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Stroke is an acute cerebrovascular disease with high morbidity, mortality, and disability, making it the second leading cause of death worldwide. Ischemic stroke (IS) accounts for the majority of strokes, and its pathogenesis is complex, often involving complications and sequelae. Currently, conventional clinical approaches are ineffective, with few drugs available for intravenous thrombolysis and mechanical thrombolysis limited by a short time window. With the poor efficacy of monotherapy, the search for new complementary or alternative therapies has become the focus of researchers. In traditional medicine, Chinese aromatherapy has a long history of using aromatic medicines to treat IS. Natural essential oils (EOs), as the main pharmacological substances in aromatic drugs, are composed of different ratios of active metabolites with multi-targets and multi-components, which makes EOs have a wide range of pharmacological effects. Modern studies have also shown that EOs extracts and isolated monomers are beneficial for pathologically complex CIS. Therefore, this paper summarizes the EOs and monomers obtained from EOs that can prevent and treat IS in the last 20 years, and finds that EOs exert their anti-CIS effects mainly through anti-oxidative stress, anti-inflammation, anti-apoptosis, and inhibition of excitotoxicity. The amelioration of IS complications by natural EOs and their active monomer components for the treatment of IS are further discussed.

Plasmalogens (PLs) are critical to human health. Studies have reported a link between the downregulation of PLs levels and cognitive impairments in patients with Alzheimer's disease (AD). However, the underlying mechanisms remain to be clarified. In the present study, an AlCl 3 -induced AD zebrafish model was established, and the model was used to elucidate the neuroprotective effects of PLs on AD by analysing the transcriptional profiles of zebrafish in the control, AD model, AD_PL, and PL groups. Chronic AlCl 3 exposure caused swimming performance impairments in the zebrafish, yet PLs supplementation could improve the dyskinesia recovery rate in the AD zebrafish model. Through transcriptional profiling, a total of 5413 statistically significant differentially expressed genes (DEGs) were identified among the groups. In addition to the DEGs involved in amino acid metabolism, we found that the genes related to iron homeostasis, lipid peroxidation, and oxidative stress, all of which contribute to ferroptosis, were dramatically altered among different groups. These results suggest that seafood-derived PLs, in addition to their role in eliminating oxidative stress, can improve the swimming performance in AlCl 3 -exposed zebrafish partly by suppressing neuronal ferroptosis and accelerating synaptic transmission at the transcriptional level. This study provides evidence for PLs to be developed as a functional food supplement to relieve AD symptoms.

Triptolide is a natural, biologically active compound extracted from the Chinese herb Tripterygium Wilfordii hook, that possesses potent immunosuppressive properties. In the course of our study, we examined the effects of triptolide on stimulated murine macrophages and demonstrated that triptolide inhibited superoxide anion production, NO production, and the expression of iNOS mRNA and the mRNA of some key inflammation-related cytokines, namely TNF-alpha, IL-1beta, IL-6 and IFN-gamma. This inhibition was accompanied by the inhibition of nuclear transcription factor NF-kappaB activation. We further developed a mathematical model to simulate interplay between triptolide, ROS, NF-kappaB, iNOS and related cytokines. Our results suggest that triptolide acts to regulate inflammation through NF-kappaB-mediated inhibition of inflammation-related cytokines and the production of superoxide anion and NO.

