Newcastle disease virus (NDV) has been previously shown to possess oncolytic activity, causing specific lysis of cancerous but not normal cells. Here we show that despite these findings, the oncolytic efficiency of naturally occurring NDV strains can still be relatively low, as many tumors exhibit strong innate immune responses that suppress viral replication and spread. To overcome this problem, we generated a recombinant fusogenic NDV expressing influenza NS1 protein, a protein exhibiting interferon (IFN)-antagonist and antiapoptotic functions in human and mouse cells. Interestingly, the resultant virus was dramatically enhanced in its ability to form syncytia, lyse a variety of human and mouse tumor cell lines, and suppressed the induction of the cellular IFN responses. Using the aggressive syngeneic murine melanoma model, we show that the NDV-NS1 virus is more effective than virus not expressing NS1 in clearing the established footpad tumors and results in higher overall long-term animal survival. In addition, mice treated with NDV-NS1 exhibited no signs of toxicity to the virus and developed tumor-specific cytotoxic T lymphocyte (CTL) responses. These findings demonstrate that modulation of innate immune responses by NDV results in enhancement of its oncolytic properties and warrant further investigation of this strategy in design of oncolytic NDV vectors against human tumors.
Abstract Background Exosomes are vesicles secreted by all types of mammalian cells. They are characterized by a double‐layered lipid membrane structure. They serve as carriers for a plethora of signal molecules, including DNA, RNA, proteins, and lipids. Their unique capability of effortlessly crossing the blood–brain barrier underscores their critical role in the progression of various neurological disorders. This includes, but is not limited to, diseases such as Alzheimer's, Parkinson's, and ischemic stroke. Establishing stable and mature methods for isolating exosomes is a prerequisite for the study of exosomes and their biomedical significance. The extraction technologies of exosomes include differential centrifugation, density gradient centrifugation, size exclusion chromatography, ultrafiltration, polymer coprecipitation, immunoaffinity capture, microfluidic, and so forth. Each extraction technology has its own advantages and disadvantages, and the extraction standards of exosomes have not been unified internationally. Aims This review aimed to showcase the recent advancements in exosome isolation techniques and thoroughly compare the advantages and disadvantages of different methods. Furthermore, the significant research progress made in using exosomes for diagnosing and treating central nervous system (CNS) diseases has been emphasized. Conclusion The varying isolation methods result in differences in the concentration, purity, and size of exosomes. The efficient separation of exosomes facilitates their widespread application, particularly in the diagnosis and treatment of CNS diseases.
This paper presents the results of a study on the nest site selection of the Daurian Partridge Perdix dauuricae in Ningwu County of Shanxi Province from 1991 to 1993.Totally 60 nests have been found in the field work,with most of them were located in the farmland and shruby areas.About 67% of the nests built in the sunny southeastern slope and southwestern slope.The comparisons of the 12 habitat variables which may affect nesting success between the nest sites and random chosen non-nest sites within 100 m from the nest show that,5 variables influenced the nest site selection of the Daurian Partridge are (in decreasing order of importance):the amount of leaf litter,the width of field boundary,the amount of dead grass,the width of shrub and the height of the bank at the base of the field boundary.The results of discriminant analysis indicate that,the amount of leaf litter and the amount of dead grass are the two most important variables distinct the nest sites and non-nest sites.In conclusion,the Daurian Partridge prefer to select the site in the farmland and shruby areas which have more leaf litter and dead grass combined with relative higher vegetation coverage to build its nest.
Cerebral ischemia is characterized by inadequate blood supply to the brain to fulfill its metabolic demand. It is a leading cause of stroke. The objective of this study aimed to elucidate the effects of ethanolic extract of Siegesbeckia pubescens (EESP) Makino against cerebral ischemia in rats. Sixty male Sprague-Dawley (SD) rats were distributed into 5 groups (n = 12) viz., low dose (2.5 g/kg/day) EESP group, high dose (5 g/kg/day) EESP group, Nimodipine group, untreated control, and sham-operated control. The reference group received 16 mg/kg/day of nimodipine, while the untreated and sham-operated control was given 20 ml/kg of distilled water. The middle cerebral artery occlusion (MCAO) induced focal cerebral ischemia. On the 7th day of the trial, neurological evaluation and biochemical assays were carried out. After that, rats were sacrificed, and the brain infarct area was analyzed with image processing software. The extent of neurologic deficits, infarct area, concentration of superoxide dismutase (SOD), and malondialdehyde (MDA) was significantly altered by the EESP when compared with untreated control and Sham-operated control. Taken together, these results reported protective effects of EESP on cerebrovascular ischemia that perhaps correlate with its mechanism of free radical scavenging. Our findings may provide insight into treating cerebral ischemia and give a new research era for further study.
Deep Science is an innovative intelligent digital platform for international researcher. Combining preprint hosting and open peer review with intelligence, Deep Science aims to be the leading publishing venue for scholarly research worldwide.
'/%3e%3cuse xlink:href='%23a' transform='rotate(23.036 .093 25.536)'/%3e%3cuse xlink:href='%23a' transform='rotate(45.87 1.273 16.18)'/%3e%3cuse xlink:href='%23a' transform='rotate(69.945 .996 12.078)'/%3e%3cuse xlink:href='%23a' transform='rotate(20.66 -19.689 31.932)'/%3e%3c/svg%3e)
