Reduction Of Oxidative Stress Research Articles

Will melatonin supplementation become a new form of obesity treatment? A review of recent literature.

Background: In 2020, the World Health Organization (WHO) estimated that 650 million adults worldwide are obese, and 2.8 billion individuals struggle with overweight. Obesity is associated with an increased risk of cardiovascular diseases, type 2 diabetes, heart disease, adverse effects on mental health, the development of certain cancers, and other conditions. In recent years, there has been growing interest in the role of melatonin, which has therapeutic potential in the treatment of obesity. Studies suggest that melatonin supplementation may lead to weight reduction and improvement in metabolic parameters, significantly reduce cardiovascular disease risk factors, and enhance insulin sensitivity in obese individuals. Aim of study: This review aims to present the latest scientific findings on the impact of melatonin supplementation on the development of obesity and its complications. We focus primarily on the mechanisms of melatonin's action in the context of obesity, particularly on potential pathways that have not yet been thoroughly explored. Our aim is to provide deeper insights into research on obesity and its prevention. Materials and Methods: Search was conducted using PubMed and Google Scholar databases, utilizing the keywords "obesity," "melatonin," and "weight loss" in various configurations. The review primarily considers studies published after 2016 that are available online. Summary Melatonin supplementation leads to a statistically significant reduction in blood glucose levels and an increase in cellular insulin sensitivity. Its promising properties in the treatment of obesity have been demonstrated through the reduction of oxidative stress, indicating a potential adjunct for weight loss. Based on the cited studies, the beneficial effects of melatonin supplementation on cardiovascular risk factors have been confirmed. Melatonin could be considered as an adjunctive therapy for obese individuals who do not respond to other treatment modalities.

Potential of Sulodexide in the Treatment of Diabetic Retinopathy and Retinal Vein Occlusion.

Retinal vascular diseases, such as diabetic retinopathy or retinal vein occlusion, are common causes of severe vision loss. Central to the pathophysiology of these conditions are endothelial dysfunction, inflammation, capillary leakage, ischemia, and pathological neoangiogenesis. Capillary damage leads to leakage and the development of macular edema, which is associated with vision loss and requires complex treatment. Sulodexide, a glycosaminoglycan composed of heparan sulfate and dermatan sulfate with high oral bioavailability, exhibits several favorable pharmacologic properties, including antithrombotic, anti-inflammatory, and endothelium-protective effects. Additionally, treatment with sulodexide has been associated with the reduction of oxidative stress and decreased expression of angiogenic growth factors, such as vascular endothelial growth factor. This review aims to provide an overview of the pharmacological properties, mechanisms of action, and therapeutic effects of sulodexide. Furthermore, its potential for clinical application in venous and diabetic diseases, such as venous thromboembolism, chronic venous insufficiency, peripheral artery disease, or diabetic nephropathy, is summarized. We also present experimental and clinical studies evaluating the potential of sulodexide in ocular conditions and discuss its therapeutic implications for the treatment of retinal vascular diseases.

Interleukin(IL)-37 attenuates isoproterenol (ISO)-induced cardiac hypertrophy by suppressing JAK2/STAT3-signaling associated inflammation and oxidative stress

BackgroundInflammation and oxidative stress have drawn more and more interest in the realm of cardiovascular disease. In many different disorders, IL-37 acts as an anti-inflammatory and suppressor of inflammation. This study aimed to investigate whether IL-37 could alleviate cardiac hypertrophy by reducing inflammation and oxidative stress. MethodsIn vivo, a cardiac hypertrophy model was induced by 14 d of daily isoproterenol (ISO, 30 mg/kg/d) injection, followed by weeks of treatment with recombinant human IL-37 (1000 ng/animal), administered three times weekly. Assessments concentrated on markers of inflammation and oxidative stress, apoptosis, myocardial disease, and cardiac shape and function. In vitro, neonatal rat cardiomyocytes (NRCMs) were subjected to ISO (10 µM) to establish a cardiomyocytes hypertrophy model. Subsequent IL-37 treatment (100 ng/ml) was applied to determine its cardioprotective efficacy and to elucidate further the underlying mechanisms involved. ResultsSignificant cardioprotective benefits of IL-37 were seen (in vitro as well as in vivo), primarily through the reduction of oxidative stress, inflammation, apoptosis, and heart hypertrophy markers. Furthermore, IL-37 treatment was associated with a decrease in JAK2 and STAT3 phosphorylation. It is interesting to note that WP1066, a JAK2/STAT3 inhibitor, exhibited antioxidant and anti-inflammatory properties comparable to IL-37, as well as synergistic effects when mixed with the latter. ConclusionISO-induced cardiac hypertrophy is lessened by IL-37 through the reduction of oxidative stress and inflammation. Additionally, the effects of IL-37 are closely related to inactivation of the JAK2/STAT3 signaling pathway. It is anticipated that IL-37 will one day be used to treat cardiovascular illnesses such as heart hypertrophy.

