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Objective: To quantify microvascular lesions in a large real-world data (RWD) set, based on single central retinal fundus images of diabetic eyes from different origins, with the aim of validating its use as a precision tool for classifying diabetic retinopathy (DR) severity. Design: Retrospective meta-analysis across multiple fundus image datasets. Sample size: The study analyzed 2445 retinal fundus images from diabetic patients across four diverse RWD international datasets, including populations from Spain, India, China and the US. Intervention: The quantification of specific microvascular lesions: microaneurysms (MAs), hemorrhages (Hmas) and hard exudates (HEs) using advanced automated image analysis techniques on central retinal images to validate reliable metrics for DR severity assessment. The images were pre-classified in the DR severity levels as defined by the International Clinical Diabetic Retinopathy (ICDR) scale. Main Outcome Measures: The primary variables measured were the number of MAs, Hmas, red lesions (RLs) and HEs. These counts were related with DR severity levels using statistical methods to validate the relationship between lesion counts and disease severity. Results: The analysis revealed a robust and statistically significant increase (p < 0.001) in the number of microvascular lesions and the DR severity across all datasets. Tight data distributions were reported for MAs, Hmas and RLs, supporting the reliability of lesion quantification for accurately assessing DR severity. HEs also followed a similar pattern, but with a broader dispersion of data. Data used in this study are consistent with the definition of the DR severity levels established by the ICDR guidelines. Conclusions: The statistically significant increase in the number of microvascular lesions across DR severity validate the use of lesion quantification in a single central retinal field as a key biomarker for disease classification and assessment. This quantification method demonstrates an improvement over traditional assessment scales, providing a quantitative microvascular metric that enhances the precision of disease classification and patient monitoring. The inclusion of a numerical component allows for the detection of subtle variations within the same severity level, offering a deeper understanding of disease progression. The consistency of results across diverse datasets not only confirms the method's reliability but also its applicability in a global healthcare setting. [ABSTRACT FROM AUTHOR]

Objective: To quantify microvascular lesions in a large real-world data (RWD) set, based on single central retinal fundus images of diabetic eyes from different origins, with the aim of validating its use as a precision tool for classifying diabetic retinopathy (DR) severity. Design: Retrospective meta-analysis across multiple fundus image datasets. Sample size: The study analyzed 2445 retinal fundus images from diabetic patients across four diverse RWD international datasets, including populations from Spain, India, China and the US. Intervention: The quantification of specific microvascular lesions: microaneurysms (MAs), hemorrhages (Hmas) and hard exudates (HEs) using advanced automated image analysis techniques on central retinal images to validate reliable metrics for DR severity assessment. The images were pre-classified in the DR severity levels as defined by the International Clinical Diabetic Retinopathy (ICDR) scale. Main Outcome Measures: The primary variables measured were the number of MAs, Hmas, red lesions (RLs) and HEs. These counts were related with DR severity levels using statistical methods to validate the relationship between lesion counts and disease severity. Results: The analysis revealed a robust and statistically significant increase (p < 0.001) in the number of microvascular lesions and the DR severity across all datasets. Tight data distributions were reported for MAs, Hmas and RLs, supporting the reliability of lesion quantification for accurately assessing DR severity. HEs also followed a similar pattern, but with a broader dispersion of data. Data used in this study are consistent with the definition of the DR severity levels established by the ICDR guidelines. Conclusions: The statistically significant increase in the number of microvascular lesions across DR severity validate the use of lesion quantification in a single central retinal field as a key biomarker for disease classification and assessment. This quantification method demonstrates an improvement over traditional assessment scales, providing a quantitative microvascular metric that enhances the precision of disease classification and patient monitoring. The inclusion of a numerical component allows for the detection of subtle variations within the same severity level, offering a deeper understanding of disease progression. The consistency of results across diverse datasets not only confirms the method’s reliability but also its applicability in a global healthcare setting.

