RESUMEN
The antibacterial secondary metabolites of the fungus Penicillium chrysogenum associated with the beetle Aspongopus chinensis were investigated through chromatographic fractionation methods of ethyl acetate extracts of the fungal cultures. Five compounds were isolated, and their structures were determined as emodin, 4-(methoxymethyl)benzoic acid, isoochracinic acid, secalonic acid D, and dicerandrol A using mass spectroscopy and nuclear magnetic resonance spectroscopic analyses. Emodin exhibited strong antimicrobial activity, especially against Staphylococcus aureus even when growing on cooked pork, with a minimal inhibitory concentration (MIC) of 6.3 µg/mL. Dimeric tetrahydroxanthones, such as secalonic acid D and dicerandrol A, also exhibited potent activity, with MIC values ranging from 9.5 to 28.5 µg/mL. In summary, P. chrysogenum was isolated as a symbiotic fungus of the beetle A. chinensis for the first time and this strain could generate antibacterial secondary metabolites, which could potently inhibit gram-positive bacteria growth in vitro.
Asunto(s)
Escarabajos , Emodina , Penicillium chrysogenum , Penicillium , Animales , Penicillium chrysogenum/química , Antibacterianos , Staphylococcus aureus , Pruebas de Sensibilidad MicrobianaRESUMEN
BACKGROUND: Retinal neurodegeneration is induced by a variety of environmental insults and stresses, but the exact mechanisms are unclear. In the present study, we explored the involvement of cytosolic mitochondrial DNA (mtDNA), resulting in the cGAS-STING dependent inflammatory response and apoptosis in retinal damage in vivo. METHODS: Retinal injury was induced with white light or intravitreal injection of lipopolysaccharide (LPS). After light- or LPS-induced injury, the amount of cytosolic mtDNA in the retina was detected by PCR. The mtDNA was isolated and used to transfect retinas in vivo. WB and real-time PCR were used to evaluate the activation of cGAS-STING pathway and the levels of apoptosis-associated protein at different times after mtDNA injection. Retinal cell apoptosis rate was detected by TUNEL staining. Full-field electroretinography (ERG) was used to assess the retinal function. RESULTS: Light injury and the intravitreal injection of LPS both caused the leakage of mtDNA into the cytoplasm in retinal tissue. After the transfection of mtDNA in vivo, the levels of cGAS, STING, and IFN-ß mRNAs and the protein levels of STING, phosph-TBK1, phospho-IRF3, and IFN-ß were upregulated. mtDNA injection also induced the activation of caspase 3 and caspase 9. BAX and BAK were increased at both the mRNA and protein levels. The release of cytochrome c from the mitochondria to the cytosol was increased after mtDNA injection. The wave amplitudes on ERG decreased and retinal cell apoptosis was detected after mtDNA injection. CONCLUSIONS: Cytosolic mtDNA triggers an inflammatory response. It also promotes apoptosis and the dysfunction of the retina.
Asunto(s)
ADN Mitocondrial , Lipopolisacáridos , Animales , ADN Mitocondrial/genética , Inyecciones Intravítreas , Proteínas de la Membrana/metabolismo , Mitocondrias , Nucleotidiltransferasas/genética , Nucleotidiltransferasas/metabolismo , RatasRESUMEN
BACKGROUND: Retinal neurodegeneration is induced by a variety of environmental insults and stresses, but the exact mechanisms are unclear. In the present study, we explored the involvement of cytosolic mitochondrial DNA (mtDNA), resulting in the cGAS-STING dependent inflammatory response and apoptosis in retinal damage in vivo. METHODS: Retinal injury was induced with white light or intravitreal injection of lipopolysaccharide (LPS). After light-or LPS-induced injury, the amount of cytosolic mtDNA in the retina was detected by PCR. The mtDNA was isolated and used to transfect retinas in vivo. WB and real-time PCR were used to evaluate the activation of cGAS-STING path-way and the levels of apoptosis-associated protein at different times after mtDNA injection. Retinal cell apoptosis rate was detected by TUNEL staining. Full-field electroretinography (ERG) was used to assess the retinal function. RESULTS: Light injury and the intravitreal injection of LPS both caused the leakage of mtDNA into the cytoplasm in retinal tissue. After the transfection of mtDNA in vivo, the levels of cGAS, STING, and IFN-ß mRNAs and the protein levels of STING, phosph-TBK1, phospho-IRF3, and IFN-ß were upregulated. mtDNA injection also induced the activation of caspase 3 and caspase 9. BAX and BAK were increased at both the mRNA and protein levels. The release of cytochrome c from the mitochondria to the cytosol was increased after mtDNA injection. The wave amplitudes on ERG decreased and retinal cell apoptosis was detected after mtDNA injection. CONCLUSIONS: Cytosolic mtDNA triggers an inflammatory response. It also promotes apoptosis and the dysfunction of the retina.
