Saikosaponin D Alleviates DOX-induced Cardiac Injury In Vivo and In Vitro.

ABSTRACT: As a highly efficient anticancer agent, doxorubicin (DOX) is used for treatment of various cancers, but DOX-induced oxidative damages contribute to a degenerative irreversible cardiac toxicity. Saikosaponin D (SSD), which is a triterpenoid saponin with many biological activities including anti-inflammatory effects and antioxidant properties, provides protection against pathologic cardiac remodeling and fibrosis. In the present study, we investigated the work of SSD for DOX-induced cardiotoxicity and the involved mechanisms. We observed that DOX injection induced cardiac injury and malfunction and decreased survival rate. Besides, DOX treatment increased lactate dehydrogenase leakage, cardiomyocyte apoptosis, and myocardium fibrosis and decreased the size of cardiomyocytes. Meanwhile, all the effects were notably attenuated by SSD treatment. In vitro, we found that 1 µM SSD could enhance the proliferation of H9c2 cells and inhibit DOX-induced apoptosis. It was found that the levels of malondialdehyde (MDA) and reactive oxygen species were significantly reduced by improving the activities of the endogenous antioxidative enzymes including catalase and glutathione peroxidase. Furthermore, SSD treatment could downregulate the DOX-induced p38 phosphorylation. Our results suggested that SSD efficiently protected the cardiomyocytes from DOX-induced cardiotoxicity by inhibiting the excessive oxidative stress via p38-MAPK (mitogen-activated protein kinase, MAPK) signaling pathway.

Synthesis of 4-chalcogenyl pyrazoles via electrophilic chalcogenation/cyclization of α,ß-alkynic hydrazones.

A facile method for the synthesis of 4-chalcogenylated pyrazoles has been developed via electrophilic chalcogenation/cyclization of α,ß-alkynic hydrazones. The cyclization of α,ß-alkynic aldehyde hydrazones could be induced by using either sulfenyl chloride or the S-electrophiles generated in situ from the reaction of NCS and arythiol. The developed method was successfully applied to the synthesis of the sulfenyl analogue of celecoxib.

Synthesis of 4-Sulfenyl Isoxazoles through AlCl3-Mediated Electrophilic Cyclization and Sulfenylation of 2-Alkyn-1-one O-Methyloximes.

An efficient method for the synthesis of 4-sulfenyl isoxazoles has been developed via AlCl3-mediated electrophilic cyclization/sulfenylation of 2-alkyn-1-one O-methyloximes. Remarkably, N-arylsulfanylsuccinimides are employed as electrophiles for the construction of 4-arylsulfanyl isoxazoles, and 4-alkylsulfanyl isoxazoles are accessed with dialkyl disulfides as electrophiles.

Copper(II)-Catalyzed Four-Component Oxysulfonylation/Diazenylation: Synthesis of α-Arylhydrazo-ß-keto Sulfones.

A new and convenient method for one-pot synthesis of α-arylhydrazo-ß-keto sulfones is developed via Cu (II)-catalyzed oxysulfonylation/diazenylation of alkenes. This four-component cascade reaction enables a series of α-arylhydrazo-ß-keto sulfone derivatives accessed from readily available alkenes, sulfinates, and diazonium salts under aerobic conditions. Furthermore, the 3-sulfonyl cinnolin-4(1 H)-one skeleton is successfully constructed from the corresponding α-arylhydrazo-ß-keto sulfone product under basic conditions.

AlCl3-Catalyzed Intramolecular Cyclization of N-Arylpropynamides with N-Sulfanylsuccinimides: Divergent Synthesis of 3-Sulfenyl Quinolin-2-ones and Azaspiro[4,5]trienones.

Switchable ortho/ipso-cyclization of N-arylpropynamides induced with N-sulfanylsuccinimides as general sulfur reagents is reported. In the presence of MeOH, para-fluoro N-arylpropynamides exclusively undergo the ipso-cyclization to give 3-sulfenyl azaspiro[4,5]trienones. Two kinds of bioactive heterocycles, benzothieno-[3,2-b]quinoline and -[2,3-c]quinolone, have been directly and efficiently prepared from the corresponding sulfenylated products.

Evaluation of three-dimensional high-resolution magnetic resonance imaging in the diagnosis of intracranial atherosclerotic stenosis / Evaluación de resonancia magnética tridimensional de alta resolución en el diagnóstico de la estenosis aterosclerótica intracraneal

SUMMARY: Intracranial artery stenosis (ICAS) was one of the main causes of ischemic stroke onset and recurrence. About 30 % of strokes were caused by intracranial artery stenosis. Intracranial artery stenosis had a high incidence in China and faced a high risk of recurrence for a long time. It affected patient safety and quality of life seriously. At the same time, it caused a heavy financial burden for the patient´s family. Therefore, early detection and accuracy of intracranial artery stenosis evaluation were extremely important. High-resolution magnetic resonance imaging (HR-MRI) had been widely used in clinical examinations, making up for the shortcomings of traditional vascular imaging methods that could only show the degree of luminal stenosis, making it possible to perform lumens, tube wall and plaque features of atherosclerotic intracranial arteries at the same time. There were still some controversies about the credibility of this technique in assessing the intracranial artery lumen stenosis. This article reviewed the application efficacy of HR-MRI technology in evaluating the degree of intracranial atherosclerotic stenosis.

