ABSTRACT
Germline-encoded pattern recognition receptors [PRRs] in mammalian cells function in the detection of molecular patterns associated with pathogen invasion or cellular damage. A PRR subset is activated by the atypical presence and location of double-stranded RNA [dsRNA] or its synthetic analogue polyinosinic-polycytidylic acid [poly(I:C)], triggering pro-inflammatory signalling and death in many cell types. Poly(I:C) has been tested as a sole or combination cancer therapy in preclinical studies and clinical trials. The purpose of this study was to evaluate the effects of poly(I:C) transfection via electroporation on cell lines from a cancer of epithelial origin, 4T1 mammary carcinoma, and a cancer of mesenchymal origin, WEHI 164 fibrosarcoma. The effects of the poly(I:C) delivery on cell metabolism implicate the induction of cell death. A pro-inflammatory response was demonstrated by mRNA upregulation and the secretion of Type