutic strategy that physicians can offer is a tight control of the risk factors for DR. Therefore, new pharmacological treatments for these early stages of the disease are required. In order to develop therapeutic strategies for early stages of DR new diagnostic tools are urgently needed. In this regard, circulating biomarkers could be useful to detect early disease, to identify those diabetic patients most prone to progressive worsening who ought to be followed up more often and who could obtain the most benefit from these therapies, and to monitor the effectiveness of new drugs for DR before more advanced DR stages have been reached. Research of biomarkers for DR has been mainly based on the pathogenic mechanism involved in the development of DR (i.e., AGEs, oxidative stress, endothelial dysfunction, inflammation, and proangiogenic factors). This review focuses on circulating biomarkers at both early and advanced stages that could be relevant for the prediction or detection of DR.

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