Severe sepsis associated with overproduction of tumor necrosis factor α and reactive oxygen species leads to energy depletion and cellular damage. Both reactive oxygen species and damaged organelles induce autophagy for recycling nutrients to combat pathological stress. To study whether autophagy plays a beneficial role in the pathogenesis of renal failure during sepsis, rats were subjected to cecal ligation and puncture (CLP) or sham operation. Temporal relationship of autophagy and renal dysfunction were examined in vivo. The results showed that the level of lipidated microtubule-associated protein light chain 3 (LC3-II), a marker of autophagy, elevated transiently at 3 h but declined at 9 h until 18 h after CLP. Light chain 3 aggregation in renal tissue showed a similar trend to the change of LC3-II protein. High levels of blood urea nitrogen and creatinine as well as low tubular sodium reabsorption occurred at 18 h after CLP. The distribution of autophagy located primarily in angiotensin-converting enzyme-positive, which is concentrated in proximal tubule, but calbindin D28k (calcium-binding protein D28K, a marker of distal tubule)-negative cells in renal cortex. Therefore, NRK-52E (proximal tubule epithelial cell line) cells were used to further examine cell viability and DNA fragmentation after silencing or inducing autophagy. We found that knockdown of Atg7 (autophagy-related gene 7) exaggerates, whereas preincubation of rapamycin (an autophagy inducer) diminishes tumor necrosis factor α-induced cell death. These results suggest that the decline of sepsis-induced autophagy contributes to the proximal tubular dysfunction, and maintenance of sufficient autophagy prevents cell death. These data open prospects for therapies that activate autophagy during sepsis.

Choline can be reliably detected in large malignant bone and soft-tissue tumors by using a multiecho point-resolved spectroscopic protocol. 1H MR spectroscopy can help differentiate malignant from benign musculoskeletal tumors by revealing the presence or absence of water-soluble choline metabolites.

Autophagy is deficient presumably due to suppression by high Akt-mTOR activity in nasal polyps, which may provide a molecular basis for future mechanistic study of the disease.

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The present study was designed to identify possible signaling pathways, which may play a role in prevention of neuronal apoptosis in the sexually dimorphic nucleus of the preoptic area (SDN-POA) after physiological activation of the N-methyl-D-aspartate (NMDA) receptor. Gene response to the blockage of the NMDA receptor by an antagonist (dizocilpine hydrogen maleate; MK-801) was screened after suppression subtractive hybridization (SSH). The results showed that dfferential screening after SSH detected the presence of some neurotrophic genes (RNA binding motif protein 3 (RBM3), -tubulin) as well as apoptosis-related genes (Bcl-2, cytochrome oxidase subunit II, cytochrome oxidase subunit III) in the SDN-POA of male rats, which were down-regulated by blocking the NMDA receptor. The RT-PCR products of the aforementioned genes in MK-801-treated males were significantly less than that in untreated males. In particular, the expression of Bcl-2 mRNA, including Bcl-2 protein, in male rats were significantly suppressed by MK-801 treatment. Moreover, the binding activity of nuclear factor B (NF B) was significantly higher in male rats than in females, but significantly diminished by blocking the NMDA receptor with MK-801 in male rats. No significant difference in cAMP response element-binding protein (CREB) binding activity was observed among untreated male, MK-801-treated male, untreated female and MK-801-treated female groups. These results suggest that genes regulated by NMDA receptor activation might participate in neuronal growth and/or anti-apoptosis, and support an important signaling pathway of NF B activation and its target gene, Bcl-2, in preventing neuronal apoptosis in the SDN-POA of male rats during sexual development.