Oxidative Three-Component Selenofunctionalization of Alkenes: Convenient Access to Vicinally Functionalized Selenides.

Three-component selenofunctionalization processes of olefins, diselenides and sulfonamides, water, alcohols, or acids utilizing 1-fluoropyridinium triflate (FP-OTf) as a reaction promoter are reported. Under the optimal conditions, a broad range of vicinally functionalized selenide derivatives was accessible with high yields and excellent functional group compatibilities. Mechanistic studies revealed that the FP-OTf played a key role in this selenofunctionalization process.

Photocatalytic Aerobic Cyclization of N-Propargylamides Enabled by Selenium-π-Acid Catalysis.

A dual catalytic approach combining photocatalyst and selenium-π-acid synergy has been used to cyclized of N-propargylamides. This method offers readily access to oxazole aldehydes under chemical oxidant-free conditions with low catalyst loadings, where air acts as a terminal and gratuitous oxidant. The reaction is demonstrated with a range of substrates, including aryl and alkyl propargyl amides, and in the late-stage functionalization of several amide-containing drug molecules. Mechanistic studies suggest that the acridinium catalyst is able to oxidize diselenide and generate singlet oxygen (1 O2 ), which is responsible for this transformation.

N-Fluorobenzenesulfonimide-Mediated Intermolecular Carboselenenylation of Olefins with Aromatics and Diselenides.

Intermolecular carboselenenylation of easily accessible alkenes by utilizing diselenides and N-fluorobenzenesulfonimide (NFSI) under metal-free and mild conditions is reported. Preliminary mechanistic studies indicate that the oxidation of diselenide by NFSI through a single-electron-transfer process produces an active selenenyl cationic radical species that initiates the intermolecular carboselenenylation of olefins, forming key Se-C and C-C bonds. Under optimized conditions, a broad spectrum of functionally and structurally diverse selenoether derivatives with promising yields is accessed with a very high functional group tolerance.

Iodine pentoxide-mediated oxidative selenation and seleno/thiocyanation of electron-rich arenes.

A simple and efficient method for the regioselective selenation of electron-rich arenes by employing non-metal inorganic iodine pentoxide (I2O5) as a reaction promoter under ambient conditions has been developed. The present protocol showed broad functional group tolerance and easy-to-operate and time-economical features. Additionally, this protocol also allows access to 3-seleno and 3-thiocyanoindoles by the use of readily available selenocyanate and thiocyanate salts. A mechanistic study indicated that the transformation operated through selenenyl iodide-induced electrophilic substitution processes.

Geniposide Prevents Hypoxia/Reoxygenation-Induced Apoptosis in H9c2 Cells: Improvement of Mitochondrial Dysfunction and Activation of GLP-1R and the PI3K/AKT Signaling Pathway.

