ABSTRACT
Alcoholic liver disease(ALD), with its increasing morbidity and mortality, has seriously and extensively affected the health of people worldwide. Methyl ferulic acid(MFA) has been proven to significantly inhibit alcohol-induced lipid production in L02 cells through the AMP-activated protein kinase(AMPK) pathway, but its in-depth mechanism remains unclear. This study aimed to further clarify the mechanism of MFA in improving lipid accumulation in L02 cells through the microRNA-378b(miR-378b)-mediated calcium/calmodulin-dependent protein kinase kinase 2(CaMKK2)-AMPK signaling pathway based on existing researches. L02 cells were induced by 100 mmol·L~(-1) ethanol for 48 h to establish the model of ALD in vitro, and 100, 50, and 25 μmol·L~(-1) concentration of MFA was treated. MiR-378b plasmids(containing the overexpression plasmid-miR-378b mimics, silence plasmid-miR-378b inhibitor, and their respective negative control-miR-378b NCs) were transfected into L02 cells by electroporation to up-regulate or down-regulate the levels of miR-378b in L02 cells. The levels of total cholesterol(TC) and triglyceride(TG) in cells were detected by commercial diagnostic kits and automatic biochemical analyzers. The expression levels of miR-378b in L02 cells were detected by real-time quantitative polymerase chain reaction(qRT-PCR). CaMKK2 mRNA levels were detected by PCR, and protein expressions of related factors involved in lipid synthesis, decomposition, and transport in lipid metabolism were detected by Western blot. The results displayed that ethanol significantly increased TG and TC levels in L02 cells, while MFA decreased TG and TC levels. Ethanol up-regulated the miR-378b level, while MFA effectively inhibited the miR-378b level. The overexpression of miR-378b led to lipid accumulation in ethanol-induced L02 cells, while the silence of miR-378b improved the lipid deposition induced by ethanol. MFA activated the CaMKK2-AMPK signaling pathway by lowering miR-378b, thus improving lipid synthesis, decomposition, and transport, which improved lipid deposition in L02 cells. This study shows that MFA improves lipid deposition in L02 cells by regulating the CaMKK2-AMPK pathway through miR-378b.
Subject(s)
Humans , Ethanol/toxicity , AMP-Activated Protein Kinases/metabolism , Fatty Liver , Triglycerides , MicroRNAs/genetics , Calcium-Calmodulin-Dependent Protein Kinase Kinase/geneticsABSTRACT
Objective::To assess the efficacy of Wenyang Huashi prescription on rehabilitation of patients after allergic fungal rhinosinusitis (AFRS) operation, and its effect on inflammatory factors and immune function. Method::One hundred and forty-four patients were randomly divided into control group and observation group by random number table, with 72 cases in each group. Patients in control group was treated with Messerklinger to remove lesions completely, and got anti-infective therapy for three days, prednisone acetate tablets, 10 mg/time, 2 times/days, fluticasone propionate inhaled aerosol for a continued 4 weeks, 2 sprays/time, 1 time/day, itraconazole capsules at the first, fifth and ninth week after treatment (one course of treatment was 7 days), 0.2 g/time, 1 time/day. In addition to the therapy of meloxicam tablets, patients in observation group were also given local rinsing and oral administration of Wenyang Huashi prescription. The courses of treatment of both groups were 12 weeks. Before the operation and at the fourth and 12th week after the operation, subjective conditions were assessed. And before the operation and at the 12th, 24th and 48th week after the operation, Lund-Kennedy detected by endoscopic sinus surgery and nasal and paranasal sinus outcomes test-20 (SNOT-20) were scored. And the relapse was recorded during 48 weeks after the operation. And levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-1bet (IL-1bet), nuclear factor kappa B (NF-kappa B), intercellular adhesion molecule in peripheral blood-1 (ICAM-1), T lymphocyte subsets (CD3+, CD4+, CD8+ and CD4+ /CD8+) were detected. Result::By rank sum test, the clinical efficacy in observation group was better than that in control group (Z=2.016, P<0.05). At the fourth and 12th week after the operation, scores of nasal obstruction, dizziness, runny nose and dysosmia in observation group were lower than those in control group (P<0.01). And scores of lund-kennedy and SNOT-20 were lower than those in control group (P<0.01). And levels of TNF-α, IL-1β, NF-κB and ICAM-1 were lower than those in control group (P<0.01). After treatment, levels of CD3+, CD4+ /CD8+ and CD4+ were higher than those in control group, and level of CD8+ was lower than that in control group (P<0.05). During the one-year follow-up, the relapse rate in observation group was 7.81%(5/64), which was lower than 22.58%(14/62) in control group (χ2=5.363, P<0.05). Conclusion::Wenyang Huashi prescription can improve short-term and long-term symptoms, improve the comprehensive curative effect, the quality of life and the immune function of the body, alleviate inflammatory injury, reduce the recurrence rate and improve the prognosis, and so is worth further study and use.
ABSTRACT
OBJECTIVE: To observe the clinical efficacy of motherwort injection in the treatment of abnormal uterine bleeding-ovulatory dysfunction(AUB-O),and provide data support for broadening the clinical application range of motherwort injection.METHODS: A multicenter,randomized,prospective study was used.The patients who were diagnosed with AUB-O in Hospital of Chengdu University of Traditional Chinese Medicine in 2018 were randomly divided into the control group and the experimental group according to random numbers.There were 75 cases in the experimental group,7 cases were lost,and 68 cases were the final cases;another 75 cases were in the control group,4 cases were lost,and there were 71 cases in the end.In the control group,only the tranexamic acid was given.On the basis of this,the experimental group was given intramuscular injection of motherwort injection 2 mL/time,b.i.d.,for 3 consecutive days.The clinical TCM symptom scores,blood loss,blood routine,coagulation function,endometrial thickness and effective rate were compared between the two groups.All data were statistically analyzed using IBM SPSS 21.0.RESULTS: After treatment,the total effective rate of the experimental group was 97.06%,which was significantly better than that(84.51%)of the control group(P0.05),but on the 2nd day and the 3rd day after treatment,the difference was statistically different(P<0.05),and the cumulative amount of bleeding after 3 days of treatment was statistically different(P<0.05).The endometrial thickness of the experimental group was lower than that of the control group(P<0.01).CONCLUSION: Motherwort injection combined with basic therapy is effective in the treatment of AUB-O.