Editorial: Neurodegeneration and Neuroprotection in Retinal Disease, Volume II.

Editorial on the Research Topic: Neurodegeneration and Neuroprotection in Retinal Disease, Volume I

Reduced Tyrosine and Serine-632 Phosphorylation of Insulin Receptor Substrate-1 in the Gastrocnemius Muscle of Obese Zucker Rat

Obesity has become a serious health problem in the world, with increased morbidity, mortality, and financial burden on patients and health-care providers. The skeletal muscle is the most extensive tissue, severely affected by a sedentary lifestyle, which leads to obesity and type 2 diabetes. Obesity disrupts insulin signaling in the skeletal muscle, resulting in decreased glucose disposal, a condition known as insulin resistance. Although there is a large body of evidence on obesity-induced insulin resistance in various skeletal muscles, the molecular mechanism of insulin resistance due to a disruption in insulin receptor signaling, specifically in the gastrocnemius skeletal muscle of obese Zucker rats (OZRs), is not fully understood. This study subjected OZRs to a glucose tolerance test (GTT) to analyze insulin sensitivity. In addition, immunoprecipitation and immunoblotting techniques were used to determine the expression and tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) and insulin receptor-β (IRβ), and the activation of serine-632-IRS-1 phosphorylation in the gastrocnemius muscle of Zucker rats. The results show that the GTT in the OZRs was impaired. There was a significant decrease in IRS-1 levels, but no change was observed in IRβ in the gastrocnemius muscle of OZRs, compared to Zucker leans. Obese rats had a higher ratio of tyrosine phosphorylation of IRS-1 and IRβ than lean rats. In obese rats, however, insulin was unable to induce tyrosine phosphorylation. Moreover, insulin increased the phosphorylation of serine 632-IRS-1 in the gastrocnemius muscle of lean rats. However, obese rats had a low basal level of serine-632-IRS-1 and insulin only mildly increased serine phosphorylation in obese rats, compared to those without insulin. Thus, we addressed the altered steps of the insulin receptor signal transduction in the gastrocnemius muscle of OZRs. These findings may contribute to a better understanding of human obesity and type 2 diabetes

D-Ribose-Induced Glycation and Its Attenuation by the Aqueous Extract of <i>Nigella sativa</i> Seeds

Background and Objectives: Glycation and oxidative stress are the major contributing factors responsible for diabetes and its secondary complications. Aminoguanidine, a hydrazine derivative, is the only approved drug that reduces glycation with its known side effects. As a result, research into medicinal plants with antioxidant and antiglycation properties is beneficial in treating diabetes and its consequences. This investigation aimed to examine the efficacy of the aqueous extract of Nigella sativa seeds against the D-ribose-induced glycation system. Materials and Methods: The suppression of α-amylase and α-glucosidase enzymes were used to assess the antidiabetic capacity. UV–Visible, fluorescence, and FTIR spectroscopy were used to characterize the Nigella sativa seed extract and its efficacy in preventing glycation. The inhibition of albumin glycation, fluorescent advanced glycation end products (AGEs) formation, thiol oxidation, and amyloid formation were used to evaluate the extracts’ antiglycation activity. In addition, the extent of glycoxidative DNA damage was analyzed using agarose gel electrophoresis. Results: The IC50 for the extract in the α-amylase and α-glucosidase enzyme inhibition assays were approximately 1.39 ± 0.016 and 1.01 ± 0.022 mg/mL, respectively. Throughout the investigation, it was found that the aqueous extract of Nigella sativa seeds (NSAE) inhibited the level of ketoamine, exerted a considerable drop in fluorescence intensity, and reduced carbonyl production and thiol modification when added to the D-ribose-induced glycation system. In addition, a reduction in the BSA-cross amyloid formation was seen in the Congo red, thioflavin T assay, and electrophoretic techniques. NSAE also exhibited a strong capability for DNA damage protection. Conclusion: It can be concluded that Nigella sativa could be used as a natural antidiabetic, antiglycation treatment and a cost-effective and environmentally friendly source of powerful bioactive chemicals

