Accumulation Of Free Radicals Research Articles

FAdV-4-induced ferroptosis affects fat metabolism in LMH cells

Ferroptosis is a form of controlled cell death that was first described relatively recently and that is dependent on the formation and accumulation of lipid free radicals through an iron-mediated mechanism. A growing body of evidence supports the close relationship between pathogenic infections and ferroptotic cell death, particularly for viral infections. Ferroptosis is also closely tied to the pathogenic development of hepatic steatosis and other forms of liver disease. Fowl adenovirus serotype 4 (FAdV-4) is a hepatotropic aviadenovirus causing hydropericardium syndrome (HPS) that is capable of impacting fat metabolism. However, it remains uncertain as to what role, if any, ferroptotic death plays in the context of FAdV-4 infection. Here, FAdV-4 was found to promote ferroptosis via the p53-SLC7A11-GPX4 axis, while ferrostain-1 was capable of inhibiting this FAdV-4-mediated ferroptotic death through marked reductions in lipid peroxidation. The incidence of FAdV-4-induced fatty liver was also found to be associated with the activation of ferroptotic activity. Together, these results offer novel insights regarding potential approaches to treating HPS.

Potential Impact of SOD2 (rs4880; p.Val16Ala) Variant with the Susceptibility for Childhood Bronchial Asthma.

Oxidative stress is a sophisticated situation that orignates from the accumulation of reactive free radicals within cellular compartments. The antioxidant mechanism of the MnSOD enzyme facilitates the removal of these lethal oxygen species from cellular components. The main goal of this pertained work is to study the contribution of the SOD2 (rs4880; p.Val16Ala) variant to the development of bronchial asthma among children. The study's design was carried out based on a total of 254 participants including 127 asthmatic children (91 atopic and 36 non-atopic) along with 127 unrelated healthy controls. Allelic discrimination analysis was executed using the T-ARMS-PCR protocol. This potential variant conferred a significant association with decreased risk of bronchial asthmatic children under allelic (OR = 0.56, P-value = 0.002), recessive (OR = 0.32, P-value = 0.011), and dominant (OR = 0.51, P-value = 0.040) models. Additionally, atopic and non-atopic asthmatic children indicated a protection against bronchial asthma development under allelic, and dominant models (p-value < 0.05). Our findings suggested that the SOD2*rs4880 variant was correlated with decreased risk of childhood bronchial asthma.

Protective Effects of Astaxanthin on Post-Thaw Sperm Quality in Normozoospermic Men

Fighting against free radical accumulation during the cryopreservation process with the help of exogenous antioxidants has become an effective strategy to augment post-thaw sperm quality. The present study explored the effects of various concentrations of astaxanthin, as a potent antioxidant, on human sperm parameters during the freeze–thaw process. Twenty-five normozoospermic specimens were included in this prospective study. Each sample was divided into five equal parts: fresh group, and frozen–thawed groups including 0, 1, 10, and 50 μM of astaxanthin. The prepared spermatozoa were cryopreserved by rapid freezing technique. Precryopreservation and post-thaw sperm motility parameters, sperm morphology, vitality, DNA fragmentation, reactive oxygen species (ROS) levels, and mitochondrial membrane potential (MMP) were investigated. All sperm parameters after thawing significantly decreased compared to before freezing. Treatment of spermatozoa with 50 μM of astaxanthin significantly increased their total and progressive motility, viability, DNA integrity, and MMP and decreased their intracellular ROS levels compared with the control group. In total, 10 μM of astaxanthin significantly improved total and progressive motility, DNA integrity, MMP, and decreased ROS levels, whereas, in the 1 µM group, there were significant differences only in ROS levels. As a result, we found that astaxanthin can improve sperm quality after freezing/thawing and decrease the detrimental effects of this process on sperm parameters.

Exploring the relationships between physiochemical properties of nanoparticles and cell damage to combat cancer growth using simple periodic table-based descriptors.

