Tuberous sclerosis complex (TSC) is a tumor suppressor syndrome characterized by benign tumors in multiple organs, including the brain and kidney. TSC-associated tumors exhibit hyperactivation of mammalian target of rapamycin complex 1 (mTORC1), a direct inhibitor of autophagy. Autophagy can either promote or inhibit tumorigenesis, depending on the cellular context. The role of autophagy in the pathogenesis and treatment of the multisystem manifestations of TSC is unknown. We found that the combination of mTORC1 and autophagy inhibition was more effective than either treatment alone in inhibiting the survival of tuberin (TSC2)-null cells, growth of TSC2-null xenograft tumors, and development of spontaneous renal tumors in Tsc2 +/− mice. Down-regulation of Atg5 induced extensive central necrosis in TSC2-null xenograft tumors, and loss of one allele of Beclin1 almost completely blocked macroscopic renal tumor formation in Tsc2 +/− mice. Surprisingly, given the finding that lowering autophagy blocks TSC tumorigenesis, genetic down-regulation of p62/sequestosome 1 (SQSTM1), the autophagy substrate that accumulates in TSC tumors as a consequence of low autophagy levels, strongly inhibited the growth of TSC2-null xenograft tumors. These data demonstrate that autophagy is a critical component of TSC tumorigenesis, suggest that mTORC1 inhibitors may have autophagy-dependent prosurvival effects in TSC, and reveal two distinct therapeutic targets for TSC: autophagy and the autophagy target p62/SQSTM1.utophagy is increasingly recognized to play a critical role in tumor development and cancer therapy (1, 2). In autophagy, cells undergo membrane rearrangement to sequester a portion of cytoplasm, organelles, and intracellular proteins for delivery to a degradative lysosome for recycling. In situations of bioenergetic stress, autophagy promotes the survival of established tumors by supplying metabolic precursors; however, excessive autophagy has been associated with cell death (3, 4). Inhibition of autophagy using chloroquine (CQ), which blocks lysosomeautophagosome fusion and lysosomal protein degradation (5), suppresses the growth of Myc-induced lymphomas (6). In other situations, however, inhibition of autophagy promotes tumorigenesis; for example, haploinsufficinecy for the autophagy gene Beclin1 promotes tumorigenesis in mouse models (7,8), and allelic loss of Beclin1 is associated with human breast, ovarian, and prostate cancers (1).Tuberous sclerosis complex (TSC) is an autosomal dominant tumor suppressor gene syndrome caused by germline mutations in the TSC1 or TSC2 genes (9). Patients with TSC have multisystem manifestations, which can include neurologic disease (i.e., seizures, mental retardation, and autism), benign tumors in multiple organs, and pulmonary lymphangioleiomyomatosis (LAM).The TSC1-TSC2 protein complex acts as a cellular sensor, integrating signals from growth factors (10), hypoxia (11, 12), ATP availability (13), IκB kinase (IKK) (14), and the cell cycle (15) through direct phosphorylation by kinases ...

Viral infections can cause serious diseases for humans and animals. Accurate and early detection of viruses is often crucial for clinical diagnosis and therapy. Aptamers are mostly single-stranded nucleotide sequences that are artificially synthesized by an in vitro technology known as the Systematic Evolution of Ligands by Exponential Enrichment (SELEX). Similar to antibodies, aptamers bind specifically to their targets. However, compared with antibody, aptamers are easy to synthesize and modify and can bind to a broad range of targets. Thus, aptamers are promising for detecting viruses and treating viral infections. In this review, we briefly introduce aptamer-based biosensors (aptasensors) and describe their applications in rapid detection of viruses and as antiviral agents in treating infections. We summarize available data about the use of aptamers to detect and inhibit viruses. Furthermore, for the first time, we list aptamers specific to different viruses that have been screened out but have not yet been used for detecting viruses or treating viral infections. Finally, we analyze barriers and developing perspectives in the application of aptamer-based virus detection and therapeutics.

Enterovirus A71 (EV-A71) infection has grown to become a serious threat to global public health. It is one of the major causes of hand, foot, and mouth disease (HFMD) in infants and young children. EV-A71 can also infect the central nervous system (CNS) and induce diverse neurological complications, such as brainstem encephalitis, aseptic meningitis, and acute flaccid paralysis, or even death. Viral proteins play a crucial role in EV-A71 infection. Many recent studies have discussed the structure and function of EV-A71 proteins, and the findings reported will definitely aid the development of vaccines and therapeutic approaches. This article reviews the progress in the research on the structure and function of EV-A71 proteins. Available literature can provide a basis for studying the pathogenesis of EV-A71 infection in detail.

Exosomes are small secreted cellular vesicles for intercellular communications which contain proteins, mRNAs, and microRNAs (miRNAs). Recent studies have shown that exosomes play an important role in the transmission of infectious agents including hepatitis C virus, human immunodeficiency virus, and so on. However, the role of exosomes in the transfer of enterovirus 71 (EV71) between host cells remains unknown. In this study, we show that the exosomes derived from EV71-infected rhabdomyosarcoma cells contain EV71 RNA and capsid protein VP1, determined by quantitative reverse transcription-PCR (QRT-PCR) and Western blot analysis. The shedding of exosomes containing virus can establish a productive infection in human neuroblastoma cell line (SK-N-SH). A comparative analysis of neutralization by EV71-specific immunoglobulins showed different levels of neutralization of exosomes-mediated infection compared with free virus. In conclusion, exosomes from EV71-infected cells may play an important role in virus dissemination and are partially resisted to antibody neutralization. Our results suggest that there is an exosomal route of EV71 transmission infection.