Asunto(s)
Animales , Ratas , ADN Mitocondrial/genética , Lipopolisacáridos , Inyecciones Intravítreas , Proteínas de la Membrana/metabolismo , Mitocondrias , Nucleotidiltransferasas/genética , Nucleotidiltransferasas/metabolismoRESUMEN
Acetaminophen (APAP) overdose is one of the leading causes of hepatotoxicity and acute liver failure in the United States. Accumulating evidence suggests that hepatocyte necrosis plays a critical role in APAP-induced liver injury (AILI). However, the mechanisms of APAP-induced necrosis and liver injury are not fully understood. In this study, we found that p53 up-regulated modulator of apoptosis (PUMA), a B-cell lymphoma-2 (Bcl-2) homology domain 3 (BH3)-only Bcl-2 family member, was markedly induced by APAP in mouse livers and in isolated human and mouse hepatocytes. PUMA deficiency suppressed APAP-induced mitochondrial dysfunction and release of cell death factors from mitochondria, and protected against APAP-induced hepatocyte necrosis and liver injury in mice. PUMA induction by APAP was p53 independent, and required receptor-interacting protein kinase 1 (RIP1) and c-Jun N-terminal kinase (JNK) by transcriptional activation. Furthermore, a small-molecule PUMA inhibitor, administered after APAP treatment, mitigated APAP-induced hepatocyte necrosis and liver injury. Conclusion: Our results demonstrate that RIP1/JNK-dependent PUMA induction mediates AILI by promoting hepatocyte mitochondrial dysfunction and necrosis, and suggest that PUMA inhibition is useful for alleviating acute hepatotoxicity attributed to APAP overdose.
Asunto(s)
Acetaminofén/envenenamiento , Analgésicos no Narcóticos/envenenamiento , Proteínas Reguladoras de la Apoptosis/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Proteínas Supresoras de Tumor/metabolismo , Animales , Proteínas Reguladoras de la Apoptosis/antagonistas & inhibidores , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Evaluación Preclínica de Medicamentos , Proteínas Activadoras de GTPasa/metabolismo , Hígado/ultraestructura , Sistema de Señalización de MAP Quinasas , Masculino , Ratones Noqueados , Proteínas Supresoras de Tumor/antagonistas & inhibidoresRESUMEN
A 73-year-old man presented with fatigue and weight loss. He had CT-proven splenic mass with fistulous connection to the greater curvature of the stomach, which suggested abscess. FDG PET/CT confirmed gastrosplenic fistula in addition to active lymph nodes in the gastrohepatic ligament and epigastric region. Pathological examination after the biopsy of the spleen was consistent with diffuse large B-cell lymphoma. Chemotherapy was administered with close clinical follow-up and resulted in the resolution of fistula without requirement for surgery.
Asunto(s)
Fístula/diagnóstico por imagen , Fístula/etiología , Fluorodesoxiglucosa F18 , Linfoma/complicaciones , Tomografía Computarizada por Tomografía de Emisión de Positrones , Bazo , Estómago , Anciano , Humanos , MasculinoRESUMEN
A 68-year-old man with a history of malignant melanoma in the right axilla underwent FDG PET/CT. The images demonstrated a focally increased activity in the subcutaneous tissue anterior to the distal left tibia, suggestive of metastasis. However, a gouty tophus was diagnosed pathologically after biopsy.