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• Fluoxeine-induced hepatotoxicity dependented ferroptosis occurrence. • Fluoxetine can directly bind to ATF3 and FSP1 targets. • Rehmannia glutinosa can alleviate fluoxetine-induced liver injury. • Co-catalpol can protect against fluoxetine-induced liver injury. • Catalpol reduced fluoxetine's hepatotoxicity by ferroptosis inhibited by ATF3/FSP1. Fluoxetine is often used as a well-known first-line antidepressant. However, it is accompanied with hepatogenic injury as its main organ toxicity, thereby limiting its application despite its superior efficacy. Fluoxetine is commonly traditionally used combined with some Chinese antidepressant prescriptions containing Rehmannia glutinosa (Dihuang) for depression therapy and hepatoprotection. Our previous experiments showed that co-Dihuang can alleviate fluoxetine-induced liver injury while efficiencies, and catalpol may be the key ingredient to characterize the toxicity-reducing and synergistic effects. However, whether co-catalpol can alleviate fluoxetine-induced liver injury and its toxicity-reducing mechanism remain unclear. On the basis of the first recognition of the dose and duration at which pre-fluoxetine caused hepatic injury, co-catalpol's alleviation of fluoxetine-induced hepatic injury and its pathway was comprehensively elucidated. The hepatoprotection of co-catalpol was evaluated by serum biochemical indexes sensitive to hepatic injury and multiple staining techniques for hepatic pathologic analysis. Subsequently, the pathway by which catalpol alleviated fluoxetine-induced hepatic injury was predicted by network pharmacology to be predominantly the inhibition of ferroptosis. These were validated and confirmed in subsequent experiments with key technologies and diagnostic reagents related to ferroptosis. Further molecular docking showed that activating transcription factor 3 (ATF3) and ferroptosis suppressor protein 1 (FSP1) were the the most prospective molecules for catalpol and fluoxetine among many ferroptosis-related molecules. The critical role of ATF3/FSP1 signaling was further observed by surface plasmon resonance, diagnostic reagents, transmission electron microscopy, Western blot, real-time PCR, immunofluorescence, and immunohistochemistry. Results showed that fluoxetine directly bound to ATF3 and FSP1; agonisting ATF3 or blocking FSP1 abolished the alleviation of catalpol on fluoxetine-induced liver injury, and both exacerbated ferroptosis. Moreover, co-catalpol significantly enhanced the antidepressant efficacy of fluoxetine against depressive behaviours in mice. The hepatic impairment properties of fluoxetine were largely dependent on ATF3/FSP1 target-mediated ferroptosis. Co-catalpol alleviated fluoxetine-induced hepatic injury while enhancing its antidepressant efficacy, and that ATF3/FSP1 signaling-mediated inhibition of ferroptosis was involved in its co-administration detoxification mechanism. This study was the first to reveal the hepatotoxicity characteristics, targets, and mechanisms of fluoxetine; provide a detoxification and efficiency regimen by co-catalpol; and elucidate the detoxification mechanism. [Display omitted] [ABSTRACT FROM AUTHOR]

• AESAA significantly reduces cognitive impairment in d -gal-induced aging mice. • AESAA alleviates oxidative damage in d -gal-induced aging mice. • AESAA suppresses d -gal-induced neuroinflammation by decreasing pro-inflammatory cytokines. • AESAA takes effects may through inhibiting RAGE/MAPK/NF-KB signaling pathway. Aging is a natural process that accompanied with progressive cognitive deficits and functional decline in organisms. Selenium (Se), an essential trace element, exhibits antioxidative and anti-inflammatory abilities. Here, our study aimed to investigate the protective effects of aqueous extracts of Se-enriched Auricularia auricular (AESAA) on aging mice induced by d -galactose (D -gal) and explore its potential mechanism. d -gal was administered (100 mg/kg) subcutaneously for 12 weeks to establish an aging mouse model. Morris water maze (MWM) test was conducted to assess the cognitive deficits of mice. Superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT) activities and malondialdehyde (MDA) level in hippocampus were measured to evaluate oxidative stress. The contents of pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β) and interleukin-6 (IL-6) in hippocampus were determined by ELISA method. Further, hippocampal levels of RAGE, p-Erk, p-JNK, p-P38 and p-NF-κB were detected by western blot and the RAGE expression was confirmed by immunohistochemistry. We found that AESAA supplementation significantly decreased d -gal-induced cognitive deficits, as evidenced by better performance in the MWM test. Furthermore, AESAA treatment attenuated oxidative stress and decreased the contents of pro-inflammatory cytokines in hippocampus. Importantly, AESAA inhibited the up-regulation of RAGE, p-Erk, p-JNK, p-P38 in the hippocampus of d -gal treated mice. Moreover, the results also indicated that AESAA inhibited p-NF-κB and p-IκBα expression. In conclusion, our findings suggest that AESAA effectively decreases cognitive impairment, alleviates oxidative damage and neuroinflammation in mice through s RAGE/MAPK/NF-κB signaling pathway, which provides a potential therapy for delaying the aging process. [ABSTRACT FROM AUTHOR]

