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Oxidative stress-related ocular surface epithelial damage can be initiated by ambient oxygen, UV radiation, and chemical burns. The oxidative damage to cornea can lead to inflammation and even vision loss. Lingzhi (Ganoderma lucidum) is a Chinese herbal drug and has been shown to prevent chronic diseases in clinical practices and has been proven to possess anti-oxidative and anti-inflammatory properties. In the study, we prepared poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) as a sustained drug release system of Lingzhi (LZH) to improve bioavailability. The particle size of developed NPs containing LZH (LZH-NPs) was ~184 nm with narrow size distribution. The results of cellular uptake revealed that using NPs as a drug delivery system could significantly increases the intracellular retention time. The results of the cell viability and chemiluminescence assay revealed that 5 μg/ml of LZH-NPs might be the threshold concentration for cultivation of corneal epithelial cells. After treating LZH-NPs in oxidative damaged cells, the results showed that the inflammation-related gene expression and DNA fragmentation level were both significantly decreased. Post-treatment of LZH-NPs in damaged corneal epithelial cells could increase the cell survival rate. In the rabbit corneal alkali burn model, topical instillation of LZH-NPs could promote corneal wound healing and decrease the inflammation. These results suggest that LZH-NPs may have the potential to treat ocular surface diseases caused by oxidative stress., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Aging is considered as a primary risk factor in the development of osteoarthritis (OA) which associated with mitochondrial dysfunction and oxidative stress. CDGSH iron sulfur domain 2 (Cisd2) deficiency causes mitochondrial dysfunction and drive premature aging. In the present study, thermosensitive chitosan-gelatin based hydrogel containing glutathione was developed as injectable drug delivery system for administration by minimal invasive surgery for the treatment of OA. Cisd2 deficiency (Cisd2 -/- ) mouse induced pluripotent stem cells-derived chondrocytes were established and characterized. The results suggested that 100μM of glutathione may be an optimal concentration to treat Cisd2 -/- chondrocytes without cytotoxicity. The developed hydrogel showed sustained release profile of the glutathione and could decrease the reactive oxygen species level. Post-treatment of glutathione-loaded hydrogel could rescue Cisd2 -/- chondrocytes from oxidative damage via increasing catalase activity, down-regulation of inflammation, and decreasing apoptosis. These results suggest that thermosensitive glutathione-loaded hydrogel may be a potential antioxidant therapeutic strategy for treating Cisd2 -/- chondrocytes in the near future., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Coronary artery disease (CAD) is the primary critical cardiovascular event. Endothelial cell and monocyte dysfunction with subsequent extravagant inflammation are the main causes of vessel damage in CAD. Thus, strategies that repress cell death and manage unsuitable pro-inflammatory responses in CAD are potential therapeutic strategies for improving the clinical prognosis of patients with CAD. SIRT1 (Sirtuin 1) plays an important role in regulating cellular physiological processes. SIRT1 is also thought to protect the cardiovascular system by means of its antioxidant, anti-inflammation and anti-apoptosis activities. In the present study, we found that the SIRT1 expression levels were repressed and the acetylated p53 expression levels were enhanced in the monocytes of patients with CAD. LOX-1/oxidative stress was also up-regulated in the monocytes of patients with CAD, thereby increasing pro-apoptotic events and pro-inflammatory responses. We also demonstrated that monocytes from CAD patients caused endothelial adhesion molecule activation and the adherence of monocytes and endothelial cells. Our findings may explain why CAD patients remain at an increased risk of long-term recurrent ischemic events and provide new knowledge regarding the management of clinical CAD patients., (Copyright © 2017 The Author. Published by Elsevier B.V. All rights reserved.)

Atherosclerosis is considered to be a form of chronic inflammation and a disorder of lipid metabolism. Oxidative transformations in the lipid and apolipoprotein B (Apo B) constituent of low density lipoprotein drive the initial step in atherogenesis due to macrophage scavenger receptors identify oxidized LDL (oxLDL) but non-oxidized LDL. The human vascular endothelial cells fact a critical role in vasodilation, provides a nonadhesive surface for circulation, reduces vascular smooth muscle proliferation, inflammation, thrombus formation and platelet aggregation. Assembly of oxLDL contribute to stimulation of endothelial cells with up-regulation of adhesion molecules, increase oxidative stress to the vascular endothelium and inhibition of NO-mediated vasodilation. When adhesion molecules are over-expressed on the surface of endothelial cells under oxLDL stimulation, it will recruit monocytes to the arterial wall. Then adherent monocytes will migrate into the subendothelial space and subsequently differentiate into macrophages. In the subendothelial space, oxLDL will be taken up by macrophages, thereby causing the substantial cholesterol accumulation and the foam cells production.