A novel diagnostic method has been developed for microvascular lesions using time constants obtained from the peripheral Windkessel model (WK model). Since the time constant of the WK model reflects changes in resistance and vascular elasticity due to a decrease in the internal vessel diameter, an increase in surface roughness of intima, andan increase in bloodviscosity, it was proposedto use it as an indicator for vascular evaluation. For noninvasive andeasy measurement of the time constant, it is necessary to calculate from the frequency components of the arterial pressure pulse andphalangeal volume pulse. Therefore, it is necessary to establish each pulse wave measurement methodandto consider the optimal combination. The fingertip photoplethysmograph was usedbecause it is saidto be proportional to the volume pulse of the fingertip. Owing to the difficulty of using the conventional air-conduction method for measuring the arterial pressure pulse, reflection photo and cuff pressure methods were considered. The probability of obtaining time constants and the fluctuation rate were compared across the three methods. The results demonstrated the superiority of the air-conduction methodover the other two. The air-conduction methodwas consideredto produce a waveform proportional to the arterial bloodpressure pulse wave. The best pulse wave measurement methodfor measuring peripheral time constants were the air-conduction methodfor arterial pressure pulse andthe transmission photo methodfor fingertip volume pulse. [ABSTRACT FROM AUTHOR]

Objective: To investigate the relationship between microvascular lesions and serum metabolic parameters in patients with type 2 diabetes mellitus(T2DM). Methods: Selected 96 patients with T2DMin our hospital from July 2015 to July 2016, According to the presence of microvascular lesions were divided into observation group (n=43, with microvascular lesions)and control group(n=53, without microvascular lesions). Detected the levels of triacylglycerol(TG), total cholesterol(TC), high density lipoprotein(HDL), low density lipoprotein (LDL), fasting blood glucose(FBG), glycosylated hemoglobin(HbA1C), homocysteine(Hcy)and serum cystatin C(CysC) and vascular endothelial growth factor (VEGF). Logistic regression analysis was used to analyze the risk factors of microvascular lesions. Results: Course of disease, smoking rate in observation group was higher than the control group, the difference was statistically significant (P<0.05); The levels of TG, LDL, HbA1C, CysC, Hcy, VEGF were higher than the control group, the differences were statistically significant(P<0.05), but the TC and HDL levels in two groups had no significant difference(P>0.05); Logistic regression analysis showed that the course of disease, CysC, Hcy, VEGF were the risk factors for microvascular lesions (OR=1.975, 3.643, 4.054, 4.214, P<0.05). Conclusion: CysC, Hcy, VEGF are the risk factors of the microvascular lesions, detecting these indexes is helpful to diagnosis and treatment of early T2DMwith microvascular lesions. [ABSTRACT FROM AUTHOR]

The prognosis of patients with microvascular lesions remains poor because vascular remodeling eventually obliterates the lumen. Here we have focused our efforts on vessel dysfunction in two different organs, the lung and brain. Despite tremendous progress in understanding the importance of blood vessel integrity, gaps remain in our knowledge of the underlying molecular factors contributing to vessel injury, including microvascular lesions. Most of the ongoing research on these lesions have focused on oxidative stress but have not found major molecular targets for the discovery of new treatment or early diagnosis. Herein, we have focused on elucidating the molecular mechanism(s) based on two new emerging molecules NRF1 and ID3, and how they may contribute to microvascular lesions in the lung and brain. Redox sensitive transcriptional activation of target genes depends on not only NRF1, but the recruitment of co-activators such as ID3 to the target gene promoter. Our review highlights the fact that targeting NRF1 and ID3 could be a promising therapeutic approach as they are major players in influencing cell growth, cell repair, senescence, and apoptotic cell death which contribute to vascular lesions. Knowledge about the molecular biology of these processes will be relevant for future therapeutic approaches to not only PAH but cerebral angiopathy and other vascular disorders. Therapies targeting transcription regulators NRF1 or ID3 have the potential for vascular disease-modification because they will address the root causes such as genomic instability and epigenetic changes in vascular lesions. We hope that our findings will serve as a stimulus for further research towards an effective treatment of microvascular lesions. • Knowledge of how emerging transcription regulators NRF1 and ID3 may contribute to microvascular lesions. • Bioinformatic analysis of the interaction between NRF1 and ID3 • Potential of NRF1 and ID3 redox sensitive transcription regulators as therapeutic targets of vascular remodeling [ABSTRACT FROM AUTHOR]

