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Objective: To discover the expression pattern and potential underlying mechanism of the caspase recruitment domain‐containing protein 9 (CARD9) in oral squamous cell carcinoma (OSCC). Methods: Caspase recruitment domain‐containing protein 9 expression was detected by qRT‐PCR and Western blot in OSCC tissues and cells, and OSCC (CGHNC9 and OECM‐1) cell lines were divided into control, NC siRNA, and CARD9 siRNA groups. Then, MTT, flow cytometry, wound‐healing, and Transwell assays were carried out to determine the changes in cellular biological characteristics. Immunoblot assay was performed for the expressions of NF‐κB pathway. Finally, we constructed the xenograft models in nude mice to validate the in vivo effect of CARD9 siRNA on OSCC cell growth. Results: Caspase recruitment domain‐containing protein 9 was upregulated in both OSCC tissues and cells, exhibiting a close relation with major clinicopathological features of OSCC patients. Transfection of CARD9 siRNA inhibited the proliferation, migration, and invasion of OSCC cells with the enhanced cell apoptosis, and meanwhile, CARD9, p‐p65/p65, p‐IKKα/IKKα, and p‐IkBα/IkBα were downregulated. The tumor formation assay on nude mice also suggested that CARD9 siRNA might block the in vivo growth of OSCC cells. Conclusion: Caspase recruitment domain‐containing protein 9 suppression results in the upregulation of NF‐κB pathway with suppressed proliferation, migration, and invasion of OSCC cells and facilitates the apoptosis. [ABSTRACT FROM AUTHOR]

The main clinical manifestations of eczema include itching, erythema, swelling and pain. Currently, allergies and TH1/TH2 cytokine imbalances are significant causes of eczema. TCM believes that eczema is mainly caused by incongruity between dry and wet. Wenguanmu ointment is a classic Mongolian medicine, which mainly composed of Xanthoceras sorbifolia Bunge , Coptis chinensis Franch and Bezoar. These ingredients can clear heat and dampness, dispel wind and dehumidification, anti-inflammatoryad analgesic. In this study, it was found that Wenguanmu ointment can treat eczema with anti-inflammatory, analgesic and antipruritic. In this study, the content of main components in Wenguanmu ointment was tested. Moreover, the therapeutic effect and mechanism of Wenguanmu ointment on eczema model mice were studied. Kunming mice (25 ± 2 g) were randomly divided into 6 groups: Control group; Model group; Vehicle group; Wenguanmu ointment group; Compound dexamethasone acetate cream group; Chushizhiyang ointment group. The eczema mouse model was established by DNCB. HPLC and TLC tests were used to determine the content of the main components in Wenguanmu ointment. HE staining was used to assess skin damage in mice. In order to detect the anti-inflammatory effect of Wenguanmu ointment on eczema, The levels of IgE, TNF-α, IFN-γ, COX-2 and IL-4 in serum was measured by ELISA. Genecards and Online Mendelian Inheritance in Man databases were used to analyze potential target gene predictions, and it was speculated that Wenguanmu ointment was associated with NF−κB signaling pathway and chemokine signaling pathway. To detect this inference, RT-qPCR and western blotting were used to detect protein and mRNA levels of CKLF-1, IκB-α, and NF-κB. Wenguanmu ointment can repress the symptoms of eczema caused by 2, 4-dinitrochlorobenzene, and inhibit the level of serum immunoglobulin E. Simultaneously it restrain the elevation of miscellaneous pro-inflammatory cytokines and chemokines, as well as reducing the expression of CKLF-1 and NF-κB protein in the nucleus, and increasing the protein expression of IκB to improve eczema. The ameliorating effect of Wenguanmu ointment on eczema lesions can play a importment role by inhibiting the CKLF-1/NF-κB pathway. [Display omitted] [ABSTRACT FROM AUTHOR]

