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Spinal cord injury (SCI) is a prevalent and significant injury to the central nervous system, resulting in severe consequences. This injury is characterized by motor, sensory, and excretory dysfunctions below the affected spinal segment. Transplantation of bone marrow mesenchymal stem cells (BMSCs) has emerged as a potential treatment for SCI. However, the low survival as well as the differentiation rates of BMSCs within the spinal cord microenvironment significantly limit their therapeutic efficiency. Tauroursodeoxycholic acid (TUDCA), an active ingredient found in bear bile, has demonstrated its neuroprotective, antioxidant, and antiapoptotic effects on SCI. Thus, the present study was aimed to study the possible benefits of combining TUDCA with BMSC transplantation using an animal model of SCI. The results showed that TUDCA significantly enhanced BMSC viability and reduced apoptosis (assessed by Annexin V-FITC, TUNEL, Bax, Bcl-2, and Caspase-3) as well as oxidative stress (assessed by ROS, GSH, SOD, and MDA) both in vitro and in vivo. Additionally, TUDCA accelerated tissue regeneration (assessed by HE, Nissl, MAP2, MBP, TUJ1, and GFAP) and improved functional recovery (assessed by BBB score) following BMSC transplantation in SCI. These effects were mediated via the Nrf-2 signaling pathway, as evidenced by the upregulation of Nrf-2, NQO-1, and HO-1 expression levels. Overall, these results indicate that TUDCA could serve as a valuable adjunct to BMSC transplantation therapy for SCI, potentially enhancing its therapeutic efficacy., (© 2024. The Author(s).)

Wedelolactone (WDL) is a coumaryl ether compound extracted from the traditional Chinese medicinal plant, Eclipta prostrata L. It is a natural polyphenol that exhibits a variety of pharmacological activities, such as anti-inflammatory, anti-free radical, and antioxidant activities in the bone, brain, and ovary. However, its effect on embryonic development remains unknown. The present study explored the influence of WDL supplementation of porcine oocytes culture in vitro on embryonic development and the underlying mechanisms and its effect on the levels of Kelch-like ECH-associated protein 1/nuclear factor-erythroid 2-related factor 2/antioxidant response element (Keap1/Nrf2/ARE). The results showed that WDL (2.5 nM) significantly increased the blastocyst formation rate, mitochondrial activity, and proliferation ability while reducing the reactive oxygen species accumulation, apoptosis, and autophagy. These findings suggested that WDL can enhance the growth and development of early porcine embryos to alleviate oxidative stress and autophagy through regulating NRF2 and microtubule-associated protein 1 light chain 3 ( MAP1LC3 ) gene expression levels., Competing Interests: The authors declare that they have no competing interests., (© 2022 Wang et al.)

Background: Tauroursodeoxycholic acid (TUDCA) is a hydrophilic bile acid derivative, which has been demonstrated to have neuroprotective effects in different neurological disease models. However, the effect and underlying mechanism of TUDCA on spinal cord injury (SCI) have not been fully elucidated. This study aims to investigate the protective effects of TUDCA in the SCI mouse model and the related mechanism involved., Methods: The primary cortical neurons were isolated from E16.5 C57BL/6 mouse embryos. To evaluate the effect of TUDCA on axon degeneration induced by oxidative stress in vitro, the cortical neurons were treated with H 2 O 2 with or without TUDCA added and immunostained with Tuj1. Mice were randomly divided into sham, SCI, and SCI+TUDCA groups. SCI model was induced using a pneumatic impact device at T9-T10 level of the vertebra. TUDCA (200 mg/kg) or an equal volume of saline was intragastrically administrated daily post-injury for 14 days., Results: We found that TUDCA attenuated axon degeneration induced by H 2 O 2 treatment and protected primary cortical neurons from oxidative stress in vitro. In vivo, TUDCA treatment significantly reduced tissue injury, oxidative stress, inflammatory response, and apoptosis and promoted axon regeneration and remyelination in the lesion site of the spinal cord of SCI mice. The functional recovery test revealed that TUDCA treatment significantly ameliorated the recovery of limb function., Conclusions: TUDCA treatment can alleviate secondary injury and promote functional recovery by reducing oxidative stress, inflammatory response, and apoptosis induced by primary injury, and promote axon regeneration and remyelination, which could be used as a potential therapy for human SCI recovery., (© 2021. The Author(s).)

