RESUMEN
One rare stephacidin-asperochratide hybrid, stephaochratidin A (1), was isolated from the deep-sea-derived Aspergillus ochraceus MCCC 3A00521. The relative structure of 1 was determined by comprehensive analyses of its 1D and 2D NMR data as well as HRESIMS data. And the absolute configuration was unambiguously assigned by ECD calculations and the X-ray single-crystal diffraction analysis. Plausible biosynthetic pathway of 1 was proposed. Stephaochratidin A (1) exhibited significant ferroptosis inhibitory activity with the EC50 value of 15.4 µM by downregulating HMOX-1 expression and lipid peroxidation.
Asunto(s)
Aspergillus ochraceus , Ferroptosis , Ferroptosis/efectos de los fármacos , Estructura Molecular , Aspergillus ochraceus/química , Humanos , Peroxidación de Lípido/efectos de los fármacosRESUMEN
OBJECTIVE: To investigate the safety and effect of injecting heparin into hematoma on peri-hematoma edema and hematoma volume in pigs with intracerebral hemorrhage (ICH). METHODS: Thirteen sucking pigs were divided randomly into two groups: hemorrhage group, in which 2.5 ml arterial blood was injected into the right frontal lobe and heparin group, in which 0.2 ml of heparin was injected into the hematoma produced by the injection of 2.3 ml of blood into the similar site. The hematoma volume and peri-hematoma edema were determined by the sequences of T2* weighted image (T2*WI), fluid-attenuated inversion- recovery (FLAIR) image and diffusion weighted image (DWI) by 1.5 T magnetic resonance image (MRI) from 30-60 minutes afterwards to 24 hours. The peri-hematoma apparent diffusion coefficient (ADC) was compared with that of contralateral hemisphere, and the corresponding histologic changes were studied. RESULTS: The average volume, shown by T2*WI at 24 hours, was significantly larger than that at 30-60 minutes after hematoma formation in hemorrhagic group [(5.29+/-0.98) cm3 vs. (3.09+/-0.38) cm3, P<0.01]. But there was no significant change in hematoma volume in hemorrhagic group from 30-60 minutes on to 24 hours [(2.21+/-0.28) cm3 vs. (2.33+/-0.30) cm3, P>0.05]. Both increased and decreased ADC were found around the hematoma in some animals of the heparin group compared with that of the contralateral hemisphere. On the other hand, in hemorrhagic group, only increased ADC could be found around the lesion, and there was no decreased ADC. CONCLUSION: Injection of heparin into an intracerebral hematoma leads to enlargement of the hematoma and more marked peri-lesion edema. On ADC maps, enlargement of hematoma is attributed to the edema around the lesion leading to injury to the brain tissue.
Asunto(s)
Hemorragia Cerebral/patología , Edema/patología , Hematoma/patología , Heparina/farmacología , Animales , Hemorragia Cerebral/complicaciones , Modelos Animales de Enfermedad , Edema/etiología , Femenino , Hematoma/complicaciones , Heparina/administración & dosificación , Inyecciones Intralesiones , Masculino , Distribución Aleatoria , PorcinosRESUMEN
OBJECTIVE: To look for a gene delivery route to the treatment of Duchenne muscular dystrophy(DMD). METHODS: The recombinant adeno-associated virus vector(rAAV) carrying a LacZ reporter gene was constructed. rAAVLacZ was delivered into the skeletal muscle tissue of C57/BL6 mice by intramuscular injection. Then an intraarterial delivery route was taken to reveal whether rAAVLacZ could transduce muscle tissue. RESULTS: (1) The LacZ gene was efficiently transduced and expressed persisting for 5 months after intramuscular injection. (2) The membrane of muscle and smooth muscle of vessel was widely transduced by intra-arterial delivery rAAVLacZ. CONCLUSION: These data provide the evidence that rAAVLacZ can efficiently transduce muscle for a long period. Improving intraarterial gene delivery will be promising means for rAAV-mediated gene therapy for generalized skeletal muscle of DMD.
Asunto(s)
Dependovirus/genética , Genes Reporteros , Operón Lac/fisiología , Músculo Esquelético/metabolismo , Animales , Línea Celular , Embrión de Mamíferos , Expresión Génica , Vectores Genéticos , Humanos , Inyecciones Intramusculares , Riñón/citología , Riñón/metabolismo , Ratones , Ratones Endogámicos C57BL , Músculo Esquelético/citología , Proteínas Recombinantes/metabolismo , Transfección/métodosRESUMEN
OBJECTIVE: Duchenne muscular dystrophy (DMD) is the most common and letal genetic skeletal muscle disorder, caused by recessive mutations in the dystrophin gene and no treatment is available. The present paper is aimed to study if recombinant adeno-associated virus vector (rAAV) mediated dystrophin minigene SMCKA3999 could effectively ameliorates dystrophic pathology in mdx model mice. METHODS: We used dystrophin minigene SMCKA3999 to construct rAAVSMCKA3999. When injected into the skeletal muscle of mdx mice (DMD model), we adopted methods of immunofluorescent (IF) staining, Evans Blue and electromicroscopy to observe if rAAVSMCKA3999 could effectively ameliorates dystrophic pathology in mdx model mice. RESULTS: rAAVSMCK3999 resulted in efficient and stable expression and restoration of the missing dystrophin onto the plasma membrane. rAAVSMCKA3999 can also protect myofiber membrane integrity. For the first time we prove that rAAVSMCKA3999 can improve ultrastructure changes of DMD. CONCLUSION: We have demonstrated the effectiveness of rAAVSMCKA3999 in correcting pathology changes of skeletal muscle, which offer a promising avenue for DMD gene therapy.