Aims: We investigated whether human umbilical cord mesenchymal stem cell (hUC‐MSC)‐derived exosomes bear therapeutic potential against lipopolysaccharide (LPS)‐induced neuroinflammation. Methods: Exosomes were isolated from hUC‐MSC supernatant by ultra‐high‐speed centrifugation and characterized by transmission electron microscopy and western blotting. Inflammatory responses were induced by LPS in BV‐2 cells, primary microglial cultures, and C57BL/6J mice. H2O2 was also used to induce inflammation and oxidative stress in BV‐2 cells. The effects of hUC‐MSC‐derived exosomes on inflammatory cytokine expression, oxidative stress, and microglia polarization were studied by immunofluorescence and western blotting. Results: Treatment with hUC‐MSC‐derived exosomes significantly decreased the LPS‐ or H2O2‐induced oxidative stress and expression of pro‐inflammatory cytokines (IL‐6 and TNF‐α) in vitro, while promoting an anti‐inflammatory (classical M2) phenotype in an LPS‐treated mouse model. Mechanistically, the exosomes increased the NRF2 levels and inhibited the LPS‐induced NF‐κB p65 phosphorylation and NLRP3 inflammasome activation. In contrast, the reactive oxygen species scavenger NAC and NF‐κB inhibitor BAY 11–7082 also inhibited the LPS‐induced NLRP3 inflammasome activation and switched to the classical M2 phenotype. Treatment with the NRF2 inhibitor ML385 abolished the anti‐inflammatory and anti‐oxidative effects of the exosomes. Conclusion: hUC‐MSC‐derived exosomes ameliorated LPS/H2O2‐induced neuroinflammation and oxidative stress by inhibiting the microglial NRF2/NF‐κB/NLRP3 signaling pathway. [ABSTRACT FROM AUTHOR]

Chronic respiratory diseases are long-term conditions affecting the airways and other lung components that are characterized by a high prevalence, disability rate, and mortality rate. Further optimization of their treatment is required. Natural products, primarily extracted from organisms, possess specific molecular and structural formulas as well as distinct chemical and physical properties. These characteristics grant them the advantages of safety, gentleness, accessibility, and minimal side effects. The numerous advances in the use of natural products for treating chronic respiratory diseases have provided a steady source of motivation for new drug research and development. In this paper, we introduced the pathogenesis of chronic respiratory diseases and natural products. Furthermore, we classified natural products according to their mechanism for treating chronic respiratory diseases and describe the ways in which these products can alleviate the pathological symptoms. Simultaneously, we elaborate on the signal transduction pathways and biological impacts of natural products' targeting. Additionally, we present future prospects for natural products, considering their combination treatment approaches and administration methods. The significance of this review extends to both the research on preventing and treating chronic respiratory diseases, as well as the advancement of novel drug development in this field. [ABSTRACT FROM AUTHOR]

Cardiovascular disease is a high incidence and mortality rate disease worldwide. Exercise training has become an established evidence-based treatment strategy that is beneficial for many cardiovascular diseases. This study aimed to investigate the effects of exercise on hyperlipidemia-induced cardiac damage in apolipoprotein E-deficient (ApoE−/−) mice. Male ApoE−/− mice were randomly divided into the following four groups: normal diet (ND), normal diet + exercise training (ND + E), high-fat diet (HFD), and high-fat diet + exercise training (HFD + E). Exercise training consisted of swimming for 40 min, 5 days/week for 12 weeks. After 12 weeks, histopathological alterations in cardiac tissue and the serum were measured. Furthermore, the NOX4, NRF2, SIRT1, TGF-β, HO-1, collagen III, Smad3, Bax, Bak, Bcl-2, Bcl-xl, IL-1β, IL-6, and IL-18 expression levels were evaluated using immunohistochemistry and western blotting; Results: the serum levels of SIRT1, GSH-Px, and SOD were lower in ApoE−/− HFD mice compared with those in ApoE−/− HFD + E mice. Significant pathological changes were observed in the ApoE−/− HFD + E group compared with those in the ApoE−/− HFD group. Increased levels of oxidative stress, fibrosis, and apoptosis, and decreased antioxidant expression in the ApoE−/− HFD group compared with those in ApoE−/− HFD + E mice. Exercise exerts protective effects against cardiac damage caused by hyperlipidemia. [ABSTRACT FROM AUTHOR]