Preeclampsia (PE) is a leading cause of perinatal and maternal mortality. Considering that Nesfatin-1 was reported to be downregulated in serum of PE patients, we aimed to explore the functional role of Nesfatin-1 in trophoblast cells. Cell transfection was conducted to overexpress or inhibit Nesfatin-1, and its expression was measured by quantitative PCR. Cell proliferation, migration, and invasion abilities were determined employing CCK-8, flow cytometry, wound-healing, and transwell assays. Immunofluorescence assay was performed to detect E-cadherin and vimentin. ROS, MDA, and SOD levels were measured using their corresponding commercial kits. Western blot was used to identify the expression of vital kinases in PI3K/AKT/mTOR or GSK3β pathway and invasion-related proteins in trophoblast cells. Nesfatin-1 knockdown significantly suppressed proliferation, migration, and invasion and increased cell arrest in G1 phase, as well as downregulated expressions of MMP2/9 in HTR-8/SVneo cells. Besides, Nesfatin-1 knockdown promoted the expression of E-cadherin and reduced the expression of vimentin. Additionally, the levels of ROS, MDA, and SOD were elevated upon Nesfatin-1 knockdown. On the contrary, Nesfatin-1 overexpression exerted the opposite effects. Nesfatin-1 promoted the activation of PI3K/AKT/mTOR or GSK3β pathway, blocking of which reversed the promotive effects on trophoblast invasion and the inhibitory effects on oxidative stress of Nesfatin-1 in HTR-8/SVneo cells. In short, this study revealed that Nesfatin-1 promoted trophoblast cell proliferation, migration, invasion, and EMT and suppressed oxidative stress by activating PI3K/AKT/mTOR and AKT/GSK3β signaling pathway, laying the foundation for the development of therapeutic strategy for PE by targeting Nesfatin-1.

This study aimed to investigate the role and underlying mechanism of miR-135b in high glucose-induced oxidative stress of renal tubular epithelial cells. Here, in vivo experiments found that compared to the control group, miR-135b expression was significantly up-regulated in the diabetes group, whereas BMP7 mRNA and protein levels were down-regulated. In high glucose-treated renal tubular epithelial cells (HK-2) in vitro, oxidative stress was induced, which up-regulated miR-135b expression. In addition, the regulation of miR-135b on BMP7 expression was confirmed in HK-2 cells. Under high glucose conditions, oxidative stress promoted the apoptosis of HK-2 cells through the up-regulation of miR-135b expression. In vivo experiments indicated that interference with miR-135b improved renal function in mice with diabetic nephropathy. In conclusion, these results indicated that the up-regulation of miR-135b expression induced by oxidative stress promotes the apoptosis of HK-2 cells under high glucose conditions., (© 2020 John Wiley & Sons Australia, Ltd.)

Purpose: This study aims to evaluate whether regular lifelong exercise has effects on age-related inflammatory cytokines, oxidative stress, and the skeletal muscle proteome., Methods: Four groups of adult-aged (8-month-old) female Sprague Dawley rats were used: rats for which training was initiated at either 8 (8 M-MICT, moderate-intensity continuous training) or 18 months (18 M-MICT) and sedentary rats aged either 26 (26 M-SED) or 8 months (8M-SED), who served as aging and adult sedentary controls, respectively. Aged skeletal muscles were subjected to proteomic and Kyoto Encyclopedia of Genes and Genomes (KEGG) and immunoblotting analyses., Results: Age-related loss of physical performance and anti-inflammatory steroid levels were lowest in the 8 M-MICT group, while the anti-oxidative activities remained unchanged compared to 18 M-MICT rats. The proteomic analysis demonstrated an amelioration of age-related changes to muscle contraction, focal adhesion signaling, mitochondrial function, apoptosis and regeneration, anti-oxidation, and protein processing in the endoplasmic reticulum in the 8 M-MICT. Additionally, neurotrophin (BDNF) and AKT/FOXO signaling pathways were upregulated in 8 M-MICT rats compared to 26 M-SED., Conclusion: 8 M-MICT exhibited greater beneficial effects in ameliorating age-related inflammation and physical performance loss, compared to 18 M-MICT. The amelioration is potentially related to the upregulation of autophagy activities via BDNF/AKT signaling., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Imperatorin (IMP), a furanocoumarin derivative with many biological properties and pharmacological activities, is widely used as an antibacterial, anti-inflammatory, antiviral, anticancer, cardiovascular and neuroprotective agent. The purpose of this study was to explore the effects of IMP on early embryo development in pigs as well as the potential mechanisms. Our results showed that IMP can enhance the developmental competence of porcine early embryos. Supplementation of in vitro culture medium with 40 μM IMP significantly increased the blastocyst rate and total cell number. At the same time, apoptosis of blastocysts was also significantly decreased in the supplemented group compared with the control group, in accordance with the subsequent results of FAS and CASP3 gene expression analysis. Furthermore, IMP attenuated intracellular reactive oxygen species (ROS) generation, increased fluorescein diacetate (FDA) and glutathione (GSH) levels. Importantly, IMP not only improved the activity of mitochondria but also inhibited the occurrence of autophagy. In addition, pluripotency-related genes (OCT4, NANOG, and SOX2) and a growth and metabolism regulatory gene (mTOR) were upregulated after IMP supplementation on Day 7. These results demonstrate that IMP exerts a beneficial effect on preimplantation embryo development by reducing oxidative stress and autophagy., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Spinal cord injury (SCI) has always been considered to be a devastating problem that results in catastrophic dysfunction, high disability rate, low mortality rate, and huge cost for the patient. Stem cell-based therapy, especially using bone marrow mesenchymal stem cells (BMSCs), is a promising strategy for the treatment of SCI. However, SCI results in low rates of cell survival and a poor microenvironment, which limits the therapeutic efficiency of BMSC transplantation. Coenzyme Q10 (CoQ10) is known as a powerful antioxidant, which inhibits lipid peroxidation and scavenges free radicals, and its combined effect with BMSC transplantation has been shown to have a powerful impact on protecting the vitality of cells, as well as antioxidant and antiapoptotic compounds in SCI. Therefore, we aimed to evaluate whether CoQ10 could decrease oxidative stress against the apoptosis of BMSCs in vitro and explored its molecular mechanisms. Furthermore, we investigated the protective effect of CoQ10 combined with BMSCs transplanted into a SCI model to verify its ability. Our results demonstrate that CoQ10 treatment significantly decreases the expression of the proapoptotic proteins Bax and Caspase-3, as shown through TUNEL-positive staining and the products of oxidative stress (ROS), while increasing the expression of the antiapoptotic protein Bcl-2 and the products of antioxidation, such as glutathione (GSH), against apoptosis and oxidative stress, in a H 2 O 2 -induced model. We also identified consistent results from the CoQ10 treatment of BMSCs transplanted into SCI rats in vivo . Moreover, the Nrf-2 signaling pathway was also investigated in order to detail its molecular mechanism, and the results show that it plays an important role, both in vitro and in vivo . Thus, CoQ10 exerts an antiapoptotic and antioxidant effect, as well as improves the microenvironment in vitro and in vivo . It may also protect BMSCs from oxidative stress and enhance their therapeutic efficiency when transplanted for SCI treatment., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2019 Xing Li et al.)

