Urinary sediment CCL5 messenger RNA as a potential prognostic biomarker of diabetic nephropathy.

BACKGROUND: Urinary sediment messenger RNAs (mRNAs) have been shown as novel biomarkers of kidney disease. We aimed to identify targeted urinary mRNAs in diabetic nephropathy (DN) based on bioinformatics analysis and clinical validation. METHODS: Microarray studies of DN were searched in the GEO database and Nephroseq platform. Gene modules negatively correlated with estimated glomerular filtration rate (eGFR) were identified by informatics methods. Hub genes were screened within the selected modules. In validation cohorts, a quantitative polymerase chain reaction assay was used to compare the expression levels of candidate mRNAs. Patients with renal biopsy-confirmed DN were then followed up for a median time of 21 months. End-stage renal disease (ESRD) was defined as the primary endpoint. Multivariate Cox proportional hazards regression was developed to evaluate the prognostic values of candidate mRNAs. RESULTS: Bioinformatics analysis revealed four chemokines (CCL5, CXCL1, CXLC6 and CXCL12) as candidate mRNAs negatively correlated with eGFR, of which CCL5 and CXCL1 mRNA levels were upregulated in the urinary sediment of patients with DN. In addition, urinary sediment mRNA of CXCL1 was negatively correlated with eGFR (r = -0.2275, P = 0.0301) and CCL5 level was negatively correlated with eGFR (r = -0.4388, P < 0.0001) and positively correlated with urinary albumin:creatinine ratio (r = 0.2693, P = 0.0098); also, CCL5 and CXCL1 were upregulated in patients with severe renal interstitial fibrosis. Urinary sediment CCL5 mRNA was an independent predictor of ESRD [hazard ratio 1.350 (95% confidence interval 1.045-1.745)]. CONCLUSIONS: Urinary sediment CCL5 and CXCL1 mRNAs were upregulated in DN patients and associated with a decline in renal function and degree of renal interstitial fibrosis. Urinary sediment CCL5 mRNA could be used as a potential prognostic biomarker of DN.

Two resveratrol analogs, pinosylvin and 4,4'-dihydroxystilbene, improve oligoasthenospermia in a mouse model by attenuating oxidative stress via the Nrf2-ARE pathway.

Two synthesized resveratrol analogs from our laboratory, namely pinosylvin (3,5-dihydroxy-trans-stilbene, PIN) and 4,4'-dihydroxystilbene (DHS), have been carefully evaluated for treatment of oligoasthenospermia. Recent studies have demonstrated that PIN and DHS improved sperm quality in the mouse. However, the mechanism of action of PIN and DHS on oligoasthenospermia remains unknown. Herein, we investigated the mechanistic basis for improvements in sperm parameters by PIN and DHS in a mouse model of oligoasthenospermia induced by treatment with busulfan (BUS) at 6 mg/kg b.w.. Two weeks following busulfan treatment, mice were administered different concentrations of PIN or DHS daily for 2 consecutive weeks. Thereafter, epididymal sperm concentration and motility were determined, and histopathology of the testes was performed. Serum hormone levels including testosterone (T), luteinizing hormone (LH), and follicle stimulating hormone (FSH) were measured using corresponding specific enzyme-linked immunosorbent assay (ELISA) kits. Testicular mRNA expression profiles were determined by RNA sequencing analysis. These findings were validated by quantitative real-time PCR, western blotting and ELISA. Both PIN and DHS improved the epididymal sperm concentration and motility, enhanced testosterone levels, and promoted testicular morphological recovery following BUS treatment. PIN treatment was found to significantly reduce oxidative stress via the nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE)-dependent antioxidant, glutathione peroxidase 3. DHS treatment significantly reduced oxidative stress via the Nrf2-ARE-dependent antioxidants glutathione S-transferase theta 2 and glutathione S-transferase omega 2. In summary, PIN and DHS ameliorated oligoasthenospermia in this mouse model by attenuating oxidative stress via the Nrf2-ARE pathway.

Ni-Al Bimetallic Catalyzed Enantioselective Cycloaddition of Cyclopropyl Carboxamide with Alkyne.

A Ni-Al bimetallic catalyzed enantioselective cycloaddition reaction of cyclopropyl carboxamides with alkynes has been developed. A series of cyclopentenyl carboxamides were obtained in up to 99% yield and 94% ee. The bifunctional-ligand-enabled bimetallic catalysis proved to be an efficient strategy for the C-C bond cleavage of unreactive cyclopropanes.

Ligand-Accelerated Direct C-H Arylation of BINOL: A Rapid One-Step Synthesis of Racemic 3,3'-Diaryl BINOLs.

An ortho-selective rhodium-catalyzed direct C-H arylation of 1,1'-bi-2-naphthol (BINOL), to deliver the widely used but not easily available 3,3'-diaryl BINOL, has been developed. This highly efficient one-step synthetic approach is the shortest route to date and is greatly facilitated by the newly developed ligand system comprising tBu2 PCl, Ph2 -cod, and Cy3 P⋅HBF4 . In addition, the same procedure can facilitate the challenging syntheses of 3-bulkyaryl BINOLs in good to excellent yields.

Early and midterm results of thoracic endovascular aortic repair of chronic type B aortic dissection.