BACKGROUND/AIMS: Myocardial ischemia/reperfusion injury is a major cause of morbidity and mortality associated with coronary heart disease. Many studies have demonstrated that natural products are promising chemotherapeutic drugs counteracting the loss of cardiomyocytes. Thus, the purpose of the present study was to investigate the effects of geniposide, a traditional Chinese herb extract from Gardenia jasminoides J. Ellis, on cardiomyocyte apoptosis induced by hypoxia/reoxygenation (H/R) in H9c2 cells, and their underlying mechanisms. METHODS: Cell viability and apoptosis ratio were assessed using the cell counting kit-8 assay and Annexin V/propidium iodide (PI) staining. The concentrations of lactate dehydrogenase (LDH), intracellular total superoxide dismutase (T-SOD), and malondialdehyde (MDA) were detected by microplate reader. The production of reactive oxygen species/reactive nitrogen species (ROS/RNS), the level of mitochondrial calcium, and mitochondrial membrane potential depolarization were measured by confocal laser scanning microscopy. Mitochondrial morphology was visualized using transmission electron microscopy. The expressions of Bcl-2 mRNA and Caspase-3 mRNA were measured by reverse transcription-polymerase chain reaction (RT-PCR). The protein levels of cleaved caspase-3, Bcl-2, Bax, AKT, p-AKTserine473, cytochrome-c were detected by western bloting. RESULTS: Geniposide pretreatment increased cell viability, decreased LDH levels in the supernatant, and inhibited cardiomyocyte apoptosis caused by H/R. Furthermore, geniposide reversed mitochondrial dysfunction by decreasing oxidative stress products (ROS/RNS and MDA), increasing anti-oxidative enzyme (T-SOD) level, improving mitochondrial morphology, attenuating mitochondrial calcium overload and blunting depolarization of mitochondrial membrane. Moreover, geniposide pretreatment increased Bcl-2 level and decreased Bax level, thus enhancing the Bcl-2/Bax ratio. Consistent with the above result, Bcl-2 mRNA expression was upregulated and caspase-3 mRNA expression was downregulated by geniposide. In addition, geniposide decreased the protein expression of cleaved caspase-3 and cytochrome-c and increased the level p-AKTserine473. The protective effects of geniposide were partially reversed by glucagon-like pepitide-1 receptor antagonist exendin-(9-39) and the phosphatidylinositol 3 kinase (PI3K) inhibitor LY294002. CONCLUSIONS: Our results suggest that geniposide pretreatment inhibits H/R-induced myocardial apoptosis by reversing mitochondrial dysfunction, an effect in part due to activation of GLP-1R and PI3K/AKT signaling pathway.

[Fever monitoring program in areas with high incidence of typhoid and paratyphoid fever in Guizhou province].

OBJECTIVE: To understand the incidence rates of both typhoid fever and paratyphoid fever in the high prevalent areas of Guizhou province so as to provide evidence for the development of programs on comprehensive intervention and effectiveness evaluation. METHODS: Six townships in Pingba county were selected as intervention areas while six townships in Kaiyang county were taken as control. All hospitals and clinics were classified into A, B and C types according to its level and the capacity of the blood culture. Surveillance on typhoid and paratyphoid fever was conducted based on all population and all hospitals, clinics and county CDCs among the patients with unknown fever. RESULTS: In the surveillance area in those two counties, there were 12 944 blood samples from patients with unknown fever which have been tested and cultured. Among them, 200 strains of Salmonella including 16 typhoid strains, 184 paratyphoid A strains were identified, with the total positive rate as 1.55%. The positive rate before the intervention program was higher than the after. The detection rate was 1.91% in the type A hospitals. 39 strains of Salmonella have been cultured from 2039 samples which accounting for 19.50% (39/200) of the total strains. 4315 blood samples were cultured at the 'Class B' sites which isolated 82 strains of Salmonella, accounting for 41.00% (82/200), with a detection rate as 1.90%. 6590 samples were cultured at the 'Class C' sites, which identified 79 strains of Salmonella, accounting for 39.50% (79/200), with a detection rate as 1.20%. The detection rate was much higher before the use of antibiotics than after using them (P < 0.05). The annual peak time of positive detection was in spring and fall. The outbreaks or epidemics often appeared in the same places, with farmers, students as the high-risk populations. Symptoms of both typhoid and paratyphoid fever were not typical. CONCLUSION: Typhoid and paratyphoid monitoring programs which covered primary health care institutions in the high incidence area seemed to be effective in reflecting the pictures as well as the burden of both typhoid and paratyphoid.

[Assess correlation between bleb morphology at long-term intraocular pressure effect in primary angle-closure glaucoma following trabeculectomy].