Radiation therapy toward malignancies is often ineffective owing to radioresistance of cancer cells. On the basis of anti-tumor properties of cordycepin, we examined the effects of cordycepin on sensitizing breast cancer cells toward radiotherapy. Cordycepin administration promoted G2/M arrest and apoptosis of MCF-7 and MDA-MB-231 cells resulting in restraining the proliferation of the cells in vitro and in vivo following irradiation. Mechanistic investigations showed that the breast cancer cells cultured with cordycepin harbored higher levels of intracellular reactive oxygen species (ROS) and incremental numbers of γ-H2AX foci after irradiation exposure. Importantly, cordycepin treatment down-regulated the expression levels of Nuclear factor erythroid 2-related factor (Nrf2) and a series of downstream genes, such as heme oxygenase-1 (HO-1), to enhance ROS in breast cancer cells exposed to irradiation. Together, our observations demonstrate that cordycepin treatment sensitizes breast carcinoma cells toward irradiation via Nrf2/HO-1/ROS axis. Thus, our findings provide novel insights into the function and the underlying mechanism of cordycepin in radiotherapy, and suggest that cordycepin might be employed as a radiosensitizer during radiotherapy toward breast cancer in a pre-clinical setting., (Copyright © 2018. Published by Elsevier Inc.)

Background/aims: Tangeretin (TAN), a major phytochemical in tangerine peels and an important Chinese herb, has multiple biological properties, especially antioxidative and anti-inflammatory effects. However, the mechanisms remain unclear. Based on these findings, the aim of the present study was to assess the antioxidant and anti-inflammatory properties of TAN in bovine type II collagen-induced arthritis rats., Methods: TAN (50 mg/kg) was given orally once daily for 14 days. The effects of treatment were evaluated by biochemical assay (articular elastase, myeloperoxidase, end products of lipid peroxidation [MDA], antioxidant enzyme, such as superoxide dismutase, catalase, glutathione), nitric oxide, and inflammatory cytokines (interleukin-1β [IL-1β], -IL-10, tumor necrosis factor-alpha [TNF-α], interferon-γ [IFN-γ], and prostaglandin E2 [PGE2]). The protective effects of TAN against rheumatoid arthritis (RA) were evident from the decrease in arthritis scoring. Furthermore, the Nrf-2 signaling pathway was assessed to illustrate the molecular mechanism., Results: TAN had therapeutic effects on RA by decreasing the oxidative stress damage and regulating inflammatory cytokine expression, including suppression of the accumulation of MDA products, decreasing the IL-1β, TNF-α, IFN-γ, and PGE2 levels, enhancing the IL-10 and the activity of antioxidant enzymes, which was through upregulating Nrf-2 signaling pathway., Conclusion: TAN might have potential as a therapeutic agent for the treatment of RA., (© 2019 S. Karger AG, Basel.)