RESUMEN: La estenosis de arterias intracraneales (ICAS) es una de las principales causas del ictus isquémico, como así también de su recurrencia. Alrededor del 30 % de los ataques cerebrovasculares son causados por estenosis de la arteria intracraneal. La estenosis de arterias intracraneales tiene una alta incidencia en China y enfrenta un alto riesgo de recurrencia, afectando gravemente la seguridad y la calidad de vida de los pacientes. Al mismo tiempo, supone una importante carga financiera para la familia de los pacientes. Por lo tanto, la detección temprana y la precisión de la evaluación de la estenosis de arterias intracraneales es extremadamente importante. La resonancia magnética de alta resolución (HR-MRI, por sus siglas en inglés) es utilizada ampliamente en los exámenes clínicos, compensando las deficiencias de los métodos tradicionales de imágenes vasculares que solo pueden mostrar el grado de estenosis luminal, haciendo posible el estudio de las características del lumen, pared vascular y la placa ateroesclerótica, de las arterias intracraneales afectadas, al mismo tiempo. Aún existen algunas controversias sobre la credibilidad de esta técnica en la evaluación de la estenosis del lumen de arterias intracraneales. En este artículo se revisó la eficacia de la aplicación de la tecnología HR-MRI para evaluar el grado de estenosis aterosclerótica intracraneal.

Decreased expression of mitochondrial genes in human unfertilized oocytes and arrested embryos.

OBJECTIVE: To evaluate the relationship between mitochondrial gene expression of oocytes/embryos and their fertilizability in unfertilized oocytes, arrested embryos, and tripronucleate zygotes, because both nuclear and cytoplasmic factors contribute to oocyte activation, fertilization, and subsequent development. DESIGN: Prospective laboratory research. SETTING: In vitro fertilization (IVF) laboratory in a university hospital. PATIENT(S): Seventy-five unfertilized oocytes, 45 arrested embryos, and 24 tripronucleate (3PN) embryos from 45 female patients undergoing IVF. INTERVENTION(S): Analysis of mitochondrial gene expression by semiquantitative reverse transcription polymerase chain reaction (RT-PCR). MAIN OUTCOME MEASURE(S): Comparison of the expression levels of mitochondrial genes including ND2, CO I, CO II, ATPase 6, CO III, ND3, ND6, and Cyt b in three groups. RESULT(S): Significantly decreased transcription levels were expressed in unfertilized oocytes and arrested embryos. The average expression levels of the eight determined genes compared with the control (GAPDH) was 4.4 +/- 0.7, 6.4 +/- 1.1, and 13.2 +/- 1.1 in unfertilized oocytes, arrested embryos, and 3PN embryos, respectively. Significantly decreased expressions of the ATPase 6, CO III, and ND3 genes were detected from samples with 4977-bp common deletion in the mitochondrial DNA (mtDNA) compared with the non-deletion group. CONCLUSION(S): The present study is the first report to present globally decreased mitochondrial gene expression levels in human compromised oocytes and embryos. These data support the notion that the down-regulation of mitochondrial RNA by defective oxidative phosphorylation genes possibly affects oocyte quality including fertilization and further embryo development.

Global analysis of differentially expressed genes in early gestational decidua and chorionic villi using a 9600 human cDNA microarray.

The global gene expression profiles of the decidua and chorionic villi of early human pregnancies were analysed by using cDNA microarray technology. Decidual and villous placental tissues were obtained from first trimester abortus and mRNA was extracted for cDNA microarray analysis. The human cDNA microarray [9600 clones, including known regulatory genes and expressed sequence tags (EST)] with colorimetric detection was used to identify differentially expressed genes between early gestational decidua and villi. According to cDNA microarray analysis, we have identified 641 genes with highly expressed mRNA in both decidua and villi, 49 genes with higher expressions in decidua, and 75 genes with higher expression in chorionic villi. These differentially expressed genes were further grouped into categories by their putative functions, including: cell growth-related factors, hormones/cytokines, cell adhesion molecules, signal transduction molecules, apoptosis-related factors, cytoskeleton/extracellular matrix proteins, and EST. Immunohistochemical stainings of cathepsin L, leukaemia inhibitory factor-receptor, and proliferative cell nuclear antigen showed results consistent with the microarray data. Identification of the differentially expressed genes between decidua and villi by microarray provide a global profiling of the gene expression pattern. This work adds to our understanding of placentation by reporting the gene expression profiles during first trimester human pregnancies using cDNA microarray.