A comprehensive knowledge of the physical and chemical properties of nanomaterials (NMs) is necessary to design them effectively for regulated use. Although NMs are utilized in therapeutics, their cytotoxicity has attracted great attention. Nanoscale quantitative structure-property relationship (nano-QSPR) models can help in understanding the relationship between NMs and the biological environment and provide new ways for modeling the structural properties and bio-toxic effects of NMs. The goal of the study is to construct fully validated property-based models to extract relevant features for estimating and influencing the zeta potential and obtaining the toxicity profile regarding cell damage in the treatment of cancer cells. To achieve this, QSPR modeling was first performed with 18 metal oxide (MeOx) NMs to measure their materials properties using periodic table-based descriptors. The features obtained were later applied for zeta potential calculation (imputation for sparse data) for MeOx NMs that lack such information. To further clarify the influence of the zeta potential on cell damage, a QSPR model was developed with 132 MeOx NMs to understand the possible mechanisms of cell damage. The results showed that zeta potential, along with seven other descriptors, had the potential to influence oxidative damage through free radical accumulation, which could lead to changes in the survival rate of cancerous cells. The developed QSPR and quantitative structure-activity relationship models also give hints regarding safer design and toxicity assessment of MeOx NMs.

Total phenolic contents, cytotoxic, free radicals, porcine pancreatic α-amylase, and lipase suppressant activities of Artemisia dracunculus plant from Palestine.

Artemisia dracunculus: L. (A. dracunculus) is a popular vegetable and spice cultivated across many Middle Eastern countries. The herb's aqueous extract has significant folkloric medicinal importance for treating various disorders. Hence, the present investigation aimed to investigate A. dracunculus hydrophilic extract phytochemical constituents and pleiotropic biological potentials, as no previous studies have investigated the antilipase and anti-α-amylase effects of the A. dracunculus plant. Total phenol content and phytochemical screening assays were performed utilizing standard analytical methods. While the α-amylase inhibition, free radical-scavenging, antilipase, and cytotoxic activities were determined using dinitrosalicylic acid (DNSA), DPPH, p-nitrophenyl butyrate (PNPB), and MTS assays, respectively. The standard phytochemical analysis of A. dracunculus aqueous extract shows that this extract contains only a phenolic group. The total phenol content was 0.146 ± 0.012mg GAE/g of the plant dry extract. The A. dracunculus aqueous extract exhibited potent DPPH free radical inhibitory (IC50 dose of 10.71 ± 0.01μg/mL) and anti-lipase activities (IC50 dose of 60.25 ± 0.33μg/mL) compared with Trolox (IC50 = 5.7 ± 0.92μg/mL) and Orlistat (IC50 = 12.3 ± 0.35μg/mL), respectively. However, it showed a weak anti-α-amylase effect (IC50 value > 1,000μg/mL) compared with Acarbose (IC50 = 28.18 ± 1.27μg/mL). A. dracunculus has a cytotoxic effect against the HeLa cancer cell line compared with the chemotherapeutic agent Doxorubicin. The extract has the same percent of inhibition as Doxorubicin (99.9%) at 10mg/mL. Overall, these results pointed out for the first time the importance of considering A. dracunculus effects as a favorite candidate for preventing and treating metabolic disorders. Also, our results confirm the findings of previous reports on the role of A. dracunculus in the management of cancer and disorders resulting from the accumulation of harmful free radicals. On the contrary, the current study concluded that the antidiabetic role of A. dracunculus could be minimal. Further in-depth investigations are urgently warranted to explore the importance of A. dracunculus in pharmaceutical production.