Aim: To determine whether 5-aminolevulinic acid-based photodynamic therapy (ALA-PDT) is effective in combating ultraviolet A- (UVA-) induced oxidative photodamage of hairless mice skin in vivo and human epidermal keratinocytes in vitro ., Methods: In in vitro experiments, the human keratinocyte cell line (HaCaT cells) was divided into two groups: the experimental group was treated with ALA-PDT and the control group was left untreated. Then, the experimental group and the control group of cells were exposed to 10 J/m 2 of UVA radiation. ROS, O 2 - species, and MMP were determined by fluorescence microscopy; p53, OGG1, and XPC were determined by Western blot analysis; apoptosis was determined by flow cytometry; and 8-oxo-dG was determined by immunofluorescence. Moreover, HaCaT cells were also treated with ALA-PDT. Then, SOD1 and SOD2 were examined by Western blot analysis. In in vivo experiments, the dorsal skin of hairless mice was treated with ALA-PDT or saline-PDT, and then, they were exposed to 20 J/m 2 UVA light. The compound 8-oxo-dG was detected by immunofluorescence., Conclusion: In human epidermal keratinocytes and hairless mice skin, UVA-induced oxidative damage can be prevented effectively with ALA-PDT pretreatment.

Ultraviolet A (UVA) radiation contributes to skin photoaging. Hesperidin which is a flavanone glycoside found in citrus fruit peels, have been intensively studied for their UVA-protective activity, but its effects and mechanisms on UVA irradiation-induced inflammation and oxidative stress have never been described. Thus, the purpose of this study was to evaluate the effects of hesperidin in skin oxidative stress and inflammation induced by UVA irradiation. In this study, we firstly examined whether hesperidin may exert direct protective effects on the UVA-induced in human keratinocytes (HaCaT) cell injury in vitro. Cell viability was determined by MTT assay. The levels of superoxide dismutase (SOD), malondialdehyde (MDA) and total antioxidative capacity (T-AOC) were measured by using a commercially available kits. Quantitative reverse transcriptase PCR (qRT-PCR) and ELISA were used to determine messenger RNA (mRNA) and protein levels of the tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6. UVA significantly decreased the cell viability (P<0.05). In our study, hesperidin (220μg/ml) significantly reduced UVA-induced oxidative stress and inflammatory response. In conclusion, hesperidin treatment effectively protected HaCaT keratinocytes from these UVA radiation-induced skin injuries, suggesting that the underlying mechanism involves the anti-oxidative and anti-inflammatory capacities, it is possible to be used as a sunscreen agent., (Copyright © 2016. Published by Elsevier B.V.)

Melatonin is involved in defending against oxidative stress caused by various environmental stresses in plants. In this study, the roles of exogenous melatonin in regulating local and systemic defense against photooxidative stress in cucumber (Cucumis sativus) and the involvement of redox signaling were examined. Foliar or rhizospheric treatment with melatonin enhanced tolerance to photooxidative stress in both melatonin-treated leaves and untreated systemic leaves. Increased melatonin levels are capable of increasing glutathione (reduced glutathione [GSH]) redox status. Application of H2 O2 and GSH also induced tolerance to photooxidative stress, while inhibition of H2 O2 accumulation and GSH synthesis compromised melatonin-induced local and systemic tolerance to photooxidative stress. H2 O2 treatment increased the GSH/oxidized glutathione (GSSG) ratio, while inhibition of H2 O2 accumulation prevented a melatonin-induced increase in the GSH/GSSG ratio. Additionally, inhibition of GSH synthesis blocked H2 O2 -induced photooxidative stress tolerance, whereas scavenging or inhibition of H2 O2 production attenuated but did not abolish GSH-induced tolerance to photooxidative stress. These results strongly suggest that exogenous melatonin is capable of inducing both local and systemic defense against photooxidative stress and melatonin-enhanced GSH/GSSG ratio in a H2 O2 -dependent manner is critical in the induction of tolerance., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

MAP/Microtubule affinity-regulating kinase 4 (Mark4) plays an important role in the regulation of microtubule organization, adipogenesis and apoptosis. However, the role of Mark4 plays in oxidative stress and inflammation are poorly understood. In this study, we found Mark4 was induced by high fat diet (HFD) while PPARγ was elevated significantly in mice adipocytes. Further analyses revealed Mark4 impaired mitochondrial oxidative respiration and increased reactive oxygen species (ROS) production. At same time, the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) were greatly reduced. By treating cells with H2O2 and vitamin E (VE), Mark4 accentuated oxidative stress along with increased mRNA level of inflammatory factor interleukin-6 (IL-6) and decreased leptin mRNA. Furthermore, we found PPARγ bind to Mark4 promoter region and inhibited Mark4 expression. We showed PPARγ interacted with Mark4 and inhibited the stimulating effect of Mark4 on oxidative stress and inflammation. Finally, we demonstrated that the IKKα/NF-κB signal pathway was involved in Mark4 induced oxidative stress and inflammation, while PTDC, a special inhibitor of NF-κB signal pathway, reduced oxidative stress and inflammation. Thus, our study indicated that Mark4 was a potential drug target for treating metabolic diseases.