• Cisplatin (CP) induced acute kidney injury (AKI) in rat-model. • AKI was indicated via biochemical and histological alterations in renal tissue. • Melamine, Vit E and Ozone rescued oxidative stress and kidney damage markers. • Melamine, Vit E and Ozone depressed inflammatory state and renal tissue lesions. • A combination of these medications is expected to support cisplatin-induced damage in cancer patients. Cisplatin (CP) is an anticancer medication that is commonly used to treat solid tumors. Its use is, however, dose-restricted due to nephrotoxicity. We planned to compare the nephroprotective effects of three major compounds, including melatonin (MN), Ozone, or vitamin E, against the CP-induced renal damage in rats. CP was given once intraperitoneally (10 mg/kg,) eliciting acute kidney injury as assured by several adverse histological changes; glomerulopathy, tubulopathy, and vasculopathy, an inflammatory response including elevated TNF-α, IL-6, and IL-1β. Furthermore, biochemical alterations including, elevated plasma levels of urea, uric acid, creatinine, phosphorous, decreased plasma calcium levels, and gene expression abnormalities; upregulation of N -acetyl-β-d-glucosaminidase (NAG) and Transforming growth factor-β1 (TGF-β1), downregulation of CAT and SOD. Concurrent supplementation with either MN (10 mg/kg per os) or Ozone (1.1 mg/kg ip) and Vit E given by oral gavage (1 g/kg) for five consecutive days prior to CP injection and five days afterward displayed variable significant nephroprotective effects by mitigating the pro-inflammatory secretion, augmenting antioxidant competence, and modulating the gene expression in the renal tissue. The obtained biochemical, histological, and gene expression data suggested that MN had foremost rescue effects followed by Ozone then Vit E. MN's ameliorative effect was augmented in many indices including TNF-α, IL-6 , IL1-β, uric acid, creatinine, sNGAL and GGT, more than observed in Ozone, and Vit E therapy. A combination of these medications is expected to be more useful in relieving the damaging renal effects of CP given to cancer patients, pending further toxicological and pharmacological research. [ABSTRACT FROM AUTHOR]

Diabetic retinopathy (DR) is one of the most common complications of diabetes mellitus and is characterized by degeneration of retinal neurons and neoangiogenesis, causing a severe threat to vision. Nowadays, the principal treatment options for DR are laser photocoagulation, vitreoretinal surgery, or intravitreal injection of drugs targeting vascular endothelial growth factor. However, these treatments only act at advanced stages of DR, have short term efficacy, and cause side effects. Treatment with nutraceuticals (foods providing medical or health benefits) at early stages of DR may represent a reasonable alternative to act upstream of the disease, preventing its progression. In particular, in vitro and in vivo studies have revealed that a variety of nutraceuticals have significant antioxidant and anti-inflammatory properties that may inhibit the early diabetes-driven molecular mechanisms that induce DR, reducing both the neural and vascular damage typical of DR. Although most studies are limited to animal models and there is the problem of low bioavailability for many nutraceuticals, the use of these compounds may represent a natural alternative method to standard DR treatments. [ABSTRACT FROM AUTHOR]

Background: Fabry disease is an X-linked lysosomal storage disorder and shows globotriosylceramide (Gb3) accumulation in multiple organs, resulting from a deficiency of α-galactosidase. In patients with Fabry disease, cardiovascular disease occurs at an early age. Previous studies have shown that serum levels of high-density lipoprotein-cholesterol (HDL-C) increase in this disease, yet its clinical significance for cardiovascular disease remains unclear., Methods and results: In order to determine why the serum HDL-cholesterol is high in various cardiovascular diseases of Fabry disease patients, we evaluated the serum lipid profiles, ocular vascular lesions, and levels of serum vascular endothelial growth factor (VEGF) and intercellular adhesion molecule-1 in 69 patients with Fabry disease diagnosed by genetic examination. The serum HDL-C/total cholesterol (T-Chol) ratio was significantly high, especially in male patients (41.5±1.7%) regardless of body mass index. Ocular vascular lesions were more likely to occur in female patients with a high HDL-C/T-Chol ratio compared with most male patients. Female patients with a high HDL-C/T-Chol ratio also presented a high serum VEGF level, suggesting that vascular endothelium dysfunction and arteriosclerotic changes progress more severely than in patients with a normal HDL-C/T-Chol ratio. In most patients, enzyme replacement therapy improved serum Gb3 and lyso-Gb3 levels, but these Gb3 and lyso-Gb3 still remained higher than in healthy controls, which appears to result in continuous vascular arteriosclerotic changes., Conclusions: We concluded that increased low-density lipoprotein-cholesterol uptake to the vascular wall caused by endothelial dysfunction is likely to contribute to the high HDL-C/T-Chol ratio observed in Fabry disease patients.