Biocatalytic Clusterzyme Patches Restore Lung Function via Immunomodulation and Mitochondria Protection.

Currently, pulmonary complications such as lung infections during the perioperative period are still the main cause of prolonged hospitalization and death in patients with lung injury due to the lack of effective drugs. Clusterzyme, a kind of artificial enzyme with a high enzyme-like activity and safety profile, exhibits good effects on reducing oxidative stress and immunomodulation. Here, we present the functionalized patches that is administered on the lung airways and rescues the injured organ via clusterzymes. The long-term antioxidant capacity of the patches significantly ameliorated lipopolysaccharide-induced lung function impairment with a significant reduction in lung goblet cell metaplasia and oxidative stress. The inflammatory factors such as cytokines interleukin-1β, interleukin-6, and tumor necrosis factor-α levels decreased by 50%, while the mtDNA copy number increased by 50% and ATP production increased by 100%. Mice lung function was significantly improved, suggesting that the patches can rescue lung injury by modulating oxidative stress and immune responses as well as protecting the mitochondria, providing an avenue for effective intervention of lung injury.

The Therapeutic Potential of Theobromine in Obesity: A Comprehensive Review.

Obesity, characterized by chronic low-grade inflammation, is a significant health concern. Phytochemicals found in plants are being explored for therapeutic use, particularly in combating obesity. Among these, theobromine, commonly found in cocoa and chocolate, shows promise. Although not as extensively studied as caffeine, theobromine exhibits positive effects on human health. It improves lipid profiles, aids in asthma treatment, lowers blood pressure, regulates gut microbiota, reduces tumor formation, moderates blood glucose levels, and acts as a neuroprotective agent. Studies demonstrate its anti-obesity effects through mechanisms such as browning of white adipose tissue, activation of brown adipose tissue, anti-inflammatory properties, and reduction of oxidative stress. This study aims to suggest theobromine as a potential therapeutic agent against obesity-related complications.

Emoxypine succinate modulates behavioral and molecular responses in zebrafish model of iron Overload-Induced neuroinflammation via CDK5/GSK3- β and NLRP3 inflammasome pathway

Excessive iron accumulation in the brain plays a significant role in neurodegenerative processes, contributing to the pathogenesis of Alzheimer’s disease (AD). AD, a prominent neurological disorder affecting the central nervous system, is characterized by the accumulation of beta-amyloid (Aβ) and tau phosphorylation. This accumulation leads to the subsequent development of cognitive impairments, particularly in learning and memory functions. This study investigates the neuroprotective effects of emoxypine succinate in a zebrafish model of iron overload-induced neurodegeneration. Iron was administered to the zebrafish for 28 days to induce neurodegeneration. Following induction, Emoxypine succinate was employed as a treatment intervention for 14 days (concentrations of 4 mg/L, 8 mg/L, and 12 mg/L). Following the end of the treatment, behavioral tests (Y maze test, Novel tank test) were conducted on the zebrafish, and the biochemical (MDA, Catalase, SOD, GSH) and molecular parameters (AchE, Iron levels, IL-1β, TNF-α, CDK-5, GSK-3β, and NLRP3) of the zebrafish brain were also assessed. In the novel tank test, emoxypine succinate-treated groups exhibited significantly increased time in the upper zone (p < 0.001), higher distance travelled (p < 0.001), and shorter latency to the top (p < 0.001) compared to the negative control. Similarly, the Y-maze test revealed improved time in the novel arm (p < 0.001) and total distance travelled (p < 0.001) in treated groups versus the negative control. Assessment of oxidative stress parameters demonstrated significant reductions in oxidative stress in emoxypine succinate-treated groups. Furthermore, AChE activity decreased significantly (p < 0.001), and brain iron levels decreased substantially (p < 0.001) in treated groups, indicating positive therapeutic outcomes. Molecular analysis showed a significant reduction in pro-inflammatory markers like IL-1β, TNF-α, CDK-5, GSK-3β, and NLRP3 (p < 0.001). This comprehensive study highlights the potential efficacy of emoxypine succinate in mitigating neurodegeneration associated with iron dysregulation.

