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Recently, the role of gut microbiota in the development of obesity and type 2 diabetes mellitus (T2DM) has been highlighted. We performed an 8-week administration protocol on T2DM (C57BL/6J db-/db-) mice and fecal samples were collected. Comparisons of fecal bacterial communities were performed between db-/db- mice and normal mice (DB/DB) and between the db-/db mice treated and untreated with AOE using next-generation sequencing technology. Our results showed that the db-/db-AOE group had improved glycemic control and renal function compared with the db-/db-H2O group. Compared with the db-/db-H2O group, AOE administration resulted in significantly increased ratio of Bacteroidetes-to-Firmicutes in db-/db- mice. In addition, the abundance of Akkermansia was significantly increased, while Helicobacter was significantly suppressed in the db-/db-AOE group compared with the db-/db-H2O group. Our data suggest that AOE treatment decreased blood glucose levels and significantly reduced damage of renal pathology in the T2DM mice by modulating gut microbiota composition.

MiR-223-5p has been demonstrated to regulate the development and progression of various cancers, such as hepatocellularcarcinoma, breast cancer and gastric carcinoma. However, the role of miR-223-5p in non-small cell lung cancer (NSCLC) requires further investigation. In this study, we found that the expression of miR-223-5p was significantly down-regulated in NSCLC tissues and cell lines. Moreover, the expression level of miR223-5p is negatively correlated with the malignance of NSCLC. Besides, we found that overexpression of miR-223-5p remarkably suppressed the proliferation of NSCLC cells and. MiR-223-5p overexpression also led to reduced migration and invasion in NSCLC cells. Mechanistically, we found that E2F8, a key transcription factor involved in many kinds of biological processes, was a direct target gene of miR-223-5p. Overexpression of miR-223-5p significantly decreased the mRNA and protein levels of E2F8 in NSCLC cells. What's more, we showed that restoration of E2F8 rescued the proliferation, migration and invasion of miR-223-5p-overexpressing NSCLC cells. Taken together, our findings demonstrated that miR-223-5p suppressed NSCLC progression through targeting E2F8.

BackgroundThe objective of the present study was to investigate the effectiveness of acidic fibroblast growth factor delivered in collagen (aFGF/collagen) for promoting tendon–bone interface healing after anterior cruciate ligament (ACL) reconstruction in rabbits.MethodsACL reconstructions were performed in the right hind limbs of New Zealand rabbits. Each left long digital extensor tendon was harvested as an autograft, and collagen incorporating different concentrations of aFGF or same amount of collagen alone was applied at the tendon–bone interface after ACL reconstruction. The control group underwent ACL reconstruction only. There were high and low aFGF/collagen groups, collagen alone group, and control group (n = 21 rabbits per group). Histological and biomechanical analyses were performed at 4, 8, and 12 weeks postoperatively to evaluate the effect of aFGF/collagen on tendon–bone interface healing.ResultsResults of biomechanical tests showed that at both 8 and 12 weeks postoperatively, the elastic modulus and stiffness in both the high and low aFGF/collagen treatment groups were significantly higher than those in the control group and collagen alone group, with that in the high aFGF/collagen concentration group being the highest. Histological analysis showed that at 8 weeks, tightly organized Sharpey-like fibers were observed in both aFGF/collagen groups with new bone growth into the tendon in the high concentration group. At 12 weeks postoperatively, a fibrocartilage transition zone was observed in the bone tunnels in both aFGF/collagen groups, especially in the high aFGF/collagen group.ConclusionApplication of the aFGF/collagen composite could enhance early healing at the tendon–bone interface after ACL reconstruction, especially with the use of a high aFGF/collagen concentration.