A hepatitis B virus (HBV) transgenic mice model was used to establish the fatty liver superimposed model by feeding the methionine choline-deficient (MCD) diet for 8 weeks, with or without the gavage of 2 mg/kg zeaxanthin dipalmitate (ZD) three times per week. Both wild-type and HBV transgenic mice, with MCD diet, gained typical non-obese non-alcoholic steatohepatitis (NASH) and HBV symptoms. Coadministration with ZD exhibited evident therapeutic effects through alleviating those pathological events. Moreover, long-term vehicle-ZD treatment was found to be safe. Thus, ZD is a promising and safe hepato-protective agent against hepatic injury induced by superimposed HBV and NASH in non-obese mice. [ABSTRACT FROM AUTHOR]

In order to find potential agents for treating cancer disease in naturally occurring compounds, we conducted a systematic phytochemical investigation on the endemic species of Garcinia nujiangensis. Three new biphenyl derivatives (1–3) and one new polycyclic polyprenylated benzophenone (4), together with four known benzophenone analogues (5 – 8), have been isolated from the CH 2 Cl 2 extract of the twigs and leaves of G. nujiangensis. Their structures were determined by detailed spectroscopic analyses and comparison with structurally related known analogues. Experimental and calculated ECD method was used to determine the absolute configuration of 1 and 4. Moreover, compounds 5 – 7 were isolated for the first time from this species. The cytotoxicities of the new compounds were evaluated using HL-60, HepG2, and A549 human cancer cell lines. Compound 4 showed more significant antiproliferative effects against HepG2 cells with an IC 50 value of 11.38 ± 0.79 μM than that of three biphenyl derivatives. The morphological features of apoptosis were evaluated in 4 -treated HepG2 cells. Compound 4 effectively prevented the cell cycle progression of HepG2 cells in G 2 phase. Additionally, western blot analysis indicated that treatment of 4 on HepG2 cells led to decreased expression of anti-apoptotic Bcl-2 and pro-Caspase-3, and increased protein expression of both pro-apoptotic Bax and cleaved PARP with reference to β -actin. Overall, our results suggested that the active polycyclic polyprenylated benzophenone derivatives in the twigs and leaves of G. nujiangensis can be used as a valuable source of bioactive compounds for the pharmaceutical industry. [Display omitted] • Three new biphenyl derivatives and one new benzophenone were isolated from the twigs and leaves of G. nujiangensis. • Experimental and calculated ECD method was used to determine the absolute configuration of 1 and 4. • 4 showed more significant antiproliferative effects against HepG2 cells with an IC 50 value of 11.38 ± 0.79 μM. • 4 effectively prevented the cell cycle progression of HepG2 cells in G 2 phase. • Western blot analysis showed that 4 mediated apoptosis of HepG2 cells by both extrinsic and intrinsic apoptotic pathways. [ABSTRACT FROM AUTHOR]