Serum-Free Media Formulation Using Marine Microalgae Extracts and Growth Factor Cocktails for Madin-Darby Canine Kidney and Vero Cell Cultures.

The development of serum-free media (SFM) is critical to advance cell culture techniques used in viral vaccine production and address the ethical concerns and contamination risks associated with fetal bovine serum (FBS). This study evaluated the effects of marine microalgal extracts and growth factor cocktails on the activity of Madin-Darby canine kidney (MDCK) and Vero cells. Five marine microalgal species were used: Spirulina platensis (SP), Dunaliella salina (DS), Haematococcus pluvialis (HP), Nannochloropsis salina (NS), and Tetraselmis sp. (TS). DS and SP extracts significantly increased the proliferation rate of both MDCK and Vero cells. DS had a proliferation rate of 149.56% and 195.50% in MDCK and Vero cells, respectively, compared with that in serum-free medium (SFM). Notably, DS and SP extracts significantly increased superoxide dismutase (SOD) activity, which was 118.61% in MDCK cells and 130.08% in Vero cells for DS, and 108.72% in MDCK cells and 125.63% in Vero cells for SP, indicating a reduction in intracellular oxidative stress. Marine microalgal extracts, especially DS and SP, are feasible alternatives to FBS in cell culture as they promote cell proliferation, ensure safety, and supply essential nutrients while reducing oxidative stress.

The protective effects of Acorus calamus L. rhizome extracts against rheumatoid arthritis-associated dyslipidemia, oxidative stress, and liver injury in rats

ABSTRACT Rheumatoid arthritis (RA) is associated with comorbidities like dyslipidemia and liver damage. Acorus calamus L. is commonly used to treat inflammatory and hepatorenal ailments. Herein, we assessed the hypolipidemic and hepatoprotective activities of A. calamus rhizome extracts in adjuvant-induced arthritis (AIA) in rats. A. calamus rhizome’s methanol (AME) and n-hexane (AHE) extracts were prepared. In vivo, fifty-four female Wistar rats were allocated into nine groups (n = 6). The AIA was induced by injecting Complete Freund’s adjuvant (100 µL, s.c.) into the rat’s right hind paw. After AIA induction, animals were orally treated with meloxicam (MEL; 3 mg/kg) and graded doses (125, 250, and 500 mg/kg) of AME and AHE for 28 consecutive days. Results showed that both plant extracts dose-dependently restored the body weight and liver index of arthritic rats. Each plant extract significantly (p < 0.05) attenuated hyperlipidemia and atherogenicity in arthritic rats. They also normalized the liver function markers and protein concentrations along with the reduction in hepatic oxidative stress. Histopathological examination of the liver supported the biochemical findings. However, AME exhibited better pharmacological activities than AHE. Our findings conclude that A. calamus rhizome could be used to treat dyslipidemia and liver injury in inflammatory conditions like RA.

Experimental study of radioprotective properties of lithium pyruvate in vitro

Radiotoxicity is a serious problem for patients undergoing radiotherapy, so the search for new radioprotective drugs to mitigate its effects is highly relevant. Radioprotectors should have a number of properties, including direct antioxidant action, reduction of oxidative stress, ability to induce DNA repair or inhibit apoptosis, and at the same time not cause their own side effects. Antioxidants based on lithium salts look promising in terms of their properties. The aim of study was to study the radioprotective properties of lithium pyruvate in vitro. Material and Methods. Relatively radiosensitive blood mononuclear cells and relatively radioresistant fibroblasts of 3T3L1 line were used as biomodels for x-ray exposure. Cells were incubated and irradiated in 96-well plates. Lithium pyruvate was used at a final concentration of 1.2 mM. Cells were irradiated at a dose rate of 15 mGy/s in the absorbed-dose range from 0 to 5 Gy using an x-ray unit (anode voltage: 160 kV, average current: 3.5 mA). Cell viability was assessed by MTT test and resazurin test. The evaluation of cell death variants and the level of oxidative stress were determined by cytofluorimetric method. Results. The cytoprotective effect of lithium pyruvate was established. Cytoprotection was manifested in the increased cell survival and decreased oxidative stress level under lithium pyruvate after x-ray in a wide range of absorbed doses. Relatively high efficiency was shown in relation to blood mononuclear cells with an increase in the viable fraction by 5–7 % and a decrease in oxidative stress level during irradiation in the range of 1.0–3.0 Gy. Apoptosis was found to be the main mechanism of cell death after irradiation. Lithium pyruvate reduced the level of apoptosis in cell population under irradiation and chemically induced oxidative stress. Conclusion. Radioprotective effect of lithium pyruvate under x-ray irradiation in vitro has been shown. Reduction of oxidative stress under the action of pyruvate provides a pathogenetic basis for the potential use of this compound as a radioprotector, which requires further studies on in vivo models.