Background/Aims: The purpose of our experiments was to investigate the targeting relationship of linc00515, miR-140-5p and ATG14 and to explore the roles of linc00515, miR-140-5p and ATG14 in autophagy and chemoresistance of melphalan-resistant multiple myeloma cells. Methods: Plasmids that could interfere with the expression of linc00515 and ATG14 were loaded into myeloma cells, which were cultured with melphalan. MTT assay and flow cytometry analysis were utilized to investigate the effect of linc00515, miR-140-5p and ATG14 on the resistance of myeloma cells. QRT-PCR was used to determine the levels of mRNAs. Western blot was utilized to explore the level of ATG14 and autophagy-related proteins. Dual luciferase assay was utilized to explore the targeting relationship between linc00515, miR-140-5p and ATG14. GFP LC3 fluorescence assay was conducted to study the autophagy of cells. Results: The expression of linc00515 and ATG14 were significantly higher in melphalan-resistant myeloma cells. Knockdown of linc00515 and ATG14 led to decreased autophagy and chemoresistance of melphalan-resistant myeloma cells. The forced expression of miR-140-5p suppressed autophagy and chemoresistance of melphalan-resistant myeloma cells. Conclusion: Linc00515 enhanced autophagy and chemoresistance of melphalan-resistant myeloma by directly inhibiting miR-140-5p, which elevated ATG14 level.

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The aim of the present study was to observe the dynamic changes of the growth arrest and DNA damage-inducible 153 (GADD153) gene and caspase-12 in the brain tissue of rats with cerebral ischemia-reperfusion injury (CIRI) and the impact of curcumin pretreatment. A total of 60 rats were randomly divided into the normal group (N), the sham operation group (S), the dimethyl sulfoxide control group (D) and the curcumin treatment group (C). For group D and C, 12 (T1), 24 (T2) and 72 h (T3) of reperfusion were performed after 2 h ischemia. The expression levels of GADD153 and caspase-12 in the brain tissue were detected and compared among the groups by immunohistochemistry, immunofluorescence double staining and western blotting. The expression levels of GADD153 and caspase-12 were increased at T1compared with groups N and S, and the expression of caspase-12 peaked at T2 in group D, while GADD153 was increased until T3 in group D. Compared with group D, the expression levels of GADD153 and caspase-12 in group C at T2 and T3 were significantly decreased (P<0.05). Endoplasmic reticulum stress is involved in the pathological process of CIRI. Curcumin may decrease the expression levels of the above two factors, thus exhibiting protective effects against CIRI in rats.

Diabetes mellitus is characterized by high blood glucose levels. Increased levels of reactive oxygen species (ROS) may disrupt insulin signaling and result in insulin resistance. The Alpinia oxyphylla extract (AOE) possesses powerful antioxidant activity and may therefore inhibit the development of insulin resistance. The objective of the present study was to determine the effects of AOE on blood glucose, insulin and lipid levels in a type II diabetic nephropathy animal model (C57BIKsj db-/db-). All experiments were performed on male C57BL/Ks DB/DB and db-/db- mice that were left to acclimatize for 1 week prior to the experimental period. AOE was administered to these mice at different dosages (100, 300 and 500 mg/kg) for 8 weeks. The results demonstrated that AOE did not affect mouse weight, while blood glucose concentrations were found to significantly decrease in a dose-dependent manner (P<0.05). The effect of administering 500 mg/kg AOE (AOE500) to db-/db- mice was tested further. Treatment with AOE500 for 8 weeks led to improved glucose tolerance and reduced plasma insulin concentrations (P<0.05), as well as a significant decrease in triglyceride concentrations (P<0.05) and levels of total cholesterol (P<0.05) in db-/db- mice. Furthermore, treatment with AOE500 decreased the concentration of malondialdehyde, elevated the concentration of glutathione and increased the activities of the antioxidant enzymes superoxide dismutase and peroxidase (P<0.05) in the livers of db-/db- mice. Meanwhile, AOE-treated mice exhibited significantly reduced urine albumin, creatinine and blood urea nitrogen excretion (P<0.05). In parallel, the upregulated expression of phosphatase and tensin homolog (PTEN) in the liver and kidneys of db-/db- mice was impaired following AOE500 treatment. The results of the present study suggest that AOE regulates blood glucose and lipid levels and improves renal function by mediating oxidative stress and PTEN expression at the onset of type II diabetes mellitus.