Puerarin inhibits HDAC1-induced oxidative stress disorder by activating JNK pathway and alleviates acrolein-induced atherosclerosis.

OBJECTIVE: Atherosclerosis (AS) is a common pathogenesis of cardiovascular diseases. Puerarin (Pue) is a Chinese herbal remedy used to prevent and treat AS. Here, this research investigated the effect of Pue on AS progression. METHODS: ApoE-/- mice were induced with acrolein. Body weight, blood lipid index, inflammatory factors, mitochondrial oxidative stress, and lipid deposition were detected. IL-6 and TNF-α were detected by ELISA. Oil red staining and H&E staining were used to observe the aortic sinus plaque lesions. Serum expressions of inflammatory factors IL-6, TNF-a, SOD, GSH and MDA were detected by ELISA, the mRNA expression levels of HDAC1 in the aorta were detected by RT-qPCR, and IL-6 and TNF-α in the aorta were detected by immunohistochemistry. JNK, p-JNK, OPA-1, and HDAC1 were detected by Western blotting. RESULTS: Pue administration can effectively reduce lipid accumulation in AS mice induced by acrolein. Pue promoted the activity of SOD, GSH and MDA, and inhibited the formation of atherosclerotic plaques and the process of aortic histological changes. Pue reduced IL-6 and TNF-α. HDAC1 expression was down-regulated and p-JNK-1 and JNK protein expression was up-regulated. CONCLUSION: Pue reduces inflammation and alleviates AS induced by acrolein by mediating the JNK pathway to inhibit HDAC1-mediated oxidative stress disorder.

Puerarin alleviates acrolein-induced atherosclerosis by activating the MYH9-mediated SIRT1/Nrf2 cascade to inhibit the activation of inflammasome.

Puerarin (Pue) has significant antioxidant and anti-inflammatory properties. This work was designed to clarify and investigate the potential mechanisms of Pue in atherosclerosis (AS) progression. In vivo, acrolein (Acr) was inhaled through drinking water to construct AS model. In vitro, CCK-8 assay and lactate dehydrogenase (LDH) assay kit were used to detect cell viability. Apoptosis was detected by flow cytometry. The content of malondialdehyde (MDA) was determined by commercial kit, the level of inflammatory factors was detected by ELISA, and proteins were determined by western blot. Pue administration could effectively reduce blood lipid level in Acr-fed mice. Pue suppressed oxidative stress, the formation of atherosclerotic plaques, and the process of aortic histological changes. Pue pretreatment decreased MDA in HUVECs and maintained the activity of antioxidant enzymes. Pue upregulated SIRT1/Nrf2 cascade in HUVECs. Pue increased MYH9 and inhibited NLRP3 inflammasome-related proteins, and the inhibition of MYH9 significantly impaired Pue-induced Nrf2 activation. Moreover, HUVEC cytotoxicity and apoptosis are alleviated by Pue, in addition to NLRP3-mediated pyroptosis in HUVECs induced by Acr. MYH9 inhibitors effectively suppressed the pyroptosis induced by Acr and prevented injury to HUVECs. In addition, Pue promoted SIRT1/Nrf2 cascade activation in HUVECs. Pue may alleviate Acr-induced AS by activating the MYH9-mediated SIRT1/Nrf2 cascade to inhibit inflammasome activation.

The value of diffusion kurtosis imaging and intravoxel incoherent motion quantitative parameters in predicting synchronous distant metastasis of rectal cancer.