This project aimed to investigate the protective mechanism of sufentanil pretreatment on myocardial ischemia-reperfusion injury (IRI). An in vivo rat model of myocardial IRI and an in vitro cultured cardiomyocyte model of hypoxia-reoxygenation (H/R) were used to confirm the anti-oxidation and anti-autophagy effects of sufentanil. The interaction between miR-125a and damage-regulated autophagy regulator 2 (DRAM2) was verified by luciferase reporter assay. We showed that pretreatment with sufentanil suppressed myocardial damage caused by IRI in rats by inhibiting oxidative stress and mitochondrial autophagy. Furthermore, the cardioprotective mechanism of sufentanil was mediated by miR-125a. MiR-125a targeted DRAM2 to ameliorate cardiomyocyte autophagy and oxidative injury following H/R treatment. In conclusion, our results demonstrated that sufentanil pretreatment produced a protective effect against myocardial IRI via regulating miR-125a/DRAM2 signaling axis. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) is a frequent complication of sepsis with hallmarks including inflammation and oxidative stress. A large amount of oleanolic acid derivatives (TO) have been isolated from Gardenia jasminoides var. radicans, a traditional Chinese medicine with anti-inflammatory efficacy; thus, the aim of the present study was to evaluate the protective effects of TO on injury in a murine model of endotoxemic AKI. Kidney function, inflammation, oxidative stress, apoptosis, white blood cell count, TLR4/NF-κB/NLRP3 pathway involvement and metabolic profiling of the serum were evaluated. The results show that TO significantly ameliorated renal function in mice with LPS-induced AKI; 2-deoxy- D -glucose (2-DG) optical probe imaging indicated that TO markedly reduced the levels of inflammation; flow cytometry demonstrated that TO had an excellent antioxidant effect, regulating immune cells; Western blotting indicated that TO inhibited the TLR4/NF-κB/NLRP3 signaling pathway; and metabolic profiling of the serum also demonstrated the protective effects of TO on injury in a murine model of endotoxemic AKI. In summary, TO renoprotection involves the attenuation of LPS-induced renal inflammation and oxidative stress, which may be mediated via inhibition of the TLR4/NF-κB/NLRP3 signaling pathway. [ABSTRACT FROM AUTHOR]

Preeclampsia (PE) remains the leading cause of maternal and fetal morbidity and mortality. Excessive apoptosis of the placenta and poor remodeling of spiral arteries caused by insufficient invasion of trophoblast cells into uterus have been implicated in the pathogenesis of PE. Accumulating evidence showed that heat shock protein 20 (HSP20) is closely associated with the proliferation, apoptosis, and metastasis of tumor cells. However, little is known about whether HSP20 plays a role in the development of PE. In this study, we detected the apoptosis index and the expressions of HSP20 and apoptosis-associated proteins in the placentas from PE and normal pregnancies. We found that HSP20 was reversely related to the apoptosis rate and the levels of proapoptotic proteins. Moreover, we identified that HSP20 could suppress the proliferation and apoptosis of trophoblast cells, turning them into a more invasive phenotype. Additionally, H2O2-induced oxidative stress was significantly alleviated, and several key proteins on the Akt signaling pathway were upregulated in HSP20-overexpressing trophoblast cells. These findings strongly suggested that HSP20 might play a role in the remodeling of spiral arteries through affecting the invasiveness of extravillous trophoblast cells via Akt signaling pathway, and the dysregulation of it might contribute to the pathophysiology of PE. [ABSTRACT FROM AUTHOR]