OBJECTIVE: To evaluate the correlation between morphologic appearance of blebs at 3 month and long-term intraocular pressure (IOP) effect in patients with primary angle-closure glaucoma (PACG) after trabeculectomy. METHODS: Multi-centered cases series. Data were collected from 176 patients aged ≥ 40 years with PACG who were participated in a randomized clinical trial that aimed at addressing the efficacy of augmented releasable sutures after trabeculectomy. The bleb morphology was graded using the Modified Indian Bleb Appearance Grading Scale (IBAGS) based on standard photos at 3 month after trabeculectomy. IOPs were measured with Goldmann applanation tonometer. The correlation between bleb components and other selected testing influencing factors and long-term IOP was tested by linear Logistic regression analysis. RESULTS: 150 patients (85.7%) completed 18 months of follow up. IOP was (15.6 ± 5.4) mm Hg at 18 month of post-operation. 135 eyes had an IOP ≤ 21 mm Hg without additional medications, 10 eyes ≥ 21 mm Hg, and the remaining 5 eyes required one or two medications to maintain normal IOP. Using IBAGS system, bleb was graded in 142 eyes as follows: H(0) in 3 eyes, H(1) in 45 eyes, H(2) in 90 eyes, and H(3) in 4 eyes, while V(0) was observed in 66 eyes, V(1-3) in 76 eyes. IOP at 18 months in bleb with microcysts was 2.77 mm Hg lower (ß = -2.77, 95%CI = -0.46 to -5.08) than those without microcysts and in bleb with non-vascular was 2.07 mm Hg lower (ß = -2.07, 95%CI = -0.15 to -3.98) than those with vascular at 3 months after surgery. IOP was significantly (ß = -1.20, 95%CI: -0.00 to -2.40) decreased by 1.2 mm Hg with 10 years of age increase (P < 0.05). CONCLUSIONS: Early filtering bleb with microcysts, vascular, and age are identified as important factors to predict long-term IOP effect in patients with PACG after trabeculectomy but not early morphological appearance of filtering bleb.

[Morphological changes of retina after N-methyl-D-aspartate induced damage in rats].

OBJECTIVE: To investigate N-methyl-D-aspartate (NMDA)-induced morphological changes in the retina in rats. METHODS: Thirty-two healthy Sprague-Dawley (SD) rats were randomly divided into 4 groups. Eight rats were in normal control group. The rest 24 rats were equally distributed into 3 experimental groups to receive a single dose of 2 microL intravitreal injection of 3 different concentrations of NMDA (namely 10 nmol, 20 nmol, and 40 nmol per injection ) into the right eyes. The left eyes received 2 microl 0.1 mol PBS used as a self-control. Seven days after the NMDA injection, all rats were killed and the eyes were enucleated. The extent of NMDA-induced neurotoxicity in the retina was quantified by the thickness of the inner plexiform layer (IPL) of the retina at 1.0 - 1.5 mm from the margin of the optic disc of 6 rats in each group. The retinas and optic nerves from the other 2 rats were processed for histopathologic investigation under electronic microscope and light microscope. RESULTS: The thickness of IPL was decreased. There was significant difference between any of the above 2 groups (All P < 0.05). The higher the concentration of NMDA solution, the more decreased thickness of the IPL. No obvious abnormality was observed in the outer layer of the retina. There was degeneration of the optic nerve axons in the NMDA-treated eyes of the experimental groups. The extent of morphological changes of the axons of the optic nerve was related to the dose of NMDA administrated. Ultra-structural study also showed some characteristic changes of apoptosis such as shrunken nucleus and clumping of chromatin at the nuclear membrane in retinal ganglion cell lay (RGCL) and inner nuclear layer (INL). CONCLUSION: Administration of NMDA can result in the thinning of IPL and the dose-dependent degeneration of the optic nerve. Apoptosis may be the main morphological evidence of NMDA receptor-mediated cell death in RGCL and INL in adult rat retinas. NMDA-induced damage is similar to glaucomatous degeneration to some extent.

[The neuroprotective effect of erigeron breviscapus (vant) hand-mazz on retinal ganglion cells after optic nerve crush injury].