Aging-related oxidative stress is considered a major risk factor of cardiovascular diseases (CVD) and could be associated with mitochondrial dysfunction and reactive oxygen species (ROS) overproduction. Cisd2 is an outer mitochondrial membrane protein and plays an important role in controlling the lifespan of mammals. Ferulic acid (FA), a natural antioxidant, is able to improve cardiovascular functions and inhibit the pathogenetic CVD process. However, directly administering therapeutics with antioxidant molecules is challenging because of stability and bioavailability issues. In the present study, thermosensitive chitosan-gelatin-based hydrogel containing FA was used to treat Cisd2-deficient (Cisd2(-/-)) cardiomyocytes (CM) derived from induced pluripotent stem cells of Cisd2(-/-) murine under oxidative stress. The results revealed that the developed hydrogel could provide a sustained release of FA and increase the cell viability. Post-treatment of FA-loaded hydrogel effectively decreased the oxidative stress-induced damage in Cisd2(-/-) CM via increasing catalase activity and decreasing endogenous reactive oxygen species (ROS) production. The in vivo biocompatibility of FA-loaded hydrogel was confirmed in subcutaneously injected rabbits and intramyocardially injected Cisd2(-/-) mice. These results suggest that the thermosensitive FA-loaded hydrogel could rescue Cisd2(-/-) CM from oxidative stress-induced damage and may have potential applications in the future treatment of CVD., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Benzalkonium chloride (BAK) is the most commonly-used preservative in topical ophthalmic medications that may cause ocular surface inflammation associated with oxidative stress and dry eye syndrome. Glutathione (GSH) is an antioxidant in human tears and able to decrease the proinflammatory cytokine release from cells and reactive oxygen species (ROS) formation. Carboxymethyl cellulose (CMC), a hydrophilic polymer, is one of most commonly used artificial tears and can promote the corneal epithelial cell adhesion, migration and re-epithelialization. However, most of commercial artificial tears provide only temporary relief of irritation symptoms and show the short-term treatment effects. In the study, 3-aminophenylboronic acid was grafted to CMC for increase of mucoadhesive properties that might increase the precorneal retention time and maintain the effective therapeutic concentration on the ocular surface. CMC was modified with different degree of substitution (DS) and characterized by Fourier transform infrared spectroscopy and nuclear magnetic resonance spectroscopy. Phenylboronic acid (PBA)-grafted CMC hydrogels have interconnected porous structure and shear thinning behavior. Modification of CMC with high DS (H-PBA-CMC) shows the strong bioadhesive force. The optimal concentration of GSH to treat corneal epithelial cells (CECs) was evaluated by cell viability assay. H-PBA-CMC hydrogels could sustained release GSH and decrease the ROS level. H-PBA-CMC hydrogels containing GSH shows the therapeutic effects in BAK-damaged CECs via improvement of inflammation, apoptosis and cell viability. After topical administration of developed hydrogels, there was no ocular irritation in rabbits. These results suggested that PBA-grafted CMC hydrogels containing GSH might have potential applications for treatment of dry eye disease. • Phenylboronic acid-grafted carboxymethyl cellulose hydrogels have been developed. • Developed hydrogels show the shear-thinning and bioadhesive properties. • Developed hydrogels containing glutathione can reduce the damage induced by BAK. [ABSTRACT FROM AUTHOR]

Abstract Elevated intraocular pressure (IOP) in glaucoma is due to impairment of aqueous humor drainage via the uveoscleral or trabecular outflow pathway. Latanoprost reduces IOP by increasing the uveoscleral outflow. Despite its potency, long-term daily application of it may cause undesirable side effects and many require more than one medication for IOP control. Recent studies have suggested that oxidative stress in the trabecular meshwork (TM) play an important role in the pathogenesis of impaired trabecular outflow facility. Curcumin, a natural phenolic compound, possesses anti-oxidant and anti-inflammation properties. In this study, we developed a thermosensitive hydrogel containing latanoprost and curcumin-loaded nanoparticles (CUR-NPs), and evaluated its possible therapeutic effects with cultured human TM cells under oxidative stress. The results demonstrated that 20 μM of CUR-NPs might be the optimal concentration to treat TM cells without causing cytotoxicity. Using the newly developed system, both latanoprost and CUR-NPs displayed a sustained-release profile. Treatment with this hydrogel containing CUR-NPs effectively decreased the oxidative stress-mediated damage in TM cells via decreasing inflammation-related gene expression, mitochondrial reactive oxygen stress (ROS) production and apoptosis level. The in vivo biocompatibility revealed no signs of inflammation or damage after topical application of developed hydrogel in rabbits. These results suggest that this dual-drug delivery system might enhance both trabecular and uveoscleral outflow and is promising to develop into a novel treatment for glaucoma. Graphical abstract Image 1 Highlights • The eye drop formulation for dual drug delivery was developed and characterized. • The developed dual-drug delivery system showed a sustained release profile. • The developed formulation showed the both in-vitro and in-vivo biocompatibility. • The developed formulation decrease the inflammation and apoptosis levels of cells. • The developed formulation rescue TM cells from oxidative damage. [ABSTRACT FROM AUTHOR]