The protective effects of L. plantarum C88 against chronic alcohol-induced liver injury in mice were investigated. The pretreatment with L. plantarum C88 significantly decreased the levels of alanine transaminase and aspartate aminotransferase in chronic alcohol-challenged mice. L. plantarum C88 was also found to suppress the content of malondialdehyde (MDA) and enhance the activity of superoxide dismutase (SOD) in the liver, which are well-correlated with the downregulation of hepatic cytochrome P450 2E1 and upregulation of nuclear factor erythroid 2-related factor 2 (Nrf2). Moreover, L. plantarum C88 significantly abrogated the increased serum levels of TNF-α, IL-6, and IFN-γ induced by ethanol. L. plantarum C88 ameliorated gut leakiness by upregulating the expressions of tight junction proteins and suppressed the endotoxin-mediated inflammation by decreasing P38 phosphorylation and down-regulating NF-κB. These results demonstrate that L. plantarum C88 efficiently protects against alcoholic chronic liver injury. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Zuojin Pill (ZJP), a traditional Chinese medicinal decoction, contains two herbal drugs: Coptis chinensis Franch. and Tetradium ruticarpum (A. Juss.) Hartley in the ratio of 6:1 (w/w). In this study, ZJP was evaluated for its gastroprotective potential against mucosal lesions induced by ethanol in mice. Materials and methods 50 mice were assigned to 5 groups: groups 1 and 2 were given distilled water orally. Group 3 was administered omeprazole 20 mg/kg, groups 4 and 5 were given ZJP (1 g/kg, 2 g/kg, respectively). After an additional hour, the mice in groups 2–5 received ethanol (0.2 ml/kg) orally while group 1 received distilled water instead. Mice were killed after 4 h and their serum and stomachs subjected to further studies. The superoxidase dismutase (SOD) activities and malondialdehyde (MDA) level in serum were assayed by SOD and MDA kits, respectively. The myeloperoxidase (MPO) activities in stomachs were assayed by MPO kit. The levels of inflammatory mediators including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) in serum were assayed by enzyme-linked immunosorbent assay method (ELISA). Pathological changes were observed by hematoxylin-eosin (HE) staining. The levels of nuclear factor-кBp65 (NF-кBp65), P-NF-кBp65, P-IкBα, IкBα, P-IKKα, IKKα, P-IKKβ, IKKβ in stomachs were assayed by western blot. Results The data showed that treatment with the ZJP markedly attenuated MPO, MDA, TNF-α, IL-6, IL-1βand increased SOD; and ZJP also decreased protein levels of P-NF-кBp65, P-IкBα, P-IKKαand P-IKKβin gastric stomachs. Conclusion It was concluded that ZJP may represents a potential therapeutic option to reduce the risk of gastric ulceration and the gastroprotective activity of ZJP might contribute in adjusting the inflammatory cytokine by regulating the NF-кB signaling pathway. [ABSTRACT FROM AUTHOR]

[Display omitted] • A dry chemical route was designed to prepare CuO/Cu/WO 3−x /WO 3 /W heterostructure. • The structure distribution of the tungsten oxide was measured by Raman technique. • The H+ induced oxygen vacancies in the WO 3−x layer largely narrow the bandgap. • The oxygen vacancies and the Cu species are both beneficial for the charge transfer. Heterostructrural electrocatalysts are promising for enhancing reaction performance by increasing the carriers mobility and lowering the activation energy. Herein, an environmentally friendly dry chemical route based on ion beam technology is designed to construct the heterostructural CuO/Cu/WO 3−x /WO 3 /W electrocatalysts. Through H+ beam bombardment, the oxygen vacancies in the tungsten oxide are created, and the Cu species are deposited simultaneously on the surface oxidized W mesh. This fabrication leads to a significant elevation of HER performance for WO 3 based electrocatalysts. The self-supported CuO/Cu/WO 3−x /WO 3 /W electrode exhibits an overpotential of 127 mV at −10 mA cm−2 in 0.5 M H 2 SO 4 aqueous solution, which is much better than those of the other samples without the WO 3−x layer or the deposited Cu species. The H+ bombardment induced oxygen vacancies enhance the conductivity of the tungsten oxide via narrowing its bandgap, as well as provide large amounts of unsaturated W atoms that could serve as active sites. The Cu species play a role of electron mobility promoter for further enhancing the HER activity. This strategy offers a facile route for the construction of transition metal based heterostructural electrocatalysts. [ABSTRACT FROM AUTHOR]

