Inhibiting MiR-34α reduces retinal cell apoptosis and downstream NF-κB pathway in diabetic retinopathy rats through regulating HMGB1 expression.

BACKGROUND: This is a research aimed to study the effect of micro ribonucleic acid (miR)-34α on the retinal cell apoptosis in diabetic retinopathy (DR) rats and its key molecular mechanism. METHODS: Sprague-Dawley rats were randomly divided into healthy group (H group, N.=5), diabetes group (D group, N.=5), diabetes + negative control transfection group (N group, N.=5) and diabetes + miR-34α inhibitor transfection group (M group, N.=5). The rat model of diabetes was established via intraperitoneal injection of 2% streptozotocin solution (60 mg/kg). After 72 h, the urine glucose and blood glucose were detected, and the urine glucose above 3+ and the blood glucose concentration >16.7 mmol/L indicated the successful modeling. After the rats were normally fed for 4 months, the changes in expression of miR-34α in retinal tissues were detected via reverse transcription-polymerase chain reaction (RT-PCR), the pathological changes in retinal tissues were observed via hematoxylin-eosin (HE) staining, and the retinal cell apoptosis was detected using terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. Moreover, the changes in the number of cells containing active caspase-3 in retinal tissues were determined through immunohistochemistry, and the changes in expressions of caspase-3, high mobility group box 1 (HMGB1) and nuclear factor-κB (NF-κB) in retinal tissues were determined through Western blotting. RESULTS: Compared with those in H group, the cell density declined, and the cells were arranged disorderly with swelling in each retinal layer, the expression of miR-34α in retinal tissues was increased, the retinal cell apoptosis was enhanced, the number of cells containing active caspase-3 in retinal tissues rose, and the expressions of caspase-3, HMGB1 and NF-κB in retinal tissues were increased in D group, N group and M group (P<0.05). Compared with those in D group and N group, the cell density rose, and the cells were arranged less disorderly with milder swelling in each retinal layer, the expression of miR-34α in retinal tissues declined, the retinal cell apoptosis was weakened, the number of cells containing active caspase-3 in retinal tissues was decreased, and the expressions of caspase-3, HMGB1 and NF-κB in retinal tissues were reduced in M group (P<0.05). CONCLUSIONS: Inhibiting miR-34α reduces the retinal cell apoptosis in DR rats through regulating the HMGB1 expression and downstream NF-κB pathway.

A new antibacterial compound from Luo Han Kuo fruit extract (Siraitia grosvenori).

Luo Han Kuo fruit (Siraitia grosvenori Swingle) has been used in China for centuries as a sweetening agent, and also used to treat sore throat and cough. In our recent study, a new bioactive compound, (2R,3S,4S)-2,3-trans-3,4-cis-5,3'-bimethoxy-7-(trans-2-propenal)-3,4-flavandiol (1), named siraitiflavandiol was obtained. The structure has been determined on the basis of spectroscopic studies including 1D and 2D NMR ((1)H, (13)C NMR, (1)H-(1)H COSY, HSQC, HMBC, and NOESY), CD, EI-MS, and HR-EI-MS spectra. The new compound was evaluated in vitro for its inhibitory ability against the growth of oral bacterial species Streptococcus mutans, Porphyromonas gingivalis, and yeast Candida albicans. The minimum inhibitory concentrations were 6, 24, and 6 microg/ml, respectively.