Abstract: Reactive oxygen species-induced oxidative stress is involved in apoptosis of nucleus pulposus (NP) cells that can alter cellular phenotype and accelerate disc degeneration. Ferulic acid (FA) possesses an excellent antioxidant and anti-inflammatory properties. In the study, we developed the thermosensitive FA–gelatin/chitosan/glycerol phosphate (FA–G/C/GP) hydrogel which was applied as a sustained release system of FA to treat NP cells from the damage caused by oxidative stress. The gelation temperature of the FA–G/C/GP hydrogel was 32.17°C. NP cells submitted to oxidative stress promoted by H2O2, and post-treated with FA–G/C/GP exhibited down-regulation of MMP-3 and up-regulation aggrecan and type II collagen in mRNA level. The sulfated-glycosaminoglycan production was increased and the apoptosis was inhibited in the post-treatment group. The results suggest that the thermosensitive FA–G/C/GP hydrogel can treat NP cells from the damage caused by oxidative stress and may apply in minimally invasive surgery for NP regeneration. [Copyright &y& Elsevier]

Abstract: In the degenerative disc, overproduction of reactive oxygen species (ROS) involves in apoptosis and senescence of nucleus pulposus (NP) cells that could accelerate the degenerative process. Ferulic acid (FA) has been reported to have an excellent antioxidant property. In the study, injectable thermosensitive chitosan/gelatin/glycerol phosphate (C/G/GP) hydrogel was applied as a controlled release system for FA delivery. The study was aimed to evaluate possible therapeutic effects of FA-incorporated C/G/GP hydrogel on hydrogen peroxide (H2O2)-induced oxidative stress NP cells. The results showed that the release of FA from C/G/GP hydrogel could decrease the H2O2-induced oxidative stress. Post-treatment of FA-incorporated C/G/GP hydrogel on H2O2-induced oxidative stress NP cells showed up-regulation of Aggrecan and type II collagen and down-regulation of MMP-3 in mRNA level. The results of sulfated-glycosaminoglycans (GAGs) to DNA ratio and alcian blue staining revealed that the GAGs production of H2O2-induced oxidative stress NP cells could reach to normal level. The results of caspase-3 activity and TUNEL staining indicated that FA-incorporated C/G/GP hydrogel decreased the apoptosis of H2O2-induced oxidative stress NP cells. The results suggested that the C/G/GP hydrogel was very suitable for sustained delivery of FA. The FA-incorporated C/G/GP hydrogel would be used to treat the degenerative disc in the early stage before it developed into the latter irreversible stages. [Copyright &y& Elsevier]

Abstract: The degeneration of intervertebral disc (IVD) could be divided into 5 stages. In the first and second stages, there are no significant symptoms but could be traced by MRI or CT-scan. Generally, no aggressive treatment would be processed in the clinics. Reactive oxygen species (ROS) has been overproduced in degenerative IVD that could be associated with apoptosis of NP cells and degradation of ECM. Ferulic acid (FA) has been reported an excellent antioxidant and relatively stable in air. The study was aimed to evaluate the therapeutic effects of FA on hydrogen peroxide-induced oxidative stress NP cells and the potential for early treatment in IVD degeneration. The results showed that 500μM of FA might be the threshold dose to treat NP cells without cytotoxicity. Post-treatment of FA on hydrogen peroxide-induced oxidative stress NP cells significantly up regulated the expression of aggrecan, type II collagen and BMP-7 and down regulated the expression of MMP-3 in mRNA level. Post-treatment of FA on hydrogen peroxide-induced oxidative stress NP cells could restore the production of sulfated-GAGs and inhibit the apoptosis caused by hydrogen peroxide. From the results of the study, FA could be used as a therapeutic agent for NP regeneration in the very near future. [Copyright &y& Elsevier]