Cardioprotective Effects of Phlorizin on Hyperlipidemia-induced Myocardial Injury: Involvement of Suppression in Pyroptosis via Regulating HK1/NLRP3/Caspase-1 Signaling Pathway.

Hyperlipidemia (HLP) is a prevalent and intricate condition that plays a pivotal role in impairing heart function. The primary objective of this study was to assess the lipid-lowering and cardioprotective properties of phlorizin (PHZ) and to investigate its potential molecular mechanisms in rats. In this investigation, Sprague-Dawley rats were subjected to a high-fat diet for a period of 28days to induce an HLP model. Subsequently, the rats received oral doses of PHZ or metformin from day 14 to day 28. We assessed various parameters using commercially available kits, including serum lipid deposition, myocardial injury biomarkers, oxidative stress markers, and inflammatory cytokine levels. We also employed electron microscopy to examine myocardial ultrastructural changes and conducted Western blot analyses to assess apoptosis factors and pyroptosis markers. Comparing the PHZ group with the model group, we observed significant improvements in blood lipid deposition and heart injury biomarkers. Furthermore, PHZ demonstrated a clear reduction in myocardial tissue oxidative stress and inflammatory factors, as well as a suppression of cell apoptosis. Subsequent investigations indicated that PHZ treatment led to a decreased inflammatory response and lowered levels of hexokinase 1 (HK1), NOD-like receptor thermal protein domain associated protein 3 (NLRP3), apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), and Caspase-1. In summary, PHZ proved to be an effective remedy for alleviating HLP-induced cardiac damage by reducing blood lipid levels, mitigating oxidative stress, curbing inflammation, and suppressing pyroptosis. The inhibition of pyroptosis by PHZ appears to be linked to the regulation of the HK1/NLRP3/Caspase-1 signaling pathway.

SGLT2 inhibition mitigates transition from acute kidney injury to chronic kidney disease by suppressing ferroptosis

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been shown to be renoprotective in ischemia-reperfusion (I/R) injury, with several proposed mechanisms, though additional mechanisms likely exist. This study investigated the impact of luseogliflozin on kidney fibrosis at 48 h and 1 week post I/R injury in C57BL/6 mice. Luseogliflozin attenuated kidney dysfunction and the acute tubular necrosis score on day 2 post I/R injury, and subsequent fibrosis at 1 week, as determined by Sirius red staining. Metabolomics enrichment analysis of I/R-injured kidneys revealed suppression of the glycolytic system and activation of mitochondrial function under treatment with luseogliflozin. Western blotting showed increased nutrient deprivation signaling with elevated phosphorylated AMP-activated protein kinase and Sirtuin-3 in luseogliflozin-treated kidneys. Luseogliflozin-treated kidneys displayed increased protein levels of carnitine palmitoyl transferase 1α and decreased triglyceride deposition, as determined by oil red O staining, suggesting activated fatty acid oxidation. Luseogliflozin prevented the I/R injury-induced reduction in nuclear factor erythroid 2-related factor 2 activity. Western blotting revealed increased glutathione peroxidase 4 and decreased transferrin receptor protein 1 expression. Immunostaining showed reduced 4-hydroxynonenal and malondialdehyde levels, especially in renal tubules, indicating suppressed ferroptosis. Luseogliflozin may protect the kidney from I/R injury by inhibiting ferroptosis through oxidative stress reduction.