Background: Rehmannia Glutinosa Libosch. is applied for the treatment of renal and inflammatory-related diseases, and oleic acid (OA) is a compound isolated from Rehmannia Glutinosa Libosch.. Unfortunately, the pharmacological activity of OA on LPS treated acute kidney injury (AKI) has not been investigated.Aims: The research is aiming to probe the activities of OA on LPS-induced AKI.Methods: Information of OA effect on AKI were from network pharmacology. H&E staining, creatinine (CRE) and urea nitrogen (UN) were performed to evaluate the activities of OA on kidney function. Inflammatory factors in serum were measured by cytometric bead array. Increased ratio of reactive oxygen species (ROS) in kidney and immune cells in the peripheral blood were determined by flow cytometry (FCM). PPAR-γ, MAPK and apoptotic signaling pathways were measured by Western blot. Then, a metabolomics approach was utilized to investigate OA's response to AKI. The role of salirasib (FTS, Ras inhibitor) in OA acted on ROS, Ca2+, MMP and Ras signaling pathway in LPS treated NRK-52e cells were investigated by FCM and In-cell western.Results: It is proved that OA effetively ameliorated renal function, alleviated inflammatory response and oxidative stress, and transformed apoptotic, MAPK and PPAR-γ signaling pathways in mice with AKI, regulated phenylalanine metabolism, purine metabolism, sphingolipid metabolism, taurine and hypotaurine metabolism, moreover, the role of OA in injury of NRK-52e was blocked by FTS.Conclusion: In a word, OA could alleviate AKI by restraining inflammation and oxidative stress via regulating the Ras/MAPKs/PPAR-γ signaling pathway, phenylalanine metabolism, purine metabolism, sphingolipid metabolism and taurine and hypotaurine metabolism, which might be a useful strategy for treating AKI. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a common neurodegenerative disease; tea components have important neuroprotective effects. This article explores the effects and mechanisms of Qingxiang Tiguanyin (Tgy-Q), Nongxiang Tieguanyin (Tgy-N), and Chenxiang Tieguanyin (Tgy-C) extracts on APP/PS1 AD model mice. Morris water maze and new object recognition experiments show that Tieguanyin extracts can effectively enhance the cognitive ability of APP/PS1 mice. H&E staining, Nissl staining, and immunohistochemical staining show that Tieguanyin extracts make nerve cell boundaries and nucleoli become clearer, relieve nucleus pyknosis, and effectively reduce Aβ1-40 and Aβ1-42 in the hippocampus and cortex. They also restore the morphology of microglia and astrocytes. In addition, Tieguanyin extracts can balance the oxidative stress level in the brain of APP/PS1 mice by improving the antioxidant capacity. Western blot results show that Tieguanyin extracts can reduce the expression of NF-κB p65, TNF-α, IL-1β, IL-6, COX-2, and iNOS in mouse brain, which demonstrates that Tieguanyin extracts improves cognitive ability by alleviating inflammation. This article demonstrates for the first time that Tieguanyin extracts can inhibit the excessive activation of the NF-κB p65 signaling pathway and improve the antioxidant capacity in the cerebral cortex and hippocampus, to improve the cognitive ability of APP/PS1 mice. Our results shed light into the beneficial of Tieguanyin tea extracts on preventing and alleviating AD diseases. [ABSTRACT FROM AUTHOR]

The functional analysis of dr1127, a novel gene in Deinococcus radiodurans was performed in this paper. The dr1127 gene was found occasionally in our microarray and 2-DE gel experiments. Mutation of the dr1127 gene decreased the γ-radiation and H2O2 resistance of D. radiodurans, and weakened the scavenging abilities of cell extracts for free radicals (superoxide anion, hydrogen peroxide, and hydroxyl radical). Further oxidative damage assays demonstrated that the purified DR1127 protein of D. radiodurans could bind to double stranded DNA in vitro and protect DNA from oxidative damage in this way. These results suggest that the dr1127 gene is an important gene that can maintain γ-radiation and oxidative resistance in D. radiodurans and may take part in the oxidative stress process. [ABSTRACT FROM AUTHOR]

Objective: Oxidative stress may be associated with polycystic ovary syndrome (PCOS) and poor outcomes after assisted reproduction treatment. It is unclear if systematic oxidative stress is correlated with live birth rate in patients with PCOS after controlled ovarian stimulation. This study aimed to investigate the serum oxidative stress markers on the day of trigger hCG and its relationship with live birth rate in young non-obese women with or without PCOS undergoing in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment.Study Design: In this prospective cohort study, 50 patients with PCOS and 50 patients without PCOS aged less than 35 years and undergoing IVF/ICSI between February 2017 and January 2018 were studied. The body mass index (BMI) of all participants was less than 28 kg/m2. Serum malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GPx) levels on the day of hCG were measured. Demographic and cycle characteristics, embryo laboratory data and pregnancy outcomes after fresh embryo transfer were analyzed. Univariate analysis and logistic regression analysis were used to analyze independent variables predicting the live birth rate.Results: After conventional ovarian stimulation, the patients with PCOS had higher serum MDA and GPx concentrations (P < 0.03) and lower serum SOD levels (P < 0.03) on the hCG trigger day than the controls. Further, the serum MDA and GPx levels on the trigger day were also positively correlated with the number of good quality embryos (R = 0.26, P = 0.01; R = 0.21, P = 0.04; respectively). However, cycle characteristics, IVF/ICSI outcomes and pregnancy outcomes were comparable between the two groups. Multivariate logistic regression analysis showed that the rate of good quality embryos (OR 1.04, 95 %CI 1.01-1.06, P = 0.005) and the duration of infertility (OR 0.74, 95 %CI 0.56-0.98, P = 0.04) were predictive factors of live birth rate. The ROC curve analysis showed the AUC for the model was 0.76 (95 %CI: 0.67-0.86, P < 0.001).Conclusion: The data suggest that moderate systemic oxidative stress on the hCG trigger day had no detrimental effects on live birth rate in young and non-obese patients with PCOS after IVF/ICSI treatment. [ABSTRACT FROM AUTHOR]