OBJECTIVE: To investigate whether a Chinese herbal medicine, erigeron breviscapus (vant) hand-mazz (EBHM), can protect the retinal ganglion cells (RGC) damaged by calibrated optic nerve crush injury. METHODS: Forty-two Sprague-Dawley rats were randomly divided into two groups. Calibrated optic nerve crush injury model was induced in the right eyes by a special designed optic nerve clip. The left eyes served as a control. All 42 rats were randomly divided into 2 groups. Group A consisted of the rats with calibrated optic nerve crush injury and group B consisted of rats with calibrated optic nerve crush injury treated with EBHM. In group B, EBHM solution was given once after the crush injury. According to the time interval between the optic nerve crush and the sacrifice, both groups A and B were further divided into three subgroups (day 4, day 14 and day 21). Therefore, there were 7 rats in each subgroup. Three days before sacrifice, 3% fast blue was injected into superior colliculi bilaterally. The eyes were enucleated after the rat was sacrificed, and flat mounts of the retina from both eyes were prepared on a slide and observed under a fluorescence microscope. Four photos with 400 x magnification were taken from each of the four quadrants of the retina 1 mm away from the optic disc. The labeled RGC were counted by a computerized image analyzer. The labeled RGC rate was used for statistical analysis (the labeled RGC rate = number of RGC in injured eye/control eye x 100%). RESULTS: In group A, the labeled RGC rate was (77.79 +/- 7.11)%, (63.76 +/- 3.79)% and (54.66 +/- 4.75)% on day 4, day 14 and day 21, respectively. In group B, the labeled RGC rate was (80.13 +/- 12.03)%, (78.17 +/- 9.19)% and (83.59 +/- 12.61)% on day 4, day 14 and day 21, respectively. In group B, which was treated with EBHM after injury, the labeled RGC rate was significantly higher than that of group A on day 14 and day 21. CONCLUSIONS: In the experimental optic nerve crush model in rats, EBHM therapy can increase the survival rate of the RGC and can rescue and/or restore the injured RGC.

[Modulation of tracer coupling in AII amacrine cells and ON cone bipolars of rabbit retina by L-arginine].

OBJECTIVE: To determine the relative permeability of the gap junction pathways in AII amacrine cells and ON cone bipolar cells of rabbit retina, and its modulation by L-arginine. METHODS: The distribution of neurobiotin across the heterologous cell assembly was measured using the confocal microscope after microinjecting neurobiotin into a single AII amacrine cell. Modulation of the tracer coupling by 4 mmol/L L-arginine was also observed. Rabbit anti-calretinin antibody was used to stain the retina injected with neurobiotin. RESULTS: Average neurobiotin concentration in the coupled ON cone bipolar cells was lower than that in the coupled AII amacrine cells. L-arginine selectively reduced the concentration of neurobiotin in the ON cone bipolar cells, this effect was more prominent than that observed in the AII amacrine cells (P < 0.05). AII amacrine cells stained with anti-calretinin antibody. CONCLUSIONS: Neurobiotin can pass easily through homologous AII/AII cells gap junctions as compared to the heterologous AII/bipolar cells gap junctions. L-arginine reduces the labeling of neurobiotin in ON cone bipolar cells to a greater degree than in AII amacrine cells. The pathway of this effect is probably by increasing the level of cGMP and acting at the bipolar cell side of this gap junction.

[Clinical efficacy of 0.2% brimonidine in patients with open-angle glaucoma or ocular hypertension].

OBJECTIVE: To evaluate the efficacy and safety of 0.2% brimonidine administered in patients with glaucoma or ocular hypertension. METHODS: Twenty-five patients (41 eyes) with primary open-angle glaucoma or ocular hypertension were enrolled in this prospective study. Eye drops of 0.2% brimonidine were used twice daily for 6 months and the patients were examined every month after the treatment, including the trough intraocular pressure (IOP, IOP 12 h after 0.2% brimonidine was administrated) and the peak IOP (IOP 12 h after 0.2% brimonidine was administrated). The visual field was examined every three months. RESULTS: The use of 0.2% brimonidine significantly lowered the trough IOP and the peak IOP (P < 0.05). Every point of the IOP diurnal curve significantly decreased compared with the baseline (P < 0.05). The visual field had no significant change 3 months or 6 months after the treatment with 0.2% brimonidine. No serious systemic side effect was observed. CONCLUSION: Brimonidine is safe and effective in lowering IOP in glaucoma or ocular hypertension and is well tolerated.