Purpose: We aim to examine whether honey ameliorates hepatic injury in non-alcoholic steatohepatitis (NASH) animal and cell line steatosis models. Methods: NASH was induced in female Sprague-Dawley rat by 8-week feeding with a high-fat diet. During the experiment, 5 g/kg honey was intragastrically fed daily. Rat normal hepatocyte BRL-3A cell was treated with sodium palmitate (SP) to induce steatosis in the absence or presence of honey pre-treatment or specific siRNA/overexpress plasmid of thioredoxin-interacting protein (TXNIP) or antagonist/agonist of Nod-like receptor protein 3 (NLRP3). Results: Honey significantly improved the high-fat-diet-induced hepatic injury, steatosis, fibrosis, oxidative stress, and inflammation in rats. Honey also inhibited the overexpression of TXNIP and the activation of NLRP3 inflammasome. These effects were replicated in BRL-3A cell line which showed that the down-regulation of TXNIP or inhibition of NLRP3 contributed to the suppression of NLRP3 inflammasome activation, inflammation, and re-balanced lipid metabolism. In contrast, overexpression of TXNIP or agonism of NLRP3 exacerbated the cellular damage induced by SP. Conclusion: Suppression of the TXNIP-NLRP3 inflammasome pathway may partly contribute to the amelioration of hepatic injury during the progression of NASH by honey. Targeting hepatic TXNIP-NLRP3 inflammasome pathway is a potential therapeutic way for the prevention and treatment of NASH. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the protective mechanisms of an 85 % pure extract of (−) epigallocatechin gallate (EGCG) in the development of fibrosis, oxidative stress and inflammation in a recently developed dietary-induced animal model of non-alcoholic fatty liver disease (NAFLD). Methods: Female Sprague-Dawley rats were fed with either normal rat diet or high-fat diet for 8 weeks to develop NAFLD. For both treatments, rats were treated with or without EGCG (50 mg/kg, i.p. injection, 3 times per week). At the end, blood and liver tissue samples were obtained for histology, molecular, and biochemical analyses. Results: Non-alcoholic fatty liver disease (NAFLD) rats showed significant amount of fatty infiltration, necrosis, fibrosis, and inflammation. This was accompanied by a significant expressional increase in markers for fibrosis, oxidative stress, and inflammation. TGF/SMAD, PI3 K/Akt/FoxO1, and NF-κB pathways were also activated. Treatment with EGCG improved hepatic histology (decreased number of fatty score, necrosis, and inflammatory foci), reduced liver injury (from ~0.5 to ~0.3 of ALT/AST ratio), attenuated hepatic changes including fibrosis (reduction in Sirius Red and synaptophysin-positive stain) with down-regulation in the expressions of key pathological oxidative (e.g. nitrotyrosine formation) and pro-inflammatory markers (e.g. iNOS, COX-2, and TNF-α). EGCG treatment also counteracted the activity of TGF/SMAD, PI3 K/Akt/FoxO1, and NF-κB pathways. Treatment with EGCG did not affect the healthy rats. Conclusions: Epigallocatechin gallate (EGCG) reduced the severity of liver injury in an experimental model of NAFLD associated with lower concentration of pro-fibrogenic, oxidative stress, and pro-inflammatory mediators partly through modulating the activities of TGF/SMAD, PI3 K/Akt/FoxO1, and NF-κB pathways. Therefore, green tea polyphenols and EGCG are useful supplements in the prevention of NAFLD. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the hepato-protective properties and underlying mechanisms of SAMC in a non-alcoholic fatty liver disease (NAFLD) rat model. Methods: Female rats were fed with a diet comprising highly unsaturated fat diet (30% fish oil) for 8 weeks to develop NAFLD with or without an intraperitoneal injection of 200 mg/kg SAMC three times per week. After euthanasia, blood and liver samples of rats were collected for histological and biochemical analyses. Results: Co-treatment of SAMC attenuated NAFLD-induced liver injury, fat accumulation, collagen formation and free fatty acids (FFAs). At the molecular level, SAMC decreased the lipogenesis marker and restored the lipolysis marker. SAMC also reduced the expression levels of pro-fibrogenic factors and diminished liver oxidative stress partly through the inhibition in the activity of cytochrome P450 2E1-dependent pathway. NAFLD-induced inflammation was also partially mitigated by SAMC treatment via reduction in the pro-inflammatory mediators, chemokines and suppressor of cytokine signaling. The protective effect of SAMC is also shown partly through the restoration of altered phosphorylation status of FFAs-dependent MAP kinase pathways and diminished in the nuclear transcription factors (NF-κB and AP-1) activity during NAFLD development. Conclusions: SAMC is a novel hepato-protective agent against NAFLD caused by abnormal liver functions. Garlic or garlic derivatives could be considered as a potent food supplement in the prevention of fatty liver disease. [ABSTRACT FROM AUTHOR]