Background Selenium (Se) is an essential micronutrient required by avian species. Dietary Se/vitamin E deficiency induces three classical diseases in chicks: exudative diathesis, nutritional pancreatic atrophy, and nutritional muscular dystrophy. Scope of review This review is to summarize and analyze the evolution, regulation, and function of avian selenogenome and selenoproteome and their relationship with the three classical Se/vitamin E deficiency diseases. Major conclusions There are 24 selenoproteins confirmed in chicks, with two avian-specific members (SELENOU and SELENOP2) and two missing mammalian members (GPX6 and SELENOV). There are two forms of SELENOP containing 1 or 13 selenocysteine residues. In addition, a Gallus gallus gene was conjectured to be the counterpart of the human SEPHS2. Expression of selenoprotein genes in the liver, pancreas, and muscle of chicks seemed to be highly responsive to dietary Se changes. Pathogeneses of the Se/vitamin E deficient diseases in the chicks were likely produced by missing functions of selected selenoproteins in regulating cellular and tissue redox balance and inhibiting oxidative/reductive stress-induced cell death. General significance Gene knockout models, similar to those of rodents, will help characterize the precise functions of avian selenoproteins and their comparisons with those of mammalian species. [ABSTRACT FROM AUTHOR]

• 5-O-methyldihydroquercetin (GS1) and cilicicone B (GS2) were isolated from Spina Gleditsiae. • GS1 and GS2 have reno-protective effects via TLR4 signaling pathway. • GS1 and GS2 might be potential clinical drugs for AKI. Inflammation and oxidative stress are the major mechanisms implicated in lipopolysaccharide (LPS)-induced AKI. Spina Gleditsiae is a traditional Chinese anti-inflammatory medicine, from which a large number of flavonoids, such as 5-O-methyldihydroquercetin (GS1) and cilicicone B (GS2), were isolated in the present study. Here, we examined the reno-protective effects and potential underlying mechanisms of GS1 and GS2 in mice with LPS-induced AKI. We analyzed renal function; the serum metabolic profile, inflammatory cytokine levels, peripheral white blood cell count, renal cell apoptosis, renal oxidant and antioxidant levels, and renal expression levels of toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), TIR-domain-containing adapter-inducing interferon-β (TRIF), nuclear factor-ĸB (NF-ĸB), interferon regulatory factor 3 (IRF3), NOD-, LRR- and pyrin domain-containing 3 (NLRP3, inflammasome), cleaved caspase-1, and interleukin 1 receptor type I (IL-1R1) in mice with LPS-induced AKI. GS1 and GS2 improved renal function and significantly reduced the levels of inflammatory cytokines and oxidative stress markers. In addition, PCA score scatter plots suggest that the GS1 and GS2 groups were clustered with the control group, indicating that these compounds contributed to the recovery of mice with AKI toward the normal condition. Moreover, GS1 and GS2 inhibited the expression of TLR4, MyD88, TRIF, p-NF-ĸB, p-IRF3, NLRP3, cleaved caspase-1, and IL-1R1. The reno-protective effects of GS1 and GS2 are mediated via the MyD88/TRIF and NLRP3 pathways to reduce inflammation and oxidative stress through TLR4 signaling. [ABSTRACT FROM AUTHOR]