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Objective To investigate the effect of deletion of Sirtuin type 1(Sirt1) gene on liver inflammation of mice and its mechanism. Methods The body weight of C57BL/6J male mice and liver specific Sirt1 deficiency (Sirt1-LKO) male mice were recorded weekly. The sensitivity of inflammatory response was tested by intraperitoneal injection of 20 mg/kg LPS. The survival curve was used to reflect the sensitivity of mice to inflammatory response.The expression of inflammatory factors was detected by Western blot and q-PCR. Results Compared with control wild type mice, Sirt1-LKO mice showed significantly reduced body weight (P＜0.05). In addition, The survival curve was shown by kaplane Meier diagram,Sirt1-LKO mice showed lower sensitivity to LPS (P＜0.05).The protein level of NF-κB in primary liver cells of Sirt1-LKO mice was increased (P＜0.05),Tnfα and IL6 of NF-κB downstream target genes were up-regulated(P＜0.05). Conclusions Hepatocyte-specific Sirt1 deletion aggravates liver inflammation response in mouse model.

Background and Purpose: Neuropathic pain affects millions of patients, but there are currently few viable therapeutic options available. Microtubule affinity‐regulating kinases (MARKs) regulate the dynamics of microtubules and participate in synaptic remodelling. It is unclear whether these changes are involved in the central sensitization of neuropathic pain. This study examined the role of MARK1 or MARK2 in regulating neurosynaptic plasticity induced by neuropathic pain. Experimental Approach: A rat spinal nerve ligation (SNL) model was established to induce neuropathic pain. The role of MARKs in nociceptive regulation was assessed by genetically knocking down MARK1 or MARK2 in amygdala and systemic administration of PCC0105003, a novel small molecule MARK inhibitor. Cognitive function, anxiety‐like behaviours and motor coordination capability were also examined in SNL rats. Synaptic remodelling‐associated signalling changes were detected with electrophysiological recording, Golgi‐Cox staining, western blotting and qRT‐PCR. Key Results: MARK1 and MARK2 expression levels in amygdala and spinal dorsal horn were elevated in SNL rats. MARK1 or MARK2 knockdown in amygdala and PCC0105003 treatment partially attenuated pain‐like behaviours along with improving cognitive deficit, anxiogenic‐like behaviours and motor coordination in SNL rats. Inhibition of MARKs signalling reversed synaptic plasticity at the functional and structural levels by suppressing NR2B/GluR1 and EB3/Drebrin signalling pathways both in amygdala and spinal dorsal horn. Conclusion and Implications: These results suggest that MARKs‐mediated synaptic remodelling plays a key role in the pathogenesis of neuropathic pain and that pharmacological inhibitors of MARKs such as PCC0105003 could represent a novel therapeutic strategy for the management of neuropathic pain. [ABSTRACT FROM AUTHOR]

Objective To explore the effect of barley plus butter dietary on the symptoms of dextran sodium sulfate induced chronic ulcerative colitis and intestinal microbial distribution in mice. Methods In customized feed(C feed), soybean oil and corn meal in standard mice breeding feed (N feed) were replaced with equal proportion of ghee and raw barley powder.28 male mice were randomly divided into 4 groups(n=7,each group):NW group fed with N feed and water; ND group fed with N feed and 1.8% DSS; CW group fed with C feed and water; CD group fed with C feed and 1.8% DSS. Colitis model was established by three cycles of 10 days supply of distilled water after 7 days supply of 1.8% DSS solution. Finally, the effects were evaluated by DAI score, colon HE staining and 16S rRNA high-throughput sequencing of gut microbes. Results The abundance of bacteria was increased and the diversity of intestinal flora, such as allobaculum, was improved in wild type mice fed on the barley and butter dietary. However, when the mice were treated with DSS, the barley plus butter dietary group had high DAI score(P＜0.05), showed obvious intestinal ulcers and disorganized intestinal glands by histopathological microscopy, and decreased intestinal flora abundance and diversity(P＜0.05). But the quantity of Clostridium and Sartreella was increased in barley and butter dietary group(P＜0.05). Conclusions The barley plus butter dietary increases intestinal flora Allobaculum of wild type mice and improves the composition of intestinal flora, but the dietary intervention fails to show any significant impact on the chronic ulcerative colitis symptoms induced by DSS.

