Low-Intensity Ultrasound as a Novel Strategy to Improve the Cytotoxic Effect of Oncolytic Reovirus on Colorectal Cancer Model Cells.

BACKGROUND: Colorectal cancer is the third most common cancer all over the world, so in the battle to fight this hurdle, new therapeutic approaches such as oncolytic viruses (OV) have attracted much attention because of the fact that they can inherently kill cancer cells. Oncolytic reovirus is one of the candidates for treatment as a nonpathogenic species specially reovirus type 3 Dearing (T3D), which can induce apoptosis. To speed up the entry and function of the reovirus, low-intensity ultrasound, which is a safe system for damage to the cells and tissues, is a promising approach to be used in combination with other therapeutic approach. METHODS: L929 and CT26 cells were infected with reovirus T3D and were exposed to ultrasonic irradiation (1 MHz, 1 W/cm2, and 20% duty factor) for 10 s. The viruses' titer level of both groups was calculated in 2 types of cells by using the CCID50 method and compared with each other. Apoptosis, after 24 h, was measured by the flow cytometry method. RESULT: The results of CCID50 in infected cells were exposed to low-intensity ultrasound showed an increased virus titer compared with unexposed infected cells. Moreover, according to the results of the flow cytometry test, it was found that the amount of apoptosis in infected cells that are exposed to low-intensity ultrasound waves is higher than those infected cells. CONCLUSION: Due to the results of CCID50 and flow cytometry tests, low-intensity ultrasound increases the cytotoxicity level of reovirus in CT26 cells of the cellular colorectal cancer model.

The reovirus variant RP116 is oncolytic in immunocompetent models and generates reduced neutralizing antibodies to Type 3 Dearing.

The mammalian reovirus Type 3 Dearing (T3D) is a naturally occurring oncolytic virus. We previously identified a T3D variant isolated from persistently infected cancer cells that has a premature stop codon mutation in the S1 gene, generating a truncated σ1-attachment protein that lacks the globular head. We now report on the molecular characterization of this variant, named RP116, and assess its antitumor potential in human cancer cells and syngeneic mouse models. RP116 replicates efficiently in several cancer cell lines, shows reduced dependency for the JAM-A receptor, significantly decreases tumor growth in syngeneic models when injected either intratumorally or intravenously, and generates long-term cures and immune memory in combination with checkpoint inhibitors. Finally, we demonstrate that RP116 infection in mice leads to reduced production of neutralizing antibodies directed against reovirus T3D, preserving the efficacy of subsequent reovirus treatment. These results establish the value of developing RP116 as an additional oncolytic reovirus platform.

Shear bioreactors stimulating chondrocyte regeneration, a systematic review.

It is commonly accepted that the mechanical stimuli are important factors in the maintenance of normal structure and function of the articular cartilage. Despite extensive efforts, the cellular mechanisms underlying the responses of articular chondrocytes to mechanical stresses are not well understood. In the present review, different types of shear bioreactor and potential mechanisms that mediate and regulate the effect of shear on chondrocyte are discussed. For this review, the search of the literature was done in the PubMed, Scopus, Web of sciences databases to identify papers reporting data about shear on chondrocyte. Keywords "shear, chondrocyte, cartilage, bioreactor" were used. Studies published until the first of March 2018 were considered in this paper. The review focused on the experimental studies conducted the effect of shear stress on cartilage tissue in vivo and in vitro. In this review, both experimental studies referring to human and animal tissues were taken into account. The following articles were excluded: reviews, meta-analysis, duplicate records, letters, and papers that did not add significant information. Mechanism of shear stress on chondrocyte, briefly can be hypothesized as (1) altered expression of aggrecan and collagen type II, (2) altered cartilage oligomeric matrix protein (COMP) serum levels, consequently, organizing the arrangement binding of glycosaminoglycans, integrins, and collagen, (3) induction of apoptosis signals, (4) altered expression of integrin.

Fifteen new species of Liphanthus Reed (Hymenoptera: Andrenidae) with two submarginal cells.

Hitherto, the panurgine genus Liphanthus Reed 1894 has been thought to have only a single species with two, as opposed to three, submarginal cells. Here we describe an additional fifteen species with two submarginal cells. These new species are: L. jenamro Mir Sharifi Packer, L. sapos Mir Sharifi Packer, L. domeykoi Packer, L. discolor Mir Sharifi Packer, L. centralis Mir Sharifi Packer, L. molavi Mir Sharifi Packer (all of the above are from Chile), L. abotorabi Mir Sharifi Packer, L. cochabambensis Mir Sharifi Packer (both from Bolivia), L. fritzi Mir Sharifi Packer, L. amblayensis Mir Sharifi Packer (both from Argentina), L. ancashensis Mir Sharifi Packer (from Peru), L. tregualemensis Packer (from Chile), L. yrigoyeni Packer, L. sparsipunctus Packer (both from Argentina) and L. aliavenus Packer (from Chile). Only L. tregualemensis readily fits within any of the previously described subgenera-Liphanthus (Leptophanthus) Ruz and Toro 1983. Liphanthus aliavenus is known from two specimens, one with three and one with two submarginal cells whereas L. molavi has one individual with two submarginal cells on one forewing and three on the other while all other specimens have two submarginal cells on each forewing. We verified that none of these new species are merely two submarginal celled variants of species with three submarginal cells (such intraspecific variation arises also in some other bees) by i) comparing each of the new species with all keys, figures and descriptions of all Liphanthus species, ii) comparisons with holotypes and/or paratypes of most of the described species and iii) surveys of the specimens of undescribed species with three submarginal cells in our collection. None of the new species seem closely related to L. (Neoliphanthis) bicellularis Ruz and Toro 1983, the only previously described Liphanthus species with two submarginal cells. It is the second submarginal crossvein that is lost in all species except L. aliavenus in which the first submarginal cross vein is lost. DNA barcode data are presented for some of the species. Some interesting morphological features associated with the penis valves are described and discussed. The genus is recorded from Bolivia for the first time.