Reactive oxygen species (ROS) are an important factor in the development of skin photodamage after ultraviolet A (UVA) radiation. A flavonoid antioxidant, baicalin, can selectively neutralize super-oxide anion (O(2)(-)) while having no significant effect on (•)OH. Fibroblasts are a key component of skin dermis. In the present study, we investigated the protective effects of baicalin on human skin fibroblasts (HSFs) under UVA induced oxidative stress. Fluorescence microscopy and flow cytometry were used to assay the intracellular O(2)(-), NO, ROS concentrations and the mitochondrial membrane potential. Cell viability was determined using the Cell Counting Kit-8 (CCK-8). The concentrations of cellular MDA, SOD, GSH, T-AOC, and 8-oxo-dG were also measured. Cellular apoptosis was measured by flow cytometry and caspase-3 detection. The results revealed that UVA radiation could cause oxidative stress and apoptosis in HSFs. Interestingly, the use of baicalin after UVA radiation significantly reduced the level of intracellular O(2)(-), NO, and ROS, stabilized the mitochondrial membrane potential, and attenuated production of MDA and 8-oxo-dG. These efficiently enhanced the antioxidative defense system and protected the HSFs from subsequent oxidative stress damage and apoptosis. In other words, baicalin decreased the excessive generation of intracellular ROS and NO, and elevated the cellular antioxidative defense, which eventually mitigate the UVA-induced apoptosis. Based on our results, baicalin may have applications in the treatment of skin photodamage caused by UVA irradiation.

Antioxidant molecules reduce oxidative stress and protect cells from reactive oxygen species (ROS)-mediated cellular damage and probably the development of cancer. We have investigated the contribution of X-box-binding protein (XBP1), a major endoplasmic reticulum stress-linked transcriptional factor, to cellular resistance to oxidative stress. After exposure to hydrogen peroxide (H(2)O(2)) or a strong ROS inducer parthenolide, loss of mitochondrial membrane potential (MMP) and subsequent cell death occurred more extensively in XBP1-deficient cells than wild-type mouse embryonic fibroblast cells, whereas two other anticancer agents induced death similarly in both cells. In XBP1-deficient cells, H(2)O(2) exposure induced more extensive ROS generation and prolonged p38 phosphorylation, and expression of several antioxidant molecules including catalase was lower. Knockdown of XBP1 decreased catalase expression, enhanced ROS generation and MMP loss after H(2)O(2) exposure, but extrinsic catalase supply rescued them. Overexpression of XBP1 recovered catalase expression in XBP1-deficient cells and diminished ROS generation after H(2)O(2) exposure. Mutation analysis of the catalase promoter region suggests a pivotal role of CCAAT boxes, NF-Y-binding sites, for the XBP1-mediated enhancing effect. Taken together, these results indicate a protective role of XBP1 against oxidative stress, and its positive regulation of catalase expression may at least in part account for this function.

Spinal cord injury (SCI) is a prevalent and significant injury to the central nervous system, resulting in severe consequences. This injury is characterized by motor, sensory, and excretory dysfunctions below the affected spinal segment. Transplantation of bone marrow mesenchymal stem cells (BMSCs) has emerged as a potential treatment for SCI. However, the low survival as well as the differentiation rates of BMSCs within the spinal cord microenvironment significantly limit their therapeutic efficiency. Tauroursodeoxycholic acid (TUDCA), an active ingredient found in bear bile, has demonstrated its neuroprotective, antioxidant, and antiapoptotic effects on SCI. Thus, the present study was aimed to study the possible benefits of combining TUDCA with BMSC transplantation using an animal model of SCI. The results showed that TUDCA significantly enhanced BMSC viability and reduced apoptosis (assessed by Annexin V-FITC, TUNEL, Bax, Bcl-2, and Caspase-3) as well as oxidative stress (assessed by ROS, GSH, SOD, and MDA) both in vitro and in vivo. Additionally, TUDCA accelerated tissue regeneration (assessed by HE, Nissl, MAP2, MBP, TUJ1, and GFAP) and improved functional recovery (assessed by BBB score) following BMSC transplantation in SCI. These effects were mediated via the Nrf-2 signaling pathway, as evidenced by the upregulation of Nrf-2, NQO-1, and HO-1 expression levels. Overall, these results indicate that TUDCA could serve as a valuable adjunct to BMSC transplantation therapy for SCI, potentially enhancing its therapeutic efficacy. [ABSTRACT FROM AUTHOR]