BACKGROUND: The incidence and mortality rate of rectal cancer are still high, the metastasis of rectal cancer are main causes of death. The control of the distant metastasis is one of the main concerns in the treatment of locally advanced rectal cancer, but there are few studies on predicting synchronous distant metastasis (SDM) of rectal cancer. METHOD: The data of patients with rectal adenocarcinoma confirmed by endoscopic biopsy or postoperative pathology from September 2015 to May 2020 in hospital A (center 1) and hospital B (center 2) were analyzed retrospectively, including age, sex, carcinoembryonic antigen, carbohydrate antigen 19-9, tumor location, tumor length, image staging and characteristics. The average age of the 169 patients consisting of 105 males and 64 females in study is 61.2 years. All patients underwent rectal routine rectal MRI, DKI and IVIM examinations on a 3.0-T scanner. Two radiologists sketched regions of interest (ROIs) on b = 1000 s/mm2 DKI and IVIM images to obtain quantitative parameters with FireVoxel manually. We evaluated the difference of histogram analysis, clinical and image data between SDM group and non-SDM group, and evaluated the efficacy of each index in predicting SDM of rectal cancer. RESULTS: The 90th percentile of f values in the SDM group is lower than that in the non-SDM group (29.4 ± 8.4% vs. 35 ± 17.8%, P = 0.005). CA19-9 in the SDM group is higher than that in the non-SDM group (P = 0.003). Low and high rectal cancer are more likely to develop SDM than middle rectal cancer (P = 0.05 and P = 0.047). The combination of these three indexes has a greater area under the curve (AUC) than any one index (0.801 vs. 0.685 (f (90th percentile)) and 0.627 (CA19-9), P = 0.0075 and 0.0058, respectively), and its specificity and sensitivity are 80.0% and 71.6%, respectively. When this combination is incorporated into the predictive nomogram model, the c-index is 0.801 (95% confidence interval (CI): 0.730-0.871). CONCLUSIONS: IVIM quantitative parameters combine with CA19-9 and tumor location can better predict the risk of SDM of rectal cancer.

Features of CT and EUS in mesenteric plexiform neurofibroma with Neurofibromatosis type I: A case report.

Plexiform neurofibroma(PNF) is a rare benign tumor of the peripheral nerve, belonging to a subtype of neurofibroma. PNF is common in the head, neck and trunk. It is uncommonly observed in the mesentery. We report a case of mesenteric PNF in a 64-year-old man history of neurofibromatosis type I(NF1), which caused abdomen pain. In addition, the computer tomography(CT) and endoscopic ultrasonography(EUS) manifestations of mesenteric PNF were analyzed. The imaging appearance of a mesenteric plexiform neurofibroma is that many low-density (CT) /mixed echo (EUS) soft tissue masses surrounding the superior mesenteric artery, but not surrounding the superior mesenteric vein. Our case adds to the limited literature regarding NF1 presenting with mesenteric PNF. The computer tomography and endoscopic ultrasonography may facilitate confirma diagnosis of mesenteric PNF.

Ginsenoside Rg3 suppresses the formation of vasculogenic mimicry of gastric cancer SGC7901 cells by inhibiting Wnt/β-catenin pathway in vitro / 中国肿瘤生物治疗杂志

@#Objective: To investigate the effects of ginsenoside Rg3 on the formation of vasculogenic mimicry (VM) in gastric cancer cell line SGC7901 and its molecular mechanism. Methods: MTT assay was used to detect the effect of different concentrations of Rg3 on the proliferation of SGC7901 cells. SGC7901 cells were grouped as follows: BML-284 group, XAV-939 group, Rg3 group, Rg3+ BML-284 group and blank group. Transwell chamber assay was used to detect cell invasion and migration; the formation of VM was observed by tube formation assay; the secretion of MMP-9 and MMP2 was detected by ELISA; the mRNA expressions of GSK-3β and Wnt2B were detected by qPCR; the expression of β-Catenin protein in cells was analyzed by WB; and nuclear entry of β-Catenin was examined by Immunofluorescence. Results: Ginsenoside Rg3 inhibited the proliferation of SGC7901 cells in a time- and concentrationdependent manner; compared with the blank group, 40 mg/L Rg3 significantly inhibited the invasion and migration of SGC7901 cells (both P<0.05) and VM formation (P<0.05); in the meanwhile, the expressions of intracellular GSK-3β, Wnt2B mRNA and β-catenin protein, as well as the nuclear entry of β-catenin were significantly inhibited (all P<0.05). The invasion, migration and VM formation of SGC7901 cells in Rg3+BML-284 group were not significantly different from those in the blank group (all P>0.05). Conclusion: Rg3 can inhibit cell invasion, migration and VM formation in SGC7901 cells by inhibiting the activation of Wnt/β-Catenin pathway.

