Protection of CAPE-pNO2 Against Chronic Myocardial Ischemia by the TGF-Β1/Galectin-3 Pathway In Vivo and In Vitro.

Although it is known that caffeic acid phenethyl ester (CAPE) and its derivatives could ameliorate acute myocardial injury, their effects on chronic myocardial ischemia (CMI) were not reported. This study aimed to investigate the potential effect of caffeic acid p-nitro phenethyl ester (CAPE-pNO2, a derivative of CAPE) on CMI and underlying mechanisms. SD rats were subjected to high-fat-cholesterol-diet (HFCD) and vitamin D3, and the H9c2 cells were treated with LPS to establish CMI model, followed by the respective treatment with saline, CAPE, or CAPE-pNO2. In vivo, CAPE-pNO2 could reduce serum lipid levels and improve impaired cardiac function and morphological changes. Data of related assays indicated that CAPE-pNO2 downregulated the expression of transforming growth factor-ß1 (TGF-ß1) and galectin-3 (Gal-3). Besides, CAPE-pNO2 decreased collagen deposition, the number of apoptotic cardiomyocytes, and some related downstream proteins of Gal-3 in the CMI rats. Interestingly, the effects of CAPE-pNO2 on TGF-ß1, Gal-3, and other proteins expressed in the lung were consistent with that in the heart. In vitro, CAPE-pNO2 could attenuate the fibrosis, apoptosis, and inflammation by activating TGF-ß1/Gal-3 pathway in LPS-induced H9c2 cell. However, CAPE-pNO2-mediated cardioprotection can be eliminated when treated with modified citrus pectin (MCP, an inhibitor of Gal-3). And in comparison, CAPE-pNO2 presented stronger effects than CAPE. This study indicates that CAPE-pNO2 may ameliorate CMI by suppressing fibrosis, inflammation, and apoptosis via the TGF-ß1/Gal-3 pathway in vivo and in vitro.

CAPE-pNO2 ameliorates diabetic brain injury through modulating Alzheimer's disease key proteins, oxidation, inflammation and autophagy via a Nrf2-dependent pathway.

AIMS: CAPE-pNO2, an active derivative of caffeic acid phenethyl ester, has been verified to exert protection of diabetic cardiomyopathy and diabetic nephropathy. The present study aims to explore the brain protection effects and potential mechanisms of CAPE-pNO2 on streptozotocin-induced diabetic brain injury in vivo and in vitro. MAIN METHODS: Biochemical indexes including triglyceride, total cholesterol, superoxide dismutase and malondialdehyde contents were detected. The histopathological structure of hippocampus and cerebral cortex were determined. Immunofluorescence and immunoblot methods were used to assess expression of oxidative stress, inflammation and autophagy pathway-related proteins of diabetic brain in vivo. Alzheimer's disease (AD)-associated key proteins were also checked in vivo. DCFH-DA assay, immunofluorescence and immunoblot methods were applied to verify the master role of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) in vitro. KEY FINDINGS: First, CAPE-pNO2 could rescue the diabetic brain atrophy and diminish CA1 and CA3 cells of hippocampus and cerebral cortex. Second, CAPE-pNO2 could decrease Aß and p-tau (S396) expression through anti-oxidation, anti-inflammation and autophagy induction in vivo. Last, CAPE-pNO2 could down-regulate p-tau (S396) expression through Nrf2-related anti-oxidation mechanisms in vitro. SIGNIFICANCE: CAPE-pNO2 may exert brain protection via Nrf2-dependent way in diabetes. Additionally, Nrf2 was capable of regulating p-tau (S396) expression that is critical to AD.

[Objective optical quality after orthokeratology].

OBJECTIVE: To determine the changes of objective optical quality after orthokeratology. METHODS: Prospective, self-controlled study. Optical quality, including objective scatter index (OSI), modulation transfer function (MTF) cutoff frequency, contrast visual acuity (CVA) and objective tear film quality, was assessed with the OQAS II instrument before and 1 week, 1 month, and 3 months after orthokeratology. Parameters of corneal astigmatism and e value from topography were also assessed. The data was analyzed using one-way ANOVA. RESULTS: Cylinder refraction was (-0.39 ± 0.39)D, (-0.65 ± 0.57)D, (-0.79 ± 0.56)D, and (-0.81 ± 0.53) D, respectively, at the four timepoints, and there was a statistically significant difference between before and after therapy (P < 0.05). Uncorrected visual acuity was 3.97 ± 0.51, 4.95 ± 0.12, 5.00 ± 0.06, and 5.00 ± 0.05, respectively. The e value was 0.37 ± 0.24, -0.23 ± 0.42, -0.29 ± 0.39, and -0.30 ± 0.37, respectively. The negative values after therapy were significantly different from the value before therapy (P < 0.01). The corneal astigmatism in 3 mm diameter was (1.27 ± 0.75) D, (1.06 ± 0.69) D, (1.11 ± 0.68) D , and (1.15 ± 0.67) D, respectively. There was no significant difference in astigmatism between before and after therapy (P ≥ 0.05). After therapy, the OSI increased from 0.59 ± 0.47 before therapy to 0.99 ± 0.66 at 1 week, 1.47 ± 1.17 at 1 month, and 1.49 ± 1.03 at 3 months. The difference between pre- and post-therapy OSI values was statistically significant (P < 0.05). The MTF cutoff frequency decreased from (36.6 ± 12.0) cpd before therapy to (34.2 ± 8.9) cpd at 1 week, (27.9 ± 12.6) cpd at 1 month, and (27.7 ± 11.6) cpd at 3 months after therapy. The difference in MTF cutoff frequency between before and 1 month after therapy was statistically significant (P < 0.05). The 100% CVA, 20% CVA, and 9% CVA all declined after therapy, but there was no statistically significant difference between before and after therapy. The OSI of tear film quality was 1.27 ± 1.12, 2.09 ± 1.67, 2.07 ± 1.12, and 2.10 ± 1.33, respectively, and the difference was statistically significant between before and after therapy (P < 0.05). CONCLUSIONS: After 3 months of orthokeratology, the corneal central astigmatism remained, and the e value became negative, while OSI increased, and MTF cutoff frequency and tear film quality declined. The alteration was more and more obvious along with the therapy within 1 month, and was not significant within the following month. After short-term corneal reshaping, the ocular optical quality declined in some degree, but the loss was acceptable.

[Preliminary study on differential expression of plasma proteins of patients with Takayasu's arteritis in different stage].

OBJECTIVES: To investigate differential expression of plasma proteins of patients with Takayasu's arteritis to screen disease-related or phase-related proteins or biomarkers. METHODS: From March, 2005 to January, 2006, Plasma of 20 patients with acute Takayasu's arteritis, 20 patients with chronic Takayasu's arteritis, and 20 healthy people as control were collected. Plasma proteins were profiled by two-dimensional electrophoresis. Spots of differential expression were screened by computerized map analysis and identified by matrix assisted laser desorption/ionization time of flight-mass spectrometry. Circulation levels of parts of differential expression proteins were investigated by Elisa in each subject. RESULTS: Fourteen differential expression proteins were identified, including serum amyloid A, serum amyloid P, fibrinogen, complement C3c, C7, C4 binding protein, factor H related protein-1, immunoglobin, alpha-acid glycoprotein, RAG1 protein, alpha1-microglobin, apolipoprotein A-I, A-IV, transthyretin, haptoglobin. Proteins related to acute and chronic phase were serum amyloid A, fibrinogen, transthyretin, haptoglobin; Circulation levels of Serum amyloid A (SAA) and Complement C4 binding protein (C4BP) were significantly increased in active TA patients comparing to that in inactive TA patients and in controls (SAA: 95.9 vs 49.2, P = 0.009 and 23.9 mg/L, P = 0.001, respectively; C4BP: 88.5 vs 61.7, P = 0.023 and 32.6 mg/L, P < 0.001, respectively). CONCLUSIONS: Acute phase proteins and immune proteins may possible be markers for diagnosis and activity of Takayasu's arteritis, Complement activity, complement modulation protein and antibody production may be involved in immune mechanism of Takayasu's arteritis. Further study of these proteins may be helpful to elucidate the pathologic mechanism of Takayasu's arteritis.

[Experiences of retroperitoneal approach for aortoiliac reconstruction].

OBJECTIVE: To summarize experiences of aortoiliac reconstruction through retroperitoneal approach. METHODS: Twenty-eight patients underwent retroperitoneal aortoiliac reconstructions, including aortic aneurysmectomy with graft replacement, aortic endarterectomy with patch angioplasty, thoraco-abdominal aortic bypass, resection of retroperitoneal mass with ilio-femoral bypass, iliac aneurysmectomy with aorto-external iliac artery bypass, removal of aortoiliac foreign body, common iliac endarterectomy, aorto (ilio)-femeral bypass and common ilio-femo-popliteal bypass. Drainage tubes were placed retroperitoneally in 24 cases. RESULTS: All operations in this group were successful without perioperative death. The volume of intra-operative bleeding was 100-400 ml (mean 240 ml). Blood transfusion were employed in 2 cases. Retroperitoneal drainage was 50-170 ml (mean 85 ml). Naso-gastric tubes were removed 28 h on average after operation. All patients recovered uneventfully except that cardiac insufficiency, stress ulcer and retroperitoneal hematoma were present in 3 patients respectively. Twenty-two patients were followed up from 3 months to 2.5 years. One patient died of AMI 2 years after operation. One patient receiving ilio-femo-popliteal bypass was found to have occlusion of femo-popliteal segment of prosthetic graft. One patient developed brain hemorrhage 1.5 years postoperatively. All the other followed-up patients were living well. CONCLUSION: Retroperitoneal approach, not violating the peritoneal cavity, offers certain physiological advantages associated with minimal disturbance of gastrointestinal and respiratory function, thereby decreasing respiratory complications and postoperative ileus, avoiding intra-abdominal adhesions with their attendant risk of early and late small bowel obstruction. It proved to be a simple and safe alternative for surgical treatment of aortoiliac diseases.