Agonistes des récepteurs GLP-1 dans la maladie d’Alzheimer : Potentiel thérapeutique et mécanismes d’action

Alzheimer's disease (AD) is a debilitating neurodegenerative disorder characterized by progressive cognitive decline and neuronal dysfunction. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), originally developed for the treatment of type 2 diabetes, have demonstrated promising neuroprotective effects. This review aims to evaluate the effects and underlying mechanisms of GLP-1 RAs in the context of AD. A comprehensive search of databases yielded 622 articles, from which studies met the predefined inclusion criteria and were subjected to detailed analysis, 29 articles were deemed appropriate for analysis. The results indicate that GLP-1 RAs can significantly reduce amyloid-beta (Aβ) deposition and phosphorylated tau levels in the brains of AD patients. These neuroprotective effects are attributed to multiple synergistic mechanisms, including the enhancement of neuronal survival, reduction of oxidative stress, and attenuation of neuroinflammation. This review underscores the importance of further research to fully elucidate the mechanisms of GLP-1 RAs and their potential as a therapeutic strategy for AD.

House cricket protein hydrolysates alleviate hypertension, vascular dysfunction, and oxidative stress in nitric oxide-deficient hypertensive rats.

Edible insects with high protein content and bioactive peptides with health promotion against chronic disease. Deficiency of nitric oxide (NO) contributes to hypertension, a leading cause of cardiovascular diseases and death worldwide. This study assessed the antihypertensive effects of house cricket protein hydrolysates (HCPH) in NO-deficient hypertensive rats. Male Sprague-Dawley rats (n = 12/group) were hypertensive after the administration of Nω-nitro-L-arginine methyl ester (L-NAME) at a dose of 50 mg/kg body weight (BW)/day in drinking water for 7 weeks. The animals were then treated with HCPH (250 or 500 mg/kg BW/day) or lisinopril (Lis) (1 mg/kg BW/day) for the last 4 weeks of L-NAME administration. Blood pressure (BP), vascular function, and structural changes, endothelial NO synthase (eNOS), and p47phox nicotinamide adenine dinucleotide phosphate (NADPH) oxidase protein expression in aortic tissues, plasma nitrate/nitrite, plasma angiotensin-converting enzyme (ACE) activity, and oxidative stress markers in blood and tissues were evaluated. Induction of hypertension resulted in significantly elevated BP, decreased plasma nitrate/nitrite concentration, abolished vascular function, and increased vascular wall thickness. Overproduction of carotid and mesenteric superoxide, increased plasma, heart, and kidney malondialdehyde, and protein carbonyl levels, and increased plasma ACE activity were observed. Down-expression of eNOS with overexpression of p47phox NADPH oxidase subunit was also found in L-NAME hypertensive rats. Oral treatment with HCPH, particularly at a dose of 500 mg/kg BW/day, significantly alleviated these alterations in a manner comparable to that of Lis. HCPH improved vascular function and exerted antihypertensive effects, mainly due to the improvement of NO bioavailability, reduction of oxidative stress, and inhibition of ACE.

Phytoconstituents-Based Nanotherapeutic Approach for the Effective Management of Joint Inflammatory Condition: Arthritis.

Arthritis, a prevalent inflammatory joint condition, presents challenges for effective therapeutic interventions, with conventional treatments often limited in efficacy and associated with adverse effects. Recent years have witnessed a growing interest in exploring natural compounds, particularly phytoconstituents, renowned for their anti-inflammatory and joint-protective properties. This review aims to illuminate the potential of employing nanotherapeutic approaches with phytoconstituents for enhanced arthritis management. The integration of nanotechnology with phytoconstituents emerges as a promising strategy, addressing limitations in traditional arthritis treatments. Nanocarriers like liposomes and nanoparticles provide a platform for targeted drug delivery, improving the bioavailability of phytoconstituents. Furthermore, the combined effects of phytoconstituents can be leveraged to target multiple pathways in arthritis pathogenesis, including inflammation, oxidative stress, and cartilage degradation. Key phytoconstituents, such as curcumin, resveratrol, and quercetin, exhibit anti-inflammatory and immunomodulatory properties. Nevertheless, their therapeutic potential is often impeded by challenges like poor solubility, stability, and bioavailability. Nanocarriers offer solutions by enhancing pharmacokinetics and enabling sustained release, thereby boosting overall therapeutic efficacy. The review explores the mechanisms underlying the anti-arthritic effects of phytoconstituents and their nanoformulations, including the modulation of pro-inflammatory cytokines, inhibition of matrix metalloproteinases, and reduction of oxidative stress. In summary, the integration of phytoconstituents with nanotechnology presents a promising avenue for developing targeted and effective arthritis therapies. This comprehensive review serves as a valuable resource for researchers, clinicians, and pharmaceutical developers seeking innovative approaches to address the intricate challenges associated with arthritis management.