Cyclocarya paliurus (CP) contains triterpene acids that can improve glucose and lipid metabolism disorders. However, controlling the composition and content of these active ingredients in CP extracts is challenging. The main active components in CP triterpene acids, including ursolic acid (UA), oleanolic acid (OA), and betulinic acid (BA), exhibit antihyperglycemic and antihypertensive effects. The response surface methodology was utilized to design and optimize the ratio of UA, OA, and BA based on the inhibition rate of pancrelipase and α-amylase. The proportional mixture of UA, OA, and BA resulted in the formation of a complex known as Cyclocarya paliurus triterpenoid acid (TAC). Se-methylselenocysteine (MSC), a compound with various physiological functions such as antioxidant properties and tumor inhibition, has been used in combination with TAC to form the TAC/MSC complex. Our data demonstrate that TAC/MSC improved palmitic acid (PA)-induced insulin resistance in HepG2 cells through activating the phosphoinositide 3-kinase (PI3K) /protein kinase B (AKT)/glycogen synthase kinase 3 beta (GSK3β) pathway. Moreover, TAC/MSC effectively improved hyperglycemia, glucose intolerance, insulin resistance, and lipid metabolism disorder in mice with type 2 diabetes mellitus (T2DM), attenuated hepatic steatosis, and reduced oxidative stress to alleviate T2DM characteristics. [ABSTRACT FROM AUTHOR]

Abstract Acetaminophen (APAP) overdose-induced hepatotoxicity is tightly associated with oxidative stress. Tetrahydrocurcumin (THC) and octahydrocurcumin (OHC), the primary and final hydrogenated metabolites of curcumin (CUR), possess stronger antioxidant activity in vitro. The present study was performed to investigate the potential and mechanism of OHC and THC against APAP-induced hepatotoxicity in parallel to CUR. Our results showed that OHC and THC dose-dependently enhanced liver function (ALT and AST levels) and alleviated histopathological deterioration. Besides, OHC and THC significantly restored the hepatic antioxidant status by miring level of MDA and ROS, and elevated levels of GSH, SOD, CAT and T-AOC. In addition, OHC and THC markedly suppressed the activity and expressions of CYP2E1, and bound to the active sites of CYP2E1. Moreover, OHC and THC activated the Keap1-Nrf2 pathway and enormously enhanced the translational activation of Nrf2-targeted gene (GCLC, GCLM, NQO1 and HO-1) against oxidative stress, via inhibiting the expression of Keap1 and blocking the interaction between Keap1 and Nrf2. Particularly, OHC and THC exerted superior hepato-protective and antioxidant activities to CUR. In conclusion, OHC and THC possess favorable hepato-protective effect through restoring antioxidant status, inhibiting CYP2E1 and activating Keap1-Nrf2 pathway, which might represent promising antioxidants for the treatment of APAP-induced hepatotoxicity. Graphical abstract Image 1 Highlights • OHC and THC effectively attenuated hepatotoxicity induced by APAP. • OHC and THC possessed superior hepato-protective effect to CUR. • OHC and THC suppressed the CYP2E1 activity and expression, and bound to CYP2E1. • OHC and THC activated the Keap1-Nrf2 pathway and induced the Nrf2-targeted genes. • OHC and THC blocked the interaction between Keap1 and Nrf2. [ABSTRACT FROM AUTHOR]

Yak is a wild bovine species living on the Qinghai Tibet Plateau that demonstrates good adaptability to the hypoxic environment. Chicoric acid, a natural phenolic compound, is known as having anti-oxidant, antiviral, anti-inflammatory and analgesic properties. However, its effect on hypoxia adaptability of yak is still unclear. In this study 40 yaks were selected that were of similar age, parity and weight, and divided into the control group and experimental groups 1, 2, 3, randomly. Results showed that chicoric acid significantly improved RBC, HGB, and WBC. There are significantly beneficial effects to increasing total protein contents (): all treatments increased HDL-C contents, and supplementations 100mg/h significantly decreased the content of TG on the 60th day (). Contents of the serum related enzymes like ALP, GOP and GPT showed varying degrees of change, but no significant differences and the indexes of anti-oxidant capacity (T-AOC and GSH-Px) were significantly improved (), but MDA was decreased () under the action of the chicoric acid. Hypoxia-inducible factor in serum such as HIF-2, EPO, ROS, Fe and Tf are all significantly decreased (). The myocardial mitochondrial parameters mtDNA, UCP2, PGC1-, NRF1 and mitochondrial complexes were altered remarkably. Some indicators of glucose metabolism presented variation trends. Taken together, chicoric acid has shown a positive effect on the adaptive ability of yak in high altitude, hypoxic environment in plateau areas. Our findings reported a new potential means to enhance immunity and inflammatory response and improve the anti-oxidant capacity. [ABSTRACT FROM AUTHOR]