Histochemical Staining and SDS-PAGE Analysis of Blackgram Genotypes Subjected to Temperature Induction Response Technique

The study was conducted at Department of Crop Physiology, Agricultural College, Bapatla in Acharya N.G Ranga Agricultural University. The results of the histo-chemical staining revealed that the genotypes TBG-129, PU-1804 and TBG-104 showed lesser free radical accumulation on the surface of the leaves indicating tolerance to high temperatures. The protein profile as evidenced by SDS page analysis indicated distinct expression of band between 23-30 KDa protein in tolerant genotypes such as TBG-129, PU-1804, LBG-995, PU-31, TBG-104, TBG-141, LBG-1004, LBG-1015 and LBG-996. Moreover, the band between 23-30 KDa was denser in TBG-129 and PU-1804. This expression of protein might be an indicative feature of thermotolerance.

Neurological disorders with general overheating of the body (scientific and literary review)

Based on the understanding of the pathophysiology of heat stroke, it has been suggested that heat stroke can be considered as a form of hyperthermia that is associated with a systemic inflammatory response leading to a syndrome of multiple organ dysfunction in which encephalopathy predominates. Mechanisms of neuronal injury in heat stroke include: cellular effects (damage to membranes, mitochondria, and DNA, stimulation of excitotoxic mechanisms, protein denaturation), local effects (ischemia, inflammatory changes, edema, cytokine release, vascular damage), systemic effects (changes in cerebral blood flow, endotoxemia, translocation of bacteria through a dysfunctional gastrointestinal tract). Neurological manifestations of heat stroke develop in 3 stages according to the time of occurrence: acute, convalescent and late. In the acute stage, cerebral dysfunction prevails. Overheating of the body directly caused polyetiological cerebral dysfunction with deep suppression of consciousness in the acute stage; circulatory shock, hypoxia and cerebral ischemia, excessive accumulation of cytotoxic free radicals and oxidant brain damage developed. During the convalescence stage, cerebral dysfunction gradually decreases. This stage is characterized by transient cerebellar dysfunction. For the late stage, long-term neurological and cardiovascular complications with a constant risk of death are typical. When late stage with permanent neurologic deficits develop, cerebellar dysfunction is the most common symptom. The delayed onset of degeneration and deafferentation suggests that the syndrome is not caused by the primary lesion itself but may be a consequence of postsynaptic hypersensitivity or secondary reorganization of the involved pathways.

Jujubes and Rosuvastatin: Comparison of Two Hypolipidemic Agents in Primary and Secondary Hyperlipidemic and Hypertensive Patients

Biotransformation in human body results accumulation of free radicals (reactive oxygen species or ROS). If patients LDL particles are more than normal in systemic circulation, get interacted with free radicals and form foamy cells; initial stage of coronary artery disease (CAD). Hyperlipidemia may be primary (genetic reason) or secondary which is acquired type of dyslipidemia. Free radicle formation in human body is very much normal phenomenon. Just reducing LDL or raising HDL may prevent interaction of LDL with reactive oxygen species (free radicals), escaping patient to develop CAD. Commonly used drugs in prophylaxis or treatment of dyslipidemia include statins (HMGCo-A reductase inhibitors), niacin, bile resins and fibric acids. There are alternative therapies for dyslipidemia including use of fibers, fruits, and vegetables. In Pakistan there are huge number of fruits and herbs which are getting popularity as hypolipidemic agents. One of the important fruit in Pakistan having hypolipidemic potential is JUJUBES (in urdu called Bair). In this study we have compared hypolipidemic effects of Bair with statin in hyperlipidemic patients. This study was conducted at Begum Jan hospital, Islamabad-Pakistan. Sixty hyperlipidemic patients were selected and divided in two groups. Their lipid profile (LP) was determined in the hospital and blood pressure (BP) was recorded at start of treatment. Group-1 was advised to take 10 mg tablet Rosuvastatin in divided doses, and group-2 was advised to use 500 mg Bair (JUJUBES) in divided times per day for the period of 2 months. RESULTS: after two months therapy their lipid profile and BP was re-determined and analyzed statistically by using SPSS version 22.00.01. It was observed that Rosuvastatin decreased systolic BP and LDL-c highly significantly (p-value &lt; 0.001), while diastolic BP was reduced significantly (p-value &lt;0.01) and HLD-c was increased significantly with p-value &lt;0.01. In group-2 JUJUBES (Bair) reduced systolic BP and LDL-c significantly (p-value &lt;0.01) but no significant changes were observed in diastolic BP and HDL-c in this group. CONCLUSION: It was concluded from the research study that Jujubes reduce LDL-c and systolic BP in hyperlipidemic patients, but lesser than statin group of antihyperlipidemic agents.