Chronic Administration of Red Yeast Rice Mitigates Endothelial Dysfunction in Spontaneously Hypertensive Rats by Inhibiting Oxidative Stress and Endothelial Nitric Oxide Synthase Uncoupling.

Hypertension is associated with endothelial dysfunction. An imbalance in the production of Nitric Oxide (NO) and Reactive Oxygen Species (ROS), leading to impaired NO-cyclic Guanosine Monophosphate (cGMP) pathway, contributes to this disorder. Red Yeast Rice (RYR), produced from the fermentation of rice with Monascus purpureus, is a traditional functional food originating from China. Although recognized for its anti-dyslipidemia properties, there has been growing evidence regarding the anti-hypertensive effects of RYR. However, these studies only focused on its direct and short-term effects. This study aims to investigate the vasoprotective effects of chronic oral RYR administration using Spontaneously Hypertensive Rats (SHR). SHR were randomly divided into 3 groups: SHR - Control; SHR - RYR extract (100 mg/kg/day); SHR - lovastatin (10 mg/kg/day). Wistar-Kyoto Rats (WKY) were used as normotensive controls. All animals were treated for 12 weeks by oral gavage. Systolic Blood Pressure (SBP) was measured weekly (tail-cuff method). Vascular reactivity was determined using isolated rat aortic rings in an organ bath. Aortic ROS, NO, tetrahydrobiopterin (BH4), and cGMP levels were evaluated. Administration of RYR attenuated SBP elevation and enhanced endothelium-dependent vasodilation in aortic rings. In addition, RYR decreased ROS production and significantly improved the level of vascular NO, BH4, and cGMP. In an SHR model, treatment with RYR for 12 weeks exerts an SBP lowering effect that can be attributed to improved vascular function via reduction of oxidative stress, decreased endothelial NO Synthase (eNOS) uncoupling and enhanced NO-cGMP pathway.

Effect of umbilical cord mesenchymal stem cell-derived mitochondrial transplantation on ischemia-reperfusion injury in a rat model.

Despite advancements in reconstructive procedures, ischemia-reperfusion (I/R) injury remains a significant challenge in reconstructive surgery, with mitochondrial dysfunction playing a pivotal role. Mitochondrial transplantation has emerged as a promising therapeutic strategy to address this issue. This study aims to evaluate the impact of umbilical cord mesenchymal stem cell-derived mitochondrial transplantation on skin flap I/R models in rats. Twenty male rats underwent I/R injury on skin flaps, with or without mitochondrial transplantation administered via intravenous or subcutaneous routes. Analysis encompassed histopathology, inflammatory, apoptotic, oxidative stress, and hypoxia markers. Results revealed a reduction in inflammation, apoptosis, oxidative stress, and hypoxia in the transplantation group compared to controls. The findings suggest that umbilical cord mesenchymal stem cell-derived mitochondrial transplantation shows promise in enhancing flap viability and attenuating I/R injury, offering valuable insights for improved outcomes in reconstructive surgery. However, further exploration in larger animal models and refinement of delivery methods and dosage are warranted to fully elucidate its clinical translatability.

Myrtenol-Loaded Fatty Acid Nanocarriers Protect Rat Brains Against Ischemia-Reperfusion Injury: Antioxidant and Anti-Inflammatory Effects.

This research investigated the preventive effects of myrtenol (MYR), fatty acid nanocarriers (FANC), and myrtenol-loaded FANC (MYR + FANC) on neurological disturbance, stroke volume, the levels of malondialdehyde (MDA), superoxide dismutase (SOD), and tumor necrosis factor-alpha (TNF-α) in the brain with ischemia-reperfusion injuries induced by middle cerebral artery occlusion (MCAO) in rats. Seventy two Wistar male rats were divided into six main groups. The groups were sham, ischemia-reperfusion group (MACO), MACO-MYR (50 mg/kg), MACO-FANC (50 and 100 mg/kg), and MACO-MYR + FANC (50 mg/kg). Stroke volume, neurological deficit scores, and the brain levels of MDA, SOD, and TNF-α were examined with TTC staining, observation, and ELISA, respectively. Pretreatment with MYR, FANC (100 mg/kg), and MYR + FANC reduced the neurological deficit score and cerebral infarction volume. MYR, FANC (100 mg/kg), and MYR + FANC pretreatment increased and decreased brain SOD and MDA levels compared to MACO group, respectively. The TNF-α level decreased in the MYR + FANC group compared to MCAO and MCAO-MYR groups in the brain. The use of FANC (100 mg/kg), MYR, and MYR + FANC has protective effects against oxidative stress and ischemia-reperfusion injury. FANC probably improve the bioavailability of MYR, as MYR+ FANC had more therapeutic effects on the reduction of ischemia-reperfusion injuries, inflammation, and oxidative stress.