Background 5-Aminolevulinic acid photodynamic therapy (ALA-PDT) has been used for the treatment of skin photoaging. It can significantly improve the appearance of fine lines, dotted pigmentation, and roughness of photoaged skin. However, the mechanisms by which ALA-PDT yields rejuvenating effects on photoaged skin have not been well elucidated. Thus, in this study we explored the effects of ALA-PDT in photoaged fibroblasts. Methods We established a stress-induced premature senescence (SIPS) model by repeated exposures of human dermal fibroblasts (HDFs) to ultraviolet B (UVB) irradiation. Cells were irradiated by red light laser at 635 nm wavelength (50 mW/cm 2 ). Intracellular protoporphyrin IX (PpIX) was detected by confocal microscopy. Intracellular reactive oxygen species (ROS) level and mitochondrial membrane potential (MMP) change were detected by fluorescence microscopy and flow cytometry. Morphological changes were observed by optical microscopy. Proliferative activity was measured by a cell counting kit-8 (CCK-8). Cell apoptosis was detected by fluorescence microscopy using Hoechst staining and flow cytometry using annexin V/propidium Iodide double staining. Results Intracellular PpIX fluorescence in UVB-induced premature senescent HDFs (UVB-SIPS-HDFs) reached the highest intensity after incubation with 1.00 mmol/L ALA for 6 h ( P < 0.05). Compared with control group, intracellular ROS level, MMP, and apoptotic rate were increased ( P < 0.05) and proliferative activity was decreased ( P < 0.05) in UVB-SIPS-HDFs treated with ALA-PDT, which were positively correlated to ALA incubation time and red light laser dose. Conclusion Our study demonstrated that ALA-PDT elicits oxidative damage and apoptosis in photoaged fibroblasts in vitro , which may be the basis for the rejuvenating effects on photoaged skin. [ABSTRACT FROM AUTHOR]

Abstract: Exposure of skin to solar ultraviolet (UV) radiation induces photo-damage. Ultraviolet B (UVB) is the major component of UV radiation which induces the production of reactive oxygen species (ROS) and plays an important role in photo-damage. Hydrogen gas reduces ROS and alleviates inflammation. In this study, we sought to demonstrate that hydrogen-rich saline has the effect on skin injuries caused by UVB radiation. UVB radiation was irradiated on female C57BL/6 rats to induce skin injury. Hydrogen-rich saline and nitrogen-rich saline were administered to rats by intraperitoneal injection. Skin damage was detected by microscope after injury. UVB radiation had a significant affection in tumor necrosis factor alpha, interleukin (IL)-1β and IL-6 levels, tissue superox-ide dismutase, malondialdehyde and nitric oxide activity. Hydrogen-rich saline had a protective effect by altering the levels of these markers and relieved morphological skin injury. Hydrogen-rich saline protected against UVB radiation injury, possibly by reducing inflammation and oxidative stress. [Copyright &y& Elsevier]

Recent studies have demonstrated that selenium (Se) reduces the accumulation of heavy metals in rice tissues. However, the interaction between Se and mercury (Hg) in rice genotypes with high Se content remains to be further investigated. In this study, we used high Se genotypes Z2057B and Z5097B and low Se genotype Yuenong to explore the dynamics of Se and Hg in various tissues. The results showed that high Se genotypes, coupled with low concentrations of exogenously applied Se, significantly reduced the uptake of Hg in rice plants. The findings indicated the following order of Hg accumulation: Roots> third leaf > second leaf > first leaf > stem > grains. Observations revealed that both high Se genotypes and Se supplementation significantly restricted the majority of Hg concentration in roots and minimized its translocation to the aerial parts of the rice plant. In high Se genotypes subjected to mercury stress, MDA accumulation was significantly reduced, and SOD antioxidant activity was enhanced in stem and leaves at jointing, booting, heading, and maturity stages as compared to low Se genotypes. The application of 1.0 mg of Se per kg soil significantly improved the agronomic and physiological characteristics, reduced the Hg contents in aerial parts, and increased the Se contents in polished rice grains. Hence, the results lead to the conclusion that (i) cultivating high Se rice genotypes is a viable approach to decrease the Hg accumulation in rice grains and serves as a crucial strategy to fulfill daily Se requirements, particularly for populations suffering from Se deficiency (ii) supplementing ordinary rice with 1–3 mg kg−1 of Se can effectively reduce Hg accumulation and improve the quality of the grains. • High Se rice genotypes reduced the translocation and bioaccumulation of Hg from roots to the polished grains of rice. • Application of a low dose (1–3 mg kg−1) of exogenously Se reduced the oxidative stress that was caused by the Hg pollution. • Cultivation of high Se genotypes can meet the daily Se requirement of the people in rice consumption areas. [ABSTRACT FROM AUTHOR]

