ABSTRACT
Diabetic nephropathy constitutes the leading cause for end-stage kidney disease. Ginkgetin is a common natural non-toxic biflavone and fulfills pleiotropic pharmacological characterizations, such as anti-inflammation and kidney injury. Nevertheless, its efficacy in diabetic nephropathy remains elusive. Here, ginkgetin exhibited little cytotoxicity in glomerular mesangial cells. Of note, ginkgetin restrained high glucose (HG)-induced mesangial cell proliferation and oxidative stress by inhibiting ROS and malonaldehyde levels, but enhancing antioxidant SOD activity. Additionally, ginkgetin suppressed HG-evoked transcript and release of inflammatory cytokine TNF-α, IL-1ß, and IL-6. Concomitantly, the increased extracellular matrix (ECM) deposition in HG-treated glomerular mesangial cells was attenuated by ginkgetin via decreasing expression of collagen IV, fibronectin, and laminin. Intriguingly, ginkgetin-restored HG-impaired autophagy; whereas blocking autophagy by its inhibitor 3-MA overturned ginkgetin function against HG-evoked mesangial cell dysfunction. Mechanistically, ginkgetin-mediated AMPK/mTOR axis accounted for HG-impaired autophagy. Importantly, blockage of AMPK signaling reversed ginkgetin-restored autophagy and its protective efficacy against HG-induced dysfunction in mesangial cells. Thus, these findings highlight that ginkgetin may attenuate HG-evoked mesangial cell hyperplasia, oxidative stress, inflammation, and ECM accumulation by activating AMPk/mTOR-mediated autophagy pathway. Therefore, ginkgetin may alleviate the progression of diabetic nephropathy by regulating glomerular mesangial cell dysfunction, supporting a promising therapeutic agent against diabetic nephropathy.
Subject(s)
Anti-Inflammatory Agents/pharmacology , Antioxidants/pharmacology , Autophagy/drug effects , Biflavonoids/pharmacology , Diabetic Nephropathies/drug therapy , Glucose/metabolism , Oxidative Stress/drug effects , AMP-Activated Protein Kinases/metabolism , Collagen/metabolism , Extracellular Matrix/drug effects , Fibronectins/metabolism , Humans , Inflammation/drug therapy , Malondialdehyde/metabolism , Mesangial Cells , Signal Transduction , Superoxide Dismutase/metabolism , TOR Serine-Threonine Kinases/metabolismABSTRACT
Objective To evaluate the clinical efficacy of transjugular intrahepatic portosystem shunt (TIPS) and gastric coronary vein embolization (GCVE) in the treatment of patients with cirrhosis,portal hypertension and upper gastrointestinal bleeding.Methods From Jan 2014 to May 2017 72 patients were enrolled and divided into the TIPS group (36 cases,receiving TIPS) and TIPS + E group (36 cases,byTIPS+GCVE).Results Portal vein diameter (1.21 ±0.08)cm vs.(1.26 ±0.09)cm,portal pressure (23.9 ± 2.1) cmH2O vs.(25.1 ± 2.2) cmH2O and congestion index (0.06 ± 0.03) cm/s vs.(0.08 ±0.03) after 1 month of treatment in TIPS + E group was significantly lower than the TIPS group,and the portal vein velocity was significantly higher than that of the TIPS group (42 ± 6) cm/s vs.(38 ± 7) cm/s,t =2.491,2.367,2.828,t =2.343,all P ＜ 0.05.The Child-Pugh score in the TIPS + E group was significantly lower than that in the TIPS group (7.9 ± 1.4) vs.8.6 ± 1.6,t =2.074,P =0.042).There was no statisticall different difference in postoperative hepatic encephalopathy in the two groups (17％ vs.11％,x2 =0.465,P =0.496).The one-year rebleeding rates in the TIPS group and the TIPS + E group were 14％ and 3％,respectively.The risk of rebleeding in the TIPS + E group was significantly lower than that in the TIPS group (HR =0.218,P =0.041).The one-year access obstruction rates in the TIPS group and the TIPS + E group were 17％ and 14％,respectively.(P =0.679).The all-cause mortality rates of the TIPS group and the TIPS + E group were 8％ and 3％,respectively,showing no statistically (P =0.299).Conclusions TIPS + GCVE therapy in the treatment of portal hypertensive upper gastrointestinal bleeding effectively reduces the risk of rebleeding.
ABSTRACT
Objective To assess the correlation between fundic gland polyps and colorectal neoplasia. Methods Clinical records of patients who underwent both gastroduodenoscopy and colonoscopy during the same period were retrospectively analyzed. A total of 195 patients were enrolled into the study,65 diagnosed as having fundic gland polyps and 130 as controls matched with age and sex. Colonoscopic findings were compared between the two groups. Results Colorectal neoplasia was identified in 12 (18. 5%) of 65 patients and in 8 (6. 2%) of 130 controls with significant difference (P =0. 008) . Stratification analysis suggested that the incidence of colorectal neoplasia in fundic gland polyps group was higher in females or aged less than 50 than that of the control group(P=0. 023,0. 008). Conclusion Patients with fundic gland polyps have significantly higher risk for colorectal neoplasia. A screening colonoscopy may be necessary for patients with fundic gland polyps to detect colorectal neoplasia.