Enhancing the quality and antioxidant capacity of phycocyanin extracted from Spirulina platensis PCC 7345: A quality-by-design approach

Background and Objectives: Phycocyanin, a water-soluble blue pigment extracted from cyanobacteria, is used in various industries. Research has explored its health benefits like antioxidants and anti-inflammatory properties. However, challenges remain in extracting it efficiently and ensuring stability. This study employs a Quality by Design (QbD) approach to extract Phycocyanin from Spirulina platensis PCC 7345, focusing on Target Product Profiles (TPPs) and Critical Quality Attributes (CQAs). Phycocyanin concentration and purity are the primary CQAs, as they significantly impact product quality. The manuscript investigates the application of the Box-Behnken design to achieve consistentcy extraction of phycocyanin. Methods: Risk assessment via Ishikawa diagrams highlights influential factors. A Box Behnken design evaluates Phycocyanin concentration and purity across 15 formulations. Fourier transform infrared spectroscopy (FTIR) analysis affirms quality, sodium dodecyl sulphate–polyacrylamide gel electrophoresis (SDS-PAGE) validates protein structure, and gas chromatography provides additional insights into molecular composition. Antioxidant potential and enzyme inhibitory activities of the extracted Phycocyanin were analyzed. Results: Phycocyanin exhibits superior antioxidant potential, with half-maximal inhibitory concentration (IC50) values for 2, 2-diphenyl-1-picrylhydrazyl (DPPH), 2, 2′-casino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), and Nitric Oxide Scavenging activity being 40.70 µg/ml, 23.25 µg/ml, and 17.74 µg/ml, respectively. The therapeutic potential of phycocyanin can be confirmed with its effectiveness in inhibition of α-Amylase and α-glucosidase enzymes in a concentration-dependent manner having IC50 values of 72.24 µg/ml and 82.45 µg/ml respectively. Conclusion: The QbD approach ensures quality Phycocyanin extraction. Its antioxidant and enzyme inhibitory properties indicate a promising role in diverse applications in health management

Green Synthesized Silver Nanoparticles of Myrtus communis L (AgMC) Extract Inhibits Cancer Hallmarks via Targeting Aldose Reductase (AR) and Associated Signaling Network

In this current study, we demonstrated the green synthesis and characterization of silver nanoparticles using Myrtus communis L. plant extract (Ag-MC) and its evaluation of anticancer and antimicrobial activities. The green synthesis of (Ag-MC), was assessed by numerous characterization techniques such as ultraviolet-visible spectroscopy (UV-VIS), Fourier-transform infrared spectroscopy (FT-IR), X-ray powder diffraction (XRD) transmission electron microscopy (TEM) and energy dispersive x-ray spectroscopy (EDX). The anti-cancer activity of the green synthesized silver nanoparticles was evaluated by the median inhibitory dose (IC50) on human liver carcinoma cell lines (HepG2). These results suggested that SN-NPs can be used as effective anticancer cell lines, as well as antibacterial and antiseptic agents in the medical field. This study showed that overexpression of aldose reductase (AR) in the human liver carcinoma cell line, HepG2, was down regulated by administration of SN-MC. The down regulation of AR was associated with abrogation of Pl3k/Akt, ERK and NF-kB pathways and the inhibition of cancer hallmarks, however, the target molecule for Ag-MC was not practically established. Thus it is still unknown if the consequences were due to AR inhibition or direct Ag-MC interaction with AR

Diabetes-induced stimulation of the renin-angiotensin system in the rat brain cortex