Objective To observe the changes of insulin sensitivity of flavonoids 4, 4'-dimethoxy chalcone (DMC) in mice fed on high-fat diet (HFD) and to investigate its effect. Methods Wild-type C57/BL 6 mice fed on HFD were divided into control group and experimental group. DMC and solvent DMSO were injected intraperitoneally at 3 μg/kg every other day. Food intake and body weight of the two groups were recorded weekly, glucose tolerance test (GTT), insulin tolerance test (ITT) and sodium pyruvate tolerance test(PTT) were measured at week 6. The adipose tissues were examined by immunohistochemistry and HE staining. Results Compared with the control mice, the mice treated with DMC drug was no different in body weight and food intake. ITT indicated that DMC administration increased insulin sensitivity (P＜0.05), but GTT and PTT showed no significant difference. HE staining microscopy showed that adipose tissue contained less mononuclear cells in mice treated with DMC than control mice. There was weak staining for F4/80 in the adipose tissue of mice treated with DMC, defined as F4/80-positive cells. Conclusions DMC can improve the insulin sensitivity of mice in high-fat diet by decreasing the infiltration of macrophages in adipose tissue.

Using the first-principles exact muffin-tin orbital method in combination with the coherent potential approximation, the crystal structure and site preference, magnetic and elastic properties, and martensitic transformation (MT) are systematically investigated with the three groups of Heusler alloys: (Co 2 − x M x)VGa (M1 x), Co 2 (V 1 − x M x)Ga (M2 x), and Co 2 V(Ga 1 − x M x) (M3 x , M = Ni and Fe, 0 ≤ x ≤ 1.0). It is shown that instead of the L 2 1 and X A structures, the fcc one is energetically preferred in the cubic M3x (x ≥ 0.8) alloys. In L 2 1 -Ni2x (x ≤ 0.6) and fcc-Ni3x (x = 0.8), Ni atoms even prefer the Ga and Co anti-sites, respectively, and the replaced atoms move to the sublattices of the deficient ones. Their total magnetic moment is dominated by the magnetic exchange interactions corresponding to the pairs of two Co atoms on the different sublattices in M = Ni and Fe1x, Co and Fe in Fe2x and Fe3x (x < 0.8), and Fe and Fe atoms in Fe3x (x ≥ 0.8) alloys, respectively. These Ni1x, Ni2x, and Fe3x with x ≥ 0.4 as well as Ni3x with x ≥ 0.2 alloys are predicted having the MT behavior and also the better mechanical property relative to Co 2 VGa. A lower shear modulus (C ′ = (C 11 − C 12) / 2) generally corresponds to a higher MT temperature, and these alloys, which can undergo the MT are further evaluated with C ′ < 36.50 GPa. Both considerable magnetocaloric and magnetovolume effects can be also expected during the MT of these Fe3x alloys (x = 0.4 and 0.6). In the remaining Fe1x and Fe2x alloys, the Fe doping disfavors the MT and also improves their brittleness. The structural preference of these cubic alloys and also their stability relative to the tetragonal martensite can be mainly attributed to the number of their minority density of states at the Fermi level: the smaller they are, the more stable their system tends to be. [ABSTRACT FROM AUTHOR]

Objective To investigate the role of mammalian sterile line 20-like kinas 1(MST1) and its regulatory mechanism in hepatic gluconeogenesis of mouse. Methods The mRNA expression of MST1 in the liver of db/db mice and db/m mice was detected by RT-qPCR. MST1 was overexpressed with adenovirus to detect glucose output capacity in mouse primary hepatocytes. Luciferase reporter assay was adopted to detect the effect of MST1 on phosphoenolpyruvate carboxykinase (PEPCK) promoter activity in HepG2 cells. Forkhead transcription factor O1 (FOXO1) was knocked down by interfering adenovirus in primary mouse liver cells to detect the effect of MST1 overexpression on the mRNA levels of PEPCK. Results The mRNA level of MST1 was significantly upregulated in the liver of db/db mice (P＜0.001). MST1 overexpression enhanced glucose output in mouse primary hepatocytes (P＜0.05). In HepG2 cells, MST1 overexpression increased the mRNA of PEPCK (P＜0.001) and the activity of PEPCK promoter (P＜0.01). Furthermore, MST1-induced increase in PEPCK mRNA was abolished when FOXO1 was knocked down by interfering adenovirus. Conclusions MST1 promotes hepatic gluconeogenesis by regulating the mRNA expression of PEPCK dependent on FOXO1.