Protective role of melatonin in ultraviolet radiation- induced oxidative stress in human skin photoaging

The ultraviolet radiation of the sun that reaches the earth is made up of ultraviolet A (95%) and ultraviolet B (5%). Exposure to ultraviolet radiation (UVR) is the main factor in photoaging. Chronic exposure to sunlight acts as an environmental stressor, leading to oxidative damage or stress. Oxidative damage stimulates the accumulation of free radicals, such as reactive oxygen species (ROS) or reactive nitrogen species (RNS) that are responsible for premature skin aging. Photoaged skin is characterized externally by irregular pigmentation, wrinkles, and reduced skin elasticity, and internally by the breakdown of dermal collagen and elastin. Free radicals can be scavenged and the skin can be protected from further oxidative damage by antioxidants. Melatonin is a hormone produced mainly by the pineal gland, as well as many other organs, including the skin. One of the functions of melatonin is exerted by the antioxidative melatoninergic system to prevent ultraviolet (UV)-induced skin photoaging. The aim of this review was to study the protective effect of melatonin on skin photoaging resulting from UVR exposure. The references were tracked using various databases, such as Google Scholar and PubMed with regard to publications in English for the last 5 years (2019-2023). Melatonin inhibits UVR-induced aging in multiple ways, such as protecting skin cells, binding free radicals, accelerating the activity of antioxidant enzymes, preventing increased mitochondrial membrane permeability, and assisting electron transport efficiency in the mitochondrial respiratory chain. Exogenous application of melatonin is usually by the oral route, but for localized effects on the skin, topical administration is recommended, with consideration of preparations with a better half-life and bioavailability. Understanding the protective antioxidant function of melatonin in UV-induced skin photoaging helps to optimize its application. The protective properties of melatonin against UVR-oxidative stress-induced photoaging will be further explored in this review.

Assessment of variations in the haematological and hepatorenal biomarkers alongside oxidant‐antioxidant imbalance in exotic and indigenous horses infected with Theileria equi

SummaryBackgroundTheileria equi latently infected horses remain under oxidative stress which can be easily determined by evaluating the concerned biomarkers. Until now, very limited data are available regarding study of oxidative stress alongside hepatorenal biomarker alterations in carrier equids.ObjectivesThis study was aimed to investigate oxidative stress and hepato‐renal alterations in respective biomarkers in latently T. equi‐infected exotic and indigenous horses.Study designThe study involved 24 (n = 24) T. equi latently infected horses (11 exotic and 13 indigenous) while 50 horses (n = 50) served as the non‐infected group. Haematological, hepato‐renal and oxidative stress biomarkers analysis was carried out to evaluate the effect of latent T. equi infection on these parameters.ResultsIn the T. equi‐infected exotic horse group, significant decreases in Hb, PCV, TLC and eosinophils were observed in comparison with the T. equi‐infected indigenous horse group. Blood glucose and SOD levels were significantly lower while serum MDA levels were significantly increased in T. equi‐infected horses than the noninfected groups. Higher MDA levels are suggestive of biochemical changes in parasitised erythrocytes making their membrane rigid and liable to erythrolysis. Decreased SOD levels were indicative of a disturbance in anti‐oxidative mechanisms leading to accumulation of free radicals attributing to oxidative injuries to T. equi‐infected erythrocytes.Main limitationsLatently infected animals with very low parasitaemia which are unable to damage host cells may lead to false negative results. Another limitation is the difficulty in ruling out other similar disease‐causing oxidative stresses.ConclusionThese observations indicated that T. equi naturally latently infected exotic horses were more liable to develop a condition in comparison to indigenous infected horses. From the above results, we can conclude that T. equi infection exerts a marked effect on the hepato‐renal biomarkers and significantly affects the key antioxidant defence mechanisms of infected erythrocytes, leading to oxidative damage to the erythrocytes membrane and ultimately its haemolysis.

