Lsd1 inhibitor treatment also blocked Slug-stimulated lipogenesis. Remarkably, hepatocyte-specific deletion of Slug inhibited the hepatic lipogenic program and protected against obesity-associated NAFLD, insulin resistance, and glucose intolerance in mice. Conversely, liver-restricted overexpression of Slug, but not the Lsd1 binding-defective Slug mutant, had the opposite effects. These results unveil an insulin/Slug/Lsd1/H3K9 demethylation lipogenic pathway that promotes NAFLD and type 2 diabetes.Honokiol is a natural active compound extracted from Chinese herbal medicine, Magnolia officinalis. In this study, the role of honokiol in the development of carotid artery atherosclerotic lesions was evaluated in an ApoE-/- mouse model fed with a normal diet (ND) or a Western-type diet (WD) for ten weeks. P7C3 cell line After first two weeks, a perivascular collar was surgically placed on the right common carotid arteries of the mice. Then, WD-fed mice were intraperitoneally injected with honokiol (10 or 20 mg/kg) or administrated with 10 mg/kg atorvastatin calcium by gavage once a day for eight weeks. After that, the right common carotid arteries were excised for further experiments. The result showed that honokiol substantially inhibited the development of atherosclerotic lesions. Furthermore, honokiol downregulated the expression of pro-inflammatory markers, like tumor necrosis factor-α, interleukin (IL)-6, and IL-1β. Additionally, honokiol treatment decreased reactive oxygen species level and enhanced superoxide dismutase activity. Nitric oxide level, inducible nitric oxide synthase (iNOS) expression, and aberrant activation of nuclear factor-κB pathway were also significantly inhibited by honokiol treatment. Together, these findings suggest that honokiol protects against atherosclerotic plaque formation in carotid artery, and may be an effective drug candidate for the treatment of carotid artery atherosclerotic stenosis.There are many reports about natural products relieving neuralgia. Osthole is the main component of Angelica biserrata Yuan et Shan, a natural product that treats rheumatism through the elimination of inflammation and the alleviation of pain that has a long history in the clinic. The analgesic mechanism of osthole is complicated and confusing. Astrocytes have attracted increasing attention from pain researchers. Inhibitors targeting astrocytes are thought to be promising treatments for neuropathic pain. Whether osthole can alleviate neuropathic pain through astrocytes has not been elucidated in detail. In this study, CCI surgery was used to establish the neuropathic pain model in mice. The CCI mice were treated with osthole (5, 10, or 20 mg/kg/day) for 14 days in vivo. Mechanical allodynia and heat hyperalgesia were measured to evaluate the therapeutic effect of osthole. In mechanism research, the activation of astrocytes; the protein expression of P2Y1R and p-JNK in astrocytes; the release of inflammatory fasthole alleviates neuropathic pain in mice via the P2Y1-receptor-dependent JNK signaling pathway in spinal astrocytes, and osthole could be considered a potential pharmacotherapy to alleviate neuropathic pain.OBJECTIVE Aimed to find the cut-off point of handgrip strength and it’s association with MetS. RESULTS The relative handgrip strength was negatively associated with the prevalence of MetS. Of note, the odds ratios (ORs) with 95% confidence intervals (CIs) across tertiles of relative handgrip strength were 1 (reference), 0.45 (0.33, 0.62), and 0.13 (0.08, 0.20) in male participants after adjusting for demographic factors, calorie intake, and physical activity. Similar results were observed in female participants. The cutoff values of relative handgrip strength for male and female participants were 0.52 and 0.40, respectively. CONCLUSIONS Findings of this study suggest that a strong relationship exists between handgrip strength and prevalence of MetS in US adults, regardless of sex. METHODS A total of 5 056 participants in the National Health and Nutrition Examination Survey were analysed in this study. Handgrip strength was measured by using a handgrip dynamometer. MetS was defined in accordance with the criteria of the scientific statement of the American Heart Association in 2009. Multivariable binary logistic regression was used to explore the association between handgrip strength and MetS.Methyltransferase-like protein 3 (METTL3) regulates multiple cell functions and diseases by modulating N6-methyladenosine (m6A) modifications. However, it is still unclear whether METTL3 involves in the pathogenesis of diabetic retinopathy (DR). In the present study, we found that high-glucose inhibited RPE cell proliferation, promoted cell apoptosis and pyroptosis in a time-dependent manner. In addition, both METTL3 mRNA and miR-25-3p were low-expressed in the peripheral venous blood samples of diabetes mellitus (DM) patients compared to normal volunteers, and high-glucose inhibited METTL3 and miR-25-3p expressions in RPE cells. As expected, upregulation of METTL3 and miR-25-3p alleviated the cytotoxic effects of high-glucose on RPE cells, and knock-down of METTL3 and miR-25-3p had opposite effects. Additionally, METTL3 overexpression increased miR-25-3p levels in RPE cells in a microprocessor protein DGCR8-dependent manner, and miR-25-3p ablation abrogated the effects of overexpressed METTL3 on cell functions in high-glucose treated RPE cells. Furthermore, PTEN could be negatively regulated by miR-25-3p, and overexpression of METTL3 increased phosphorylated Akt (p-Akt) levels by targeting miR-25-3p/PTEN axis. Consistently, upregulation of PTEN abrogated the protective effects of METTL3 overexpression on RPE cells treated with high-glucose. Collectively, METTL3 rescued cell viability in high-glucose treated RPE cells by targeting miR-25-3p/PTEN/Akt signaling cascade.in English, Hungarian Az otosclerosis egy komplex csontremodellinggel járó multifaktoriális, humánspecifikus fülbetegség. A csontos labyrinthust érinti, aminek következtében típusosan a stapes rögzül az ovális ablakban. A betegség során kialakult hallócsontláncolati fixatio által csökken a középfül akusztikusimpedancia-illesztő, -erősítő funkciója, így jellemzően vezetéses típusú halláscsökkenés jön létre. A halláscsökkenés progresszív, a későbbiekben a belső fül érintettségének jeleként sensorineuralis komponenssel egészül ki. Mindezen folyamat egy időben elvégzett hallásjavító műtéttel megelőzhető vagy jelentősen lassítható. A stapessebészet fejlődése átíveli a XX. századot, és bár a főbb, Shea és Marquet által már az 1960-as években lefektetett műtéti lépések meglehetősen konzervatívak, finom módosítások, elsősorban a technikai fejlődésnek köszönhetően, még ma is folyamatosan történnek. Számos tanulmány igazolja, hogy otosclerosisban továbbra is a stapedotomia az elsőként választandó terápiás eljárás. Megfelelő műtéti technikával a légvezetéses hallásban jelentős javulás érhető el, a beszédfrekvenciákon a csont–lég-köz minimalizálható, illetve zárható, ami a betegek életminőségét jelentősen javítja.