Abstract: Mounting evidence indicates that signaling via VEGF receptors (VEGFRs) extends beyond blood vessel formation. Recently, VEGFRs are also found to be constitutively expressed in keratinocytes and epidermal appendages. Here, we show that the expression of VEGFRs (including VEGFR-1, VEGFR-2, and NRP-1) was significantly enhanced by moderate dose of ultraviolet B (UVB) in normal human keratinocytes and epidermis. The elevated expression of VEGFRs by UVB was independent of autocrine stimulation by their natural ligand, VEGF, but mainly mediated through hypoxia and oxidative stress. Moderate dose UVB also promoted tyrosine phosphorylation of VEGFR-1 and VEGFR-2, this effect was again VEGF independent. Both α and δ isoforms of protein kinase C (PKC) were required for UVB-induced phosphorylation of VEGFR-1, but only the δ isoform was required for VEGFR-2 phosphorylation. The phosphorylation of VEGFRs or isoforms of PKC was completely inhibited by PP2, a specific inhibitor for Src family kinases (SFKs), indicating that SFKs are upstream of PKC and VEGFRs. Moderate dose UVB-induced VEGF exerted an anti-apoptotic effect for keratinocytes, whereas high dose UVB-induced VEGF played as an inflammatory factor. Of note, neutralization of VEGFR-2 but not VEGFR-1 exacerbated UVB-induced cell death and reduced survival of keratinocytes. Furthermore, VEGFR-2 neutralization inhibited the activation of ERK1/2 and Akt by UVB, suggesting that VEGFR-2 signaling was involved in the pro-survival mechanism via ERK1/2 and PI3-K/Akt pathway. Taken together, we demonstrate for the first time that VEGFR-2 signaling is activated and promotes survival of keratinocytes under moderate dose of UVB irradiation. [Copyright &y& Elsevier]

Chronic hyperglycemia, proinflammatory state, and oxidative stress are implicated in the etiology of mild cognitive impairment (MCI) in type 2 diabetes mellitus (T2DM) patients. However, roles and mechanisms of the diabetes-related dys-regulation of serum d -ribose in the pathogenesis remain unclear. This study was to assess: 1) changes of serum d -ribose in T2DM patients with or without MCI compared with healthy controls; and 2) associations of serum d -ribose with key biomarkers of ribosylation [advanced glycation end products (AGEs) and receptor for advanced glycation end products (RAGE)], inflammation (IL-6 and NF-κB) and oxidative stress [oxidized low density lipoproteins (ox-LDL), advanced oxidation protein products (AOPP), total thiol, and non-protein thiol)]. A cross-sectional study was conducted with 1564 initial participants including 362 T2DM patients. Based on their fasting blood glucose concentrations and Montreal cognitive assessment (MoCA) scores, we selected 89 participants and divided them into three groups: 27 healthy controls, 26 T2DM patients with normal cognition, 36 T2DM patients with MCI. All participants were gone through standard anthropometric tests and biochemical examinations of serum clinical profiles and concentrations of d -ribose, AGE, RAGE, IL-6, NF-κB, ox-LDL, AOPP, total thiol, and non-protein thiol. Serum concentrations of d -ribose, ox-LDL, and AOPP were greater (P < 0.05) in the T2DM-MCI patients than that in the T2DM or controls. Serum d -ribose exhibited a positive correlation (P < 0.05) with serum AGEs, RAGE, ox-LDL, and fasting blood glucose, but a negative correlation (P < 0.05) with MoCA score. This negative relationship remained (P < 0.05) after adjusting various covariates, and was found to be mediated (P < 0.05) by serum ox-LDL. In conclusion, our results reveal serum ox-LDL as a potential mediator for the inverse relationship between the elevation of serum d -ribose concentration and the decline of cognitive performance in the T2DM-MCI patients. [Display omitted] • Serum d -ribose and ox-LDL concentrations were elevated in T2DM-MCI patients. • Serum d -ribose and ox-LDL were positively correlated in T2DM-MCI patients. • Serum d -ribose and ox-LDL were negatively correlated with cognitive function. • Serum Ox-LDL mediated the relationship between serum d -ribose and cognition. [ABSTRACT FROM AUTHOR]

Perfluorooctanoic acid (PFOA) is a synthetic perfluorinated compound, which has been reported to exert adverse effect on the pregnancy. However, whether it is associated with alteration of luteal function remains unknown. Mice were administered PFOA by gavage from gestational days (GD) 1–7 or 13. PFOA treatment did not significantly affect numbers of embryo implantation. Nevertheless, on GD 13, 10 mg/kg PFOA treatment significantly increased numbers of resorbed embryo. Furthermore, PFOA exposure markedly reduced serum progesterone levels but did not affect estradiol levels. Treatment also showed concomitant decreases in transcript levels for key steroidogenic enzymes, and reduced numbers and sizes of corpora lutea. In addition, PFOA administration inhibited activities of superoxide dismutase and catalase, and increased generation of hydrogen peroxide and malondialdehyde, and down-regulated level of Bcl-2 and up-regulated p53 and BAX proteins. In conclusion, PFOA exposure significantly inhibits luteal function via oxidative stress and apoptosis in pregnant mice. [ABSTRACT FROM AUTHOR]