Bioactive Compounds for Combating Oxidative Stress in Dermatology.

There are extensive studies that confirm the harmful and strong influence of oxidative stress on the skin. The body's response to oxidative stress can vary depending on the type of reactive oxygen species (ROS) or reactive nitrogen species (RNS) and their metabolites, the duration of exposure to oxidative stress and the antioxidant capacity at each tissue level. Numerous skin diseases and pathologies are associated with the excessive production and accumulation of free radicals. title altered Both categories have advantages and disadvantages in terms of skin structures, tolerability, therapeutic performance, ease of application or formulation and economic efficiency. The effect of long-term treatment with antioxidants is evaluated through studies investigating their protective effect and the improvement of some phenomena caused by oxidative stress. This article summarizes the available information on the presence of compounds used in dermatology to combat oxidative stress in the skin. It aims to provide an overview of all the considerations for choosing an antioxidant agent, the topics for further research and the answers sought in order to optimize therapeutic performance.

Accumulation of endogenous free radicals is required to induce titan-like cell formation in Cryptococcus neoformans.

Cryptococcus neoformans is an excellent model to investigate fungal pathogenesis. This yeast can produce "titan cells," which are cells of an abnormally larger size that contribute to the persistence of the yeast in the host. In this work, we have used a new approach to characterize them by identifying drugs that inhibit this process. We have used a repurposing off-patent drug library, combined with an automatic method to image and analyze fungal cell size. In this way, we have identified many compounds that inhibit this transition. Interestingly, several compounds were antioxidants, allowing us to confirm that endogenous ROS and mitochondrial changes are important for titan cell formation. This work provides new evidence of the mechanisms required for titanization. Furthermore, the future characterization of the inhibitory mechanisms of the identified compounds by the scientific community will contribute to better understand the role of titan cells in virulence.

Clinical and pathological features of brain iron metabolism in neurodegerative and demyelinating disorders

The results of many modern studies show the significance of the role of changes in iron metabolism and its increased accumulation in the pathogenesis of neurodegenerative and demyelinating diseases. Determining the role of iron metabolism and the characteristics of its distribution in strategically important areas of the brain in diseases of the nervous system is important from a diagnostic point of view, since it can help determine the rate of disease progression and, accordingly, correction of therapy. The article presents modern literature data describing the main disorders of iron metabolism in the structure of the pathogenesis of neurodegenerative diseases (Alzheimer’s disease and Parkinson’s disease), and demyelinating diseases, in particular, multiple sclerosis. Attention is drawn to the role of changes in iron metabolism in the pathogenesis of the process of regulated cell death, ferroptosis, accompanied by depletion of intracellular glutathione, decreased activity of the enzyme glutathione peroxidase-4 and the subsequent process of lipid peroxidation caused by a decrease in the protective antioxidant system of cells and the accumulation of reactive oxygen species. Attention is drawn to the role of the Fenton reaction in the accumulation of free radicals, the oxidation of iron and, as a consequence, its excessive deposition in brain structures. Information is provided on the features of the pathogenesis of neuronal iron accumulation, modern diagnostic capabilities for assessing iron content in strategically important areas of the brain using various methods, and the possibility of various options for therapeutic treatment of these conditions is considered. Attention is drawn to the patterns of iron distribution in normal brain structures depending on age, as well as in the specified nosologies. Data are presented on the connection between an increase in the amount of iron content in brain cells and the severity of clinical manifestations of diseases. Attention is drawn to the relationship between the progression of disease severity and the increase in metal content in the cells of strategically significant areas of the brain. When writing the article, modern materials and meta-analyses were used, containing the results of a significant number of studies devoted to the problem considered in this review.