Purpose: To study the protective effects and underlying molecular mechanisms of SAMC on carbon tetrachloride (CCl)-induced acute hepatotoxicity in the mouse model. Methods: Mice were intraperitoneally injected with CCl (50 μl/kg; single dose) to induce acute hepatotoxicity with or without a 2-h pre-treatment of SAMC intraperitoneal injection (200 mg/kg; single dose). After 8 h, the blood serum and liver samples of mice were collected and subjected to measurements of histological and molecular parameters of hepatotoxicity. Results: SAMC reduced CCl-triggered cellular necrosis and inflammation in the liver under histological analysis. Since co-treatment of SAMC and CCl enhanced the expressions of antioxidant enzymes, reduced the nitric oxide (NO)-dependent oxidative stress, and inhibited lipid peroxidation induced by CCl. SAMC played an essential antioxidative role during CCl-induced hepatotoxicity. Administration of SAMC also ameliorated hepatic inflammation induced by CCl via inhibiting the activity of NF-κB subunits p50 and p65, thus reducing the expressions of pro-inflammatory cytokines, mediators, and chemokines, as well as promoting pro-regenerative factors at both transcriptional and translational levels. Conclusions: Our results indicate that SAMC mitigates cellular damage, oxidative stress, and inflammation in CCl-induced acute hepatotoxicity mouse model through regulation of NF-κB. Garlic or garlic derivatives may therefore be a potential food supplement in the prevention of liver damage. [ABSTRACT FROM AUTHOR]

Abstract: We investigated the protective effects of two non-steroid anti-inflammatory drugs, indomethacin (COX-1 and COX-2 inhibitors) and nimesulide (specific COX-2 inhibitor) on the hepatic injury induced by lipopolysaccharide in d-galactosamine sensitized (Gal/LPS) mice. ICR male mice were injected with a single dose of Gal/LPS with or without pre-treatment of 3mg/kg indomethacin or 30mg/kg nimesulide (single i.p. injection). Sixteen hours later, blood and liver tissues of mice were collected for histological, molecular, and biochemical analyses. Our results showed marked reduction of hepatic necrosis, serum ALT, and tissue TBARS levels in both indomethacin- and nimesulide-pre-treated mice when compared with Gal/LPS-treated mice. Western blot and RT-PCR analysis showed decreased levels of iNOS mRNA, iNOS protein, and nitrotyrosine formation in both COX inhibitor pre-treated groups when compared with Gal/LPS-treated group. There was an inverse relationship between COX-1 and COX-2 expressions, as well as between COX-2 and C/EBP-α expressions in COX inhibitors groups, Gal/LPS and control groups. COX inhibitors reduced the expression of TNF-α mRNA and the activity of NF-κB which were elevated by Gal/LPS treatment. We conclude that COX inhibitors protected the liver from Gal/LPS-induced hepatotoxicity. COX inhibitors could be considered as potential agents in the prevention of acute liver failure and sepsis. [Copyright &y& Elsevier]

• MiR-18b was downregulated in cerebral ischemic/reperfusion injury. • MiR-18b restoration attenuated cerebral ischemic/reperfusion injury. • MiR-18b restoration protected against ischemic/reperfusion injury through PI3K/Akt signaling pathway by inhibiting ANXA3. Recent, research has displayed that the disorders of miR-18b are related to ischemic stroke. Here, we aimed to investigate the underlying neuroprotective mechanism of miR-18b in cerebral ischemia/reperfusion (I/R) injury. Oxygen-glucose deprivation/reperfusion (OGDR) model in vitro and middle cerebral artery occlusion (MCAO) model in vi vo were established to simulate cerebral I/R injury. RT-PCR, western blotting, CCK-8, TUNEL, and TTC staining assays were applied in this study to explore the effect of miR-18b on cerebral I/R injury. Results displayed that miR-18b expression was reduced after cerebral I/R injury. Besides, miR-18b showed neuroprotective effects on cerebral I/R injury both in vitro and in vivo , These neuroprotective effects included promoting cell viability, decreasing cell apoptosis, reducing the production of inflammatory cytokines in SH-SY 5Y cells after OGDR and depressing MCAO-induced infarct size, neurological deficits and apoptotic cells in mice. Moreover, miR-18b negatively regulated ANXA3 expression, and its neuroprotection on cerebral I/R injury was overturned by ANXA3. Additionally, increasing miR-18b or decreasing ANXA3 promoted the activation of the PI3K/Akt signaling pathway in SH-SY 5Y cells after cerebral I/R injury. In conclusion, these data indicate that miR-18b protects against cerebral I/R injury by inhibiting ANXA3 and activating PI3K/Akt pathway, which provides a promising therapeutic target for ischemic stroke therapy. [ABSTRACT FROM AUTHOR]