Cerebrovascular disease is a threat to people with diabetes and hypertension. Diabetes can damage the brain by stimulating the renin-angiotensin system (RAS), leading to neurological deficits and brain strokes. Diabetes-induced components of the RAS, including angiotensin-converting enzyme (ACE), angiotensin-II (Ang-II), and angiotensin type 1 receptor (AT1R), have been linked to various neurological disorders in the brain. In this study, we investigated how diabetes and high blood pressure affected the regulation of these major RAS components in the frontal cortex of the rat brain. We dissected, homogenized, and processed the brain cortex tissues of control, streptozotocin-induced diabetic, spontaneously hypertensive (SHR), and streptozotocin-induced SHR rats for biochemical and Western blot analyses. We found that systolic blood pressure was elevated in SHR rats, but there was no significant difference between SHR and diabetic-SHR rats. In contrast to SHR rats, the heartbeat of diabetic SHR rats was low. Western blot analysis showed that the frontal cortexes of the brain expressed angiotensinogen, AT1R, and MAS receptor. There were no significant differences in angiotensinogen levels across the rat groups. However, the AT1R level was increased in diabetic and hypertensive rats compared to controls, whereas the MAS receptor was downregulated (p < 0.05). These findings suggest that RAS overactivation caused by diabetes may have negative consequences for the brain's cortex, leading to neurodegeneration and cognitive impairment

Angiogenesis regulatory factors in the vitreous from patients with proliferative diabetic retinopathy

We determined the levels of the endogenous angiogenesis inhibitors soluble vascular endothelial growth factor receptor-1 (sVEGFR-1), thrombospondin (TSP)-1 and TSP-2 in the vitreous fluid from patients with proliferative diabetic retinopathy (PDR) and correlated their levels with clinical disease activity and the levels of vascular endothelial growth factor (VEGF). Vitreous samples from 30 PDR and 25 nondiabetic patients were studied by enzyme-linked immunosorbent assay. TSP-1 was not detected. VEGF and TSP-2 levels were significantly higher in PDR with active neovascularization compared with inactive PDR and nondiabetic patients (P < 0.001 for both comparisons). VEGF, sVEGFR-1 and TSP-2 levels were significantly higher in PDR with hemorrhage compared with PDR without hemorrhage and nondiabetic patients (P = 0.0063; 0.0144; <0.001, respectively). VEGF and sVEGFR-1 levels were significantly higher in PDR without traction retinal detachment (TRD) compared with PDR with TRD and nondiabetic patients (P = 0.038; 0.022, respectively). TSP-2 levels were significantly higher in PDR with TRD compared with PDR without TRD and nondiabetic patients (P < 0.001). There was a significant correlation between levels of VEGF and sVEGFR-1 (r = 0.427, P = 0.038). Our findings suggest that upregulation of sVEGFR-1 and TSP-2 may be a protective mechanism against progression of angiogenesis associated with PDR. TSP-2 might be associated with TRD.status: publishe

<em>Loranthus regularis</em> Ameliorates Neurodegenerative Factors in the Diabetic Rat Retina

Diabetic retinopathy remains a primary source of blindness with the growing pandemic of diabetes. Numerous studies have shown that early neurodegeneration caused by elevated oxidative stress may initiate microvascular damage in the diabetic retina during the last few decades. A variety of preventive and treatment strategies using phytochemicals that possess high antioxidants have shown great promise in reducing diabetes-induced neurodegeneration retinal damage. In this investigation, we employed an extract of Loranthus regularis, a traditional medicinal herb which is found to improve diabetes and associated complications in experimental studies. We orally treated STZ-induced diabetic rats with L. regularis and analyzed the neurodegenerative factors in the retina. After treatments, we used Western blotting techniques to analyze the protein content of neurotrophic factors (NGF, BDNF, TrkB), apoptotic factors (cytochrome c, Bcl-2, Bax), and phosphorylation of AKT in the diabetic retina. Additionally, we used ELISA methods to measure the contents of BDNF and the activity of Caspase-3 and biochemical procedures to determine the levels of glutathione and lipid peroxidation (TBARS). Our findings show that L. regularis treatments resulted in a considerable increase in neurotrophic factors and a decrease in apoptotic factors in the diabetic retina. Furthermore, in diabetic retina treated with L. regularis, the level of Bcl-2 protein increased, while the phosphor-AKT signaling improved. As a result, L. regularis may protect against diabetic-induced retinal neuronal damage by increasing neurotrophic support and reducing oxidative stress and apoptosis. Therefore, this study suggests that in diabetic retinopathy, L. regularis could be a potential therapy option for preventing neuronal cell death