Effects of Exposure to Radiofrequency at 2.45 GHz on Structural Changes Associated with Lipid Peroxidation in Prepubertal Rat Testicular Tissue

Objective: The increasing use of electronic devices, accompanied by advancing technologies, has led to heightened exposure to non-ionizing electromagnetic radiation (EMR). This exposure instigates the accumulation of free radicals and oxidative damage in tissues, consequently impacting biological systems. Notably, the testis is among the tissues adversely affected by EMR. Numerous studies have highlighted the pivotal role of the testis in sperm production, emphasizing the potential implications of any damage on the reproductive system. This study aims to assess the levels of lipid peroxidation through histological evaluation in the testicular tissue of prepubertal male rats exposed to electromagnetic radiation at varying electric field intensities within the 2.45 GHz radiofrequency (RF) range. Methods: The experimental group comprises six subdivisions, including a sham control group, as well as groups exposed to varying electric field strengths (EFS) of 0.6 V/m, 1.9 V/m, 5 V/m, 10 V/m, and 15 V/m, respectively. Excluding the sham control group, the remaining subgroups were subjected to a daily 2.45 GHz RF exposure for 1 hour starting immediately after fertilization. This exposure to different electric field intensities continued for 45 days post-birth. Results: The samples obtained from the RF radiation-exposed rats exhibited elevated malondialdehyde (MDA) values and decreased glutathione (GSH) values in the testicular tissue. Furthermore, a comparative analysis between the microwave radiation-exposed group and the control group revealed distinct histological alterations in the testicular tissue. Conclusion: In conclusion, our findings indicate that exposure to microwave radiation at an electric field intensity of 15 V/m can lead to significant histopathological and oxidative parameter changes in Wistar rats. These results underscore the potential effects of such exposure on human health.

Role of glutathione reduction in causation severe complications of coronavirus disease-2019

Abstract Background: Coronavirus is a pandemic disease that emerged in China in 2019 with severe respiratory syndromes in conjunction with organ failure and advanced mortality rate where it has attracted worldwide interest. The pathogenicity of the virus increases by exacerbated oxidative stress that leads to the accumulation of free radicals in the body. Frequently, those free radicals are neutralized by antioxidants, especially glutathione. Objective: Thus, this study aimed to evaluate the role of glutathione in the pathogenicity of the virus alongside certain blood parameters. Materials and Methods: In this study, 90 participants were examined for glutathione levels using a specific enzyme-linked immunosorbent assay (ELISA) kit in addition to the levels of hemoglobin (Hb). Ferritin and vitamin D3 were also measured as they are linked to the level of glutathione in coronavirus disease-2019 (COVID-19). Result: The lowest level of Reduced glutathione in COVID-19 hospitalized patients especially male patients alongside with vitamin D3 and Hb levels. Whereas a significant (P &lt; 0.05) increase in ferritin level was recorded. However, a significant (P &lt; 0.05) increase in ferritin level was recorded. Conclusion: This study showed a significant relationship between glutathione level and disease severity in hospitalized patients with COVID-19, where the depletion of the glutathione level may have a central role in COVID-19 severity and pathophysiology.

Biosynthesis of copper oxide nanoparticles (CuO NPs) using sodium lignosulfonate and evaluation of its cutaneous wound healing properties