Sepsis is a cluster of heterogeneous syndromes associated with progressive endotoxemic developments, ultimately leading to damage of multiple organs, including the heart. This study is to investigate the effects of apigenin on heart injury in lipopolysaccharide-induced endotoxemic rat model. Normal Wistar rats were randomly divided into four groups: control group, LPS group (15 mg/kg), LPS plus apigenin groups with different apigenin doses (50 mg/kg, 100 mg/kg). Serum levels of creatine kinase (CK), lactate dehydrogenase (LDH), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β) were measured after the rats were sacrificed. SphK1/S1P signaling pathway proteins, cleaved caspase-3, cleaved caspase-9, Bax and Bcl-2 in heart were measured by Western blot. In vitro, we evaluated the protective effect of apigenin on rat embryonic heart-derived myogenic cell line H9c2 induced by LPS. Apigenin decreased serum levels of CK-MB, LDH, TNF-α, IL-6, IL-1β. SphK1/S1P signaling pathway proteins, cleaved caspase-3, cleaved caspase-9, Bax in heart were found inhibited and Bcl-2 increased in the apigenin groups in vivo. In addition, apigenin inhibited intracellular calcium, the MAPK pathway and SphK1/S1P signaling pathway in vitro. Apigenin exerts pronounced cardioprotection in rats subjected to LPS likely through suppressing myocardial apoptosis and inflammation by inhibiting the SphK1/S1P signaling pathway. [ABSTRACT FROM AUTHOR]

Puerarin is an isoflavonoid isolated from the root of the plant Pueraria lobata and has been used as a prescribed drug in China for the treatment of many diseases in the clinical practice. The present study aimed to determine the protective effects and the underlying mechanisms of puerarin on ovalbumin (OVA)-induced allergic inflammation in a mouse model of allergic asthma. Asthma mice model was established by ovalbumin. A total of 50 mice were randomly assigned to five experimental groups: control, model, dexamethasone (2 mg/kg), and puerarin (10 mg/kg, 20 mg/kg). Airway resistance (Raw) was measured by the forced oscillation technique, differential cell count in BAL fluid (BALF) was measured by Wright–Giemsa staining, histological assessment was measured by hematoxylin and eosin (HE) staining, BALF levels of Th1/Th2 cytokines were measured by enzyme-linked immunosorbent assay, eotaxin-3 was evaluated by western blotting. Our study demonstrated that, compared with model group, puerarin inhibited OVA-induced increases in Raw and eosinophil count; interleukin (IL)-4, IL-5, IL-13 levels were recovered in bronchoalveolar lavage fluid compared; increased IFN-γ level in bronchoalveolar lavage fluid; histological studies demonstrated that puerarin substantially inhibited OVA-induced eosinophilia in lung tissue compared with model group. Western blotting studies demonstrated that puerarin substantially inhibited eotaxin-3 compared with model group. Our findings support puerarin can prevent some signs of allergic asthma in the mouse model. [ABSTRACT FROM AUTHOR]

Highlights: [•] Ovarian cancer cell line HO8910 can better grow on PLGA microspheres. [•] Collagen I coated PLGA microsphere promoted the adhesion and growth of HO8910 cells. [•] HO8910 cells grew on PLGA microspheres increased expression of E-cadherin. [Copyright &y& Elsevier]

Highlights: [•] PU films were modified with PEO by a facile, environment-friendly approach. [•] The hemocompatibility of the PEO-coated PU was significantly improved. [•] PEO-coated PU films were very hydrophilic. [•] The higher molecular weight of PEO shows better hemocompatibility. [ABSTRACT FROM AUTHOR]

Abstract: Automatically learning and grouping key motion patterns in a traffic scene captured by a static camera is a fundamental and challenging task for intelligent video surveillance. To learn motion patterns, trajectory obtained by object tracking is parameterized, and scene image is spatially and evenly divided into multiple regular cell blocks which potentially contain several primary motion patterns. Then, for each block, Gaussian Mixture Model (GMM) is adopted to learn its motion patterns based on the parameters of trajectories. Grouping motion pattern can be done by clustering blocks indirectly, and each cluster of blocks corresponds to a certain motion pattern. For one particular block, each of its motion pattern (Gaussian component) can be viewed as an instance, and all motion patterns (Gaussian components) constitute a bag which can correspond to multiple semantic clusters. Therefore, blocks can be grouped as a Multi-instance Multi-cluster Learning (MIMCL) problem, and a novel Maximum Margin Multi-instance Multi-cluster Learning (M4L) algorithm is proposed. To avoid processing a difficult optimization problem, M4L is further relaxed and solved by making use of a combination of the Cutting Plane method and Constrained Concave–Convex Procedure (CCCP). Extensive experiments are conducted on multiple real world video sequences containing various patterns and the results validate the effectiveness of our proposed approach. [Copyright &y& Elsevier]