In the initial stage of myocardial infarction (MI), cardiomyocyte necrosis activates aninflammatory response and increases the reactive oxygen species (ROS) content. Graphene oxide (GO) possesses potential antioxidant properties and can provide the adequate mechanical support for cell growth. The clinical studies showed that direct injection of Wharton's jelly mesenchymal stem cells (WJ-MSCs) into infarcted areas of myocardium can reduce apoptosis and fibrosis. Gelatin is a natural polymer and can promote cell attachment. Nanoclay laponite with shear-thinning properties can be injected and gelled in-situ without chemical triggers. In the study, injectable GO/laponite/gelatin (GO-LG) hydrogel was developed and characterized. The results of cell viability showed that the optimal concentration of GO flasks (200 to 300 nm) to treat cells was 100 μg/ml. Addition of nanosized GO to the laponite/gelatin (LG) hydrogel could increase the mechanical strength and have both hemocompatibility and cytocompatibility. The release of GO from LG hydrogel could inhibit the H2O2-induced oxidative stress. The GO-LG hydrogel containing WJ-MSCs could decrease inflammation and apoptosis level and increase the cell viability of cardiomyocytes under oxidative stress. We believe that utilizing this newly developed GO-LG hydrogel containing WJ-MSCs may have potential applications in the future for treatment of MI. [Display omitted] ● Graphene oxide/laponite/gelatin hydrogels have been developed and characterized. ● Addition of nanosized GO to the hydrogel could increase the mechanical strength. ● Developed hydrogels show the shear-thinning and recovery behaviors. ● Developed hydrogels containing WJ-MSCs could rescue the damaged cardiomyocytes. ● Developed hydrogels might be applied for the minimally invasive treatment of MI. [ABSTRACT FROM AUTHOR]

[Display omitted] • ROS-responsive dextran-based NPs containing salvianolic acid B have been developed. • Modification of boronic ester with dextran could enhance the thermal stability. • H 2 O 2 -triggered hydrolysis of SAB-NPs was in a biologically accessible range. • Laponite containing SAB-NPs could scavenge ROS and treat oxidative damaged HUVECs. • Developed hydrogels might be applied for the minimally invasive treatment of PAD. Reactive oxygen species (ROS)-induced oxidative stress plays a key role in the peripheral arterial disease (PAD). Salvianolic acid B (SAB) is a natural phenolic compound and possesses antioxidant properties. However, the poor bioavailability of hydrophilic SAB may limit its applications. Boronic ester-based nanoparticles (NPs) as ROS‐responsive carriers can release drug rapidly and selectively at damaged tissue. Dextran, a polysaccharide, has been used to decrease the platelet aggregation in PAD patients. Laponite, a synthetic nanoclay, has been widely used in biomedical applications. In the study, the laponite hydrogels containing ROS-responsive dextran-based NPs was developed as a carrier for SAB delivery. The synthesis processes of boronic ester modified dextran (PHB-DEX) were characterized by Fourier transform infrared spectrophotometer and thermogravimetry analyzer. The PHB-DEX NP was ∼195.3 nm with spherical structure and could be hydrolyzed completely within 9 min under oxidative stress. Optimal concentration of SAB to treat HUVECs was ∼100 μM. The results of scanning electron microscopy demonstrated that SAB-loaded NPs (SAB-NPs) were well dispersed in laponite hydrogels matrix. The rheological behaviors of laponite containing SAB-NPs (LNPs) showed the shear-thinning properties and increase of fluidity when removing shear stress. The LNPs with sustained drug release properties could scavenge ROS and rescue human umbilical vein endothelial cells from oxidative damage via decrease of the inflammatory level (TNF , IL-1α , IL-1β , IL-6 , and MMP-9) and apoptosis. The biocompatibility of the developed hydrogels has been demonstrated in-vivo. The results suggested that the developed LNPs might have potentials for PAD treatment. [ABSTRACT FROM AUTHOR]

Oxidative damage to cornea can be induced by alkaline chemical burn which may cause vision loss or blindness. Recent studies showed that exogenous application of natural antioxidants may be a potential treatment for corneal wound healing. However, low ocular bioavailability and short residence time are the limiting factors of topically administered antioxidants. Ferulic acid (FA) is a natural phenolic compound and an excellent antioxidant. The study was aimed to investigate the effects of FA in corneal epithelial cells (CECs) under oxidative stress and evaluate the feasibility of use the thermosensitive chitosan-based hydrogel containing FA for corneal wound healing. The results demonstrated that post-treatment of FA on CECs could decrease the inflammation-level and apoptosis. In the rabbit corneal alkali burn model, post-treatment FA-loaded hydrogel may promote the corneal wound healing. The results of study suggest that FA-loaded hydrogel may have the potential applications in treating corneal alkali burn. [ABSTRACT FROM AUTHOR]