Repairing cutaneous wounds imposes a lot of cost on the country every year. Also, cutaneous wounds healing is delayed for various reasons such as the accumulation of free radicals, hospital infections, lack of sufficient moisture, traditional dressings, etc. Therefore, treatment methods need to be reviewed. In recent years, a wide range of copper ointments or silver-releasing compounds have been prepared and used. These ointments have overcome some of the problems associated with copper preparation. In the current work, an environment-friendly a green procedure was described for fabrication of CuO NPs by using sodium lignosulfonate as a capping/stabilizing reagent under alkaline medium. The characterization of prepared CuO NPs@NaLS were analysed using SEM, EdaX, ICP-OES, elemental mapping and TEM data. The FE-SEM and TEM results show that the CuO NPs@NaLS formed as spherical NPs with size of 20–30 nm. According to the elementaling map analysis, the Cu and C were existence with good dispersion that detected by EDX in the composite. In this study, ointments with a concentration of 0.1% were prepared from nanoparticles based on basal ointment (as the main substance that keeps the medicine on the wound) and used as a topical application. In this way, on the second day, angiogenesis (angiogenesis) and the severity of edema and edema, on the fifth day, fibroblasts, and on the tenth, fibrocytes and collagen fibers were examined. According to the present study results, the skin wound area in the rats treated with topical use of NPs was significantly reduced, and in terms of histopathology, it showed more improvement compared to other groups. Overall, the results of this study show that recent nanoparticles can be used as a fast and effective treatment for skin wounds healing.

Synthesis and biological evaluation of gallic acid esters as phagocyte oxidative burst inhibitors

Several degenerative diseases, including cancer, are caused by oxidative stress, which is caused by the overproduction and accumulation of free radicals. The purpose of the study was to synthesize gallic acid (GA or 3,4,5-trihydroxybenzoic acid) esters and evaluate their anti-inflammatory potential through the inhibition of reactive oxygen species (ROS). The compounds methyl gallate (2), sec-butyl gallate (3), ethyl gallate (4), isopropyl gallate (5), 2-methoxyethyl gallate (6), 4-methoxybutyl gallate (7), 2-methylbutyl gallate (8) and pentan-3-yl gallate (9) were synthesized. 1H NMR, MS and IR data are reported for compounds 2-9, and 13C NMR data for compounds 2, 3, 5, and 6. The molecular formulae of compounds 3 and 7-9 were established by HREI-MS spectroscopic data. All the synthesized compounds were tested for their anti-inflammatory and cytotoxic activities by chemiluminescence and MTT cytotoxicity assay respectively. The results revealed the anti-inflammatory potential of compounds 2-8 with an IC50 range between (13.3 – 54.3 µM) as compared to the standard anti-inflammatory drug, Ibuprofen (IC50 = 54.3 ± 9.2 μM). The most potent inhibitors were found to be compound 3 (ROS IC50 = 15.0 ± 6.6 µM) and compound 7 (ROS IC50 = 13.3 ± 0.8 µM). All compounds were found to be non-cytotoxic in the NIH-3T3 fibroblast cell line. Compounds 3, 7- 9 were identified as new compounds.

Non-Excitatory Amino Acids, Melatonin, and Free Radicals: Examining the Role in Stroke and Aging.

The aim of this review is to explore the relationship between melatonin, free radicals, and non-excitatory amino acids, and their role in stroke and aging. Melatonin has garnered significant attention in recent years due to its diverse physiological functions and potential therapeutic benefits by reducing oxidative stress, inflammation, and apoptosis. Melatonin has been found to mitigate ischemic brain damage caused by stroke. By scavenging free radicals and reducing oxidative damage, melatonin may help slow down the aging process and protect against age-related cognitive decline. Additionally, non-excitatory amino acids have been shown to possess neuroprotective properties, including antioxidant and anti-inflammatory in stroke and aging-related conditions. They can attenuate oxidative stress, modulate calcium homeostasis, and inhibit apoptosis, thereby safeguarding neurons against damage induced by stroke and aging processes. The intracellular accumulation of certain non-excitatory amino acids could promote harmful effects during hypoxia-ischemia episodes and thus, the blockade of the amino acid transporters involved in the process could be an alternative therapeutic strategy to reduce ischemic damage. On the other hand, the accumulation of free radicals, specifically mitochondrial reactive oxygen and nitrogen species, accelerates cellular senescence and contributes to age-related decline. Recent research suggests a complex interplay between melatonin, free radicals, and non-excitatory amino acids in stroke and aging. The neuroprotective actions of melatonin and non-excitatory amino acids converge on multiple pathways, including the regulation of calcium homeostasis, modulation of apoptosis, and reduction of inflammation. These mechanisms collectively contribute to the preservation of neuronal integrity and functions, making them promising targets for therapeutic interventions in stroke and age-related disorders.