Guanylate cyclase promotes osseointegration by inhibiting oxidative stress and inflammation in aged rats with iron overload.

This study intended to investigate the effect of vericiguat (VIT) on titanium rod osseointegration in aged rats with iron overload, and also explore the role of VIT in osteoblast and osteoclast differentiation. In this study, 60 rats were included in a titanium rod implantation model and underwent subsequent guanylate cyclase treatment. Imaging, histology, and biomechanics were used to evaluate the osseointegration of rats in each group. First, the impact of VIT on bone integration in aged rats with iron overload was investigated. Subsequently, VIT was employed to modulate the differentiation of MC3T3-E1 cells and RAW264.7 cells under conditions of iron overload. Utilizing an OVX rat model, we observed significant alterations in bone mass and osseointegration due to VIT administration in aged rats with iron overload. The observed effects were concomitant with reductions in bone metabolism, oxidative stress, and inflammation. To elucidate whether these effects are associated with osteoclast and osteoblast activity, we conducted in vitro experiments using MC3T3-E1 cells and RAW264.7 cells. Our findings indicate that iron accumulation suppressed the activity of MC3T3-E1 while enhancing RAW264.7 function. Furthermore, iron overload significantly decreased oxidative stress levels; however, these detrimental effects can be mitigated by VIT treatment. Collectively, our data provide compelling evidence that VIT has the potential to reverse the deleterious consequences of iron overload on osseointegration and bone mass during ageing.

A Butyrate-Yielding Dietary Supplement Prevents Acute Alcoholic Liver Injury by Modulating Nrf2-Mediated Hepatic Oxidative Stress and Gut Microbiota.

Alcoholic liver disease (ALD) is a globally prevalent form of liver disease for which there is no effective treatment. Recent studies have found that a significant decrease in butyrate was closely associated with ALD development. Given the low compliance and delivery efficiency associated with oral-route butyrate administration, a highly effective butyrate-yielding dietary supplement, butyrylated high-amylose maize starch (HAMSB), is a good alternative approach. Here, we synthesized HAMSB, evaluated the effect of HAMSB on acute ALD in mice, compared its effect with that of oral administration of butyrate, and further studied the potential mechanism of action. The results showed HAMSB alleviated acute ALD in mice, as evidenced by the inhibition of hepatic-function impairment and the improvement in liver steatosis and lipid metabolism; in these respects, HAMSB supplementation was superior to oral sodium butyrate administration. These improvements can be attributed to the reduction of oxidative stress though the regulation of Nrf2-mediated antioxidant signaling in the liver and the improvement in the composition and function of microbiota in the intestine. In conclusion, HAMSB is a safe and effective dietary supplement for preventing acute ALD that could be useful as a disease-modifying functional food or candidate medicine.

Medical management of vitiligo: a narrative review

Vitiligo is a chronic cutaneous disease presenting with asymptomatic depigmented macular lesions without any signs of inflammation. Since time immemorial, treatment has been sought for this disorder due to the substantial stigma associated with it, more so in patients with skin of color. Vitiligo can be divided into two major clinical types − segmental vitiligo (SV) and non-segmental vitiligo (NSV). The pathophysiological basis for the loss of functional melanocytes resulting in vitiligo includes genetic predisposition, autoimmune mechanisms, and oxidative stress, among others. Thus, combination therapies targeting the autoimmune nature of disease, activation of melanocytes, and reduction of oxidative stress often yield a successful treatment response. There are very few FDA-approved options for vitiligo, and certain recently introduced modalities may modify the way vitiligo is conventionally treated. This review summarizes the conventional as well as the newer medical treatment options for different clinical types of vitiligo.