Hyperglycemia and Advanced Glycation End Products Regulate miR-126 Expression in Endothelial Progenitor Cells.

BACKGROUND/AIMS: Dysfunction of endothelial progenitor cell (EPCs) contributes to diabetic vascular disease. We reported that downregulated miR-126 in diabetic patients causes EPC dysfunction. The study was designed to investigate how high glucose (HG) and advanced glycation end products (AGEs) regulate miR-126 expression and whether miR-126 mediates the effects of HG and AGEs on EPCs. METHODS: We first tested the effects of glucose (5.5-50 mM) and AGEs at 50-200 mg/l on EPC proliferation and selected HG at 50 mM and AGEs at 50 mg/l for further experiments. EPCs were stimulated with HG and AGEs, and miR-126 expression was measured by real-time PCR. Reactive oxygen species (ROS) were measured by immunofluorescence microscopy and flow cytometry. IL-6 and TNF-α levels in EPC supernatants were determined by ELISA. The effects of miR-126 on ROS and inflammatory markers under stimulation of HG and AGEs were also assessed. Finally, the effects of inhibitors of PI3K and Akt on AGE-mediated miR-126 expression were examined. RESULTS: HG and AGEs increased IL-6, TNF-α and ROS and decreased miR-126 expression in EPCs. miR-126 negatively regulated IL-6, TNF-α and ROS. miR-126 overexpression reduced and miR-126 inhibition further increased the inflammatory markers and ROS induced by HG and AGEs. Inhibitors of PI3K and Akt further decreased miR-126 expression in the presence of AGEs. CONCLUSIONS: In conclusion, hyperglycemia and AGEs decrease miR-126 expression in EPCs. Recovering miR-126 expression may protect EPCs against dysfunction induced by HG and AGEs.

MicroRNA-130a regulates autophagy of endothelial progenitor cells through Runx3.

Dysfunction of endothelial progenitor cells (EPC) contribute to diabetic vascular disease. MicroRNAs (miRNAs) are key regulators of diverse cellular processes, including angiogenesis. We recently reported that downregulated miR-130a in patients with Type 2 diabetes mellitus (DM) results in EPC dysfunction, including increased apoptosis, likely via its target runt-related transcription factor 3 (Runx3). However, whether miR-130a affects the autophagy of EPC is unknown. The aim of the present study was to explore the effects of miR-130a on the autophagy and cell death of EPC, as well as their expression of Beclin 1 (BECN1; an initiator of autophagosome formation) and the anti-apoptotic protein Bcl2 (which binds to and inactivates BECN1), and the role of Runx3 in mediating these effects. The EPC were cultured from peripheral blood mononuclear cells of diabetic patients and non-diabetic controls. Cells were transfected with an miR-130a inhibitor, or mimic-miR-130a or mimic-miR-130a plus lentiviral vector expressing Runx3 to manipulate miR-130a and/or Runx3 levels. The number of autophagosomes was counted under transmission electron microscopy and cell death was examined by flow cytometry. The mRNA expression of Beclin1 was measured by real-time polymerase chain reaction and the protein expression of Beclin1 and Bcl2 was determined by western blotting. Both the number of autophagosomes and Beclin1 expression were increased in EPC from patients with DM. Inhibition of miR-130a increased the number of autophagosomes and Beclin1 expression, but attenuated Bcl2 expression. Overexpression of miR-130a decreased the number of autophagosomes, cell death and Beclin1 expression, but promoted Bcl2 expression; these effects were mediated by Runx3. In conclusion, miR-130a is important for maintaining normal autophagy levels and promoting the survival of EPC via regulation of Bcl-2 and Beclin1 expression, via Runx3. MiR-130a may be a regulator linking apoptosis and the autophagy of EPC.