Recent Advances in Electrospun Nanofiber-Based Strategies for Diabetic Wound Healing Application.

Diabetic ulcers are the second largest complication caused by diabetes mellitus. A great number of factors, including hyperchromic inflammation, susceptible microbial infection, inferior vascularization, the large accumulation of free radicals, and other poor healing-promoting microenvironments hold back the healing process of chronic diabetic ulcer in clinics. With the increasing clinical cases of diabetic ulcers worldwide, the design and development of advanced wound dressings are urgently required to accelerate the treatment of skin wounds caused by diabetic complications. Electrospinning technology has been recognized as a simple, versatile, and cost-reasonable strategy to fabricate dressing materials composed of nanofibers, which possess excellent extracellular matrix (ECM)-mimicking morphology, structure, and biological functions. The electrospinning-based nanofibrous dressings have been widely demonstrated to promote the adhesion, migration, and proliferation of dermal fibroblasts, and further accelerate the wound healing process compared with some other dressing types like traditional cotton gauze and medical sponges, etc. Moreover, the electrospun nanofibers are commonly harvested in the structure of nonwoven-like mats, which possess small pore sizes but high porosity, resulting in great microbial barrier performance as well as excellent moisture and air permeable properties. They also serve as good carriers to load various bioactive agents and/or even living cells, which further impart the electrospinning-based dressings with predetermined biological functions and even multiple functions to significantly improve the healing outcomes of different chronic skin wounds while dramatically shortening the treatment procedure. All these outstanding characteristics have made electrospun nanofibrous dressings one of the most promising dressing candidates for the treatment of chronic diabetic ulcers. This review starts with a brief introduction to diabetic ulcer and the electrospinning process, and then provides a detailed introduction to recent advances in electrospinning-based strategies for the treatment of diabetic wounds. Importantly, the synergetic application of combining electrospinning with bioactive ingredients and/or cell therapy was highlighted. The review also discussed the advantages of hydrogel dressings by using electrospun nanofibers. At the end of the review, the challenge and prospects of electrospinning-based strategies for the treatment of diabetic wounds are discussed in depth.

Exposure to Polystyrene Nanoplastics Led to Learning and Memory Deficits in Zebrafish by Inducing Oxidative Damage and Aggravating Brain Aging.

Nanoplastics (NPs) may pass through the blood-brain barrier, giving rise to serious concerns about their potential toxicity to the brain. In this study, the effects of NPs exposure on learning and memory, the primary cognitive functions of the brain, are assessed in zebrafish with classic T-maze exploration tasks. Additionally, to reveal potential affecting mechanisms, the impacts of NPs exposure on brain aging, oxidative damage, energy provision, and the cell cycle are evaluated. The results demonstrate that NP-exposed zebrafish takes significantly longer for their first entry and spends markedly less time in the reward zone in the T-maze task, indicating the occurrence of learning and memory deficits. Moreover, higher levels of aging markers (β-galactosidase and lipofuscin) are detected in the brains of NP-exposed fish. Along with the accumulation of reactive free radicals, NP-exposed zebrafish suffer significant levels of brain oxidative damage. Furthermore, lower levels of Adenosine triphosphate (ATP) and cyclin-dependent kinase 2 and higher levels of p53 are observed in the brains of NP-exposed zebrafish, suggesting that NPs exposure also results in a shortage of energy supply and an arrestment of the cell cycle. These findings suggest that NPs exposure may pose a severe threat to brain health, which deserves closer attention.