OBJECTIVE: The optimal treatment for chronic type B dissection remains controversial. This study reports early and midterm results of thoracic endovascular aortic repair for chronic type B aortic dissection. METHODS: From June 2001 to September 2007, a total of 84 patients with chronic type B aortic dissection underwent thoracic endovascular aortic repair. The time between onset of dissection and thoracic endovascular aortic repair was 13.9 +/- 22.0 months (range, 1-120 months). All patients were followed up from 6 to 86 months (mean, 33.2 +/- 19.2 months). RESULTS: The entry tear was completely sealed in 77 cases (91.7%) during thoracic endovascular aortic repair. The incidence of incomplete seal was 8.3%. The 1-month mortality was 1.2%. One patient had retrograde type A dissection 1 month after the operation. Four patients underwent a second thoracic endovascular aortic repair during follow-up, for endoleak in 3 patients and for newly formed intimal tear in 1 patient. Seven patients (8.3%) died during follow-up. Three died of rupture of the thoracic aorta because of endoleak. The Kaplan-Meier actuarial survival curve showed a 5-year survival of 84.4%. At 5 years, 75.2% of patients were alive with neither endoleak nor reintervention. CONCLUSIONS: Early and midterm results show that thoracic endovascular aortic repair was effective in the treatment of chronic type B aortic dissection. Endoleak was the main cause of death during follow-up. With increased surgical experience and refinement of the stent graft, results are likely to improve in the future.

A study of aortic dimension in type B aortic dissection.

Difference between arch diameter and true lumen diameter in the descending aorta was studied in patients with type B aortic dissection. The diameters of the aortic arch (Proximal ) and mid-descending aorta (Distal ) were measured on computer tomography angiography (CTA) in 20 healthy adults. Forty-two patients with type B aortic dissection who underwent endovascular repair were divided into two groups: an acute group (23 patients) and a chronic group (19 patients). The diameters of the arch (Proximal ) and the true lumen of the mid-descending aorta (Distal ) were measured on digital subtraction angiography (DSA) and CTA. The taper ratio was defined as (Proximal -Distal )/(Proximal )x100%. In the control group, the taper ratio was 13.0+/-4.7% on CTA. In the acute patients group, the taper ratio was 23.6+/-11.3% on DSA and 21.9+/-12.1% on CTA. In the chronic patients group, the taper ratio was 31.5+/-13.6% on DSA and 30.1+/-11.4% on CTA. In both acute and chronic type B aortic dissection, the aorta tapers significantly from arch to true lumen in the descending aorta. Stent-graft with tapered design may be a viable treatment option for endovascular repair of type B aortic dissection.

Endovascular repair of acute type B aortic dissection: early and mid-term results.

OBJECTIVE: To evaluate early and mid-term results of endovascular repair of acute type B aortic dissection by stent graft. METHODS: From June 2001 to May 2005, 63 patients with acute type B aortic dissection underwent stent graft implantation. The study included 59 men and 4 women with an average age of 50.4 +/- 11.4 years (range, 31-80 years). Four patients underwent stent-graft implantation in the acute phase. Fifty-nine patients with acute type B dissection underwent stent-graft implantation 2 weeks after the onset of dissection. All patients were followed up from 1 to 47 months (average, 11.7 +/- 10.6 months). The clinical data of the patients were analyzed. RESULTS: The primary tear was incompletely sealed in three cases. The incidence of incomplete seal was 4.8%. Ascending aortic dissection occurred in three cases. One occurred during operation. The other two occurred at 1 day and 10 months after stent-graft implantation. Two patients died within 30 days after operation. One died of rupture of the ascending aortic dissection. The other one died of acute renal failure. The 1-month mortality was 3.2%. Four patients underwent a second stent-graft implantation before discharge. One year after stent-graft implantation, complete thrombosis of the false lumen in the thoracic aorta was achieved in 98.4% of patients, and the maximum diameter of the descending aorta decreased 11.2% +/- 7.3%. Three patients died within the follow-up time. Mortality during the follow-up period was 4.8%. One patient died of peptic ulcer hemorrhage. Another one died of rupture of the ascending aortic dissection. The third one died of unknown reasons. The actuarial survival curve by the Kaplan-Meier method showed a 4-year survival rate of 89.4%. CONCLUSIONS: Early and mid-term results showed that endovascular repair was effective in treatment of acute type B aortic dissection. With the enrichment of doctors' experience and refinement of the device, better results are expected in the future.

Treating aortic dissection and penetrating aortic ulcer with stent graft: thirty cases.

BACKGROUND: The purpose of this study is to evaluate the feasibility and safety of stent graft in the treatment of aortic dissection and penetrating aortic ulcer. METHODS: From June 2001 to April 2004, 25 patients with aortic dissection and 5 patients with penetrating aortic ulcer received stent-graft implantation. Within this group were 24 male and 6 female patients, with an average age of 52.3 +/- 11.9 years. One patient was diagnosed as type A dissection, 23 patients as chronic type B dissection, 1 patient as acute type B dissection, and the remaining 5 patients with penetrating aortic ulcer. Among the 25 patients with aortic dissection, 3 had contained rupture. All patients were followed up in 1 to 32 months. RESULTS: All patients received stent-graft implantation. There were 5 type I endoleaks. Retrograde ascending aortic dissection occurred during the operation in 1 patient. Two other retrograde ascending aortic dissections occurred in 2 patients 1 day and 7 days, respectively, after stent-graft implantation. Two patients died 1 day and 18 days, respectively, after operation because of rupture of ascending aortic dissection. One-month mortality rate was 6.7%. No death occurred during follow-up time. One patient received a second stent-graft implantation 20 months after the first procedure. CONCLUSIONS: Serious complications may develop after stent-graft implantation, but the early results of treatment of aortic dissection and penetrating aortic ulcer with stent graft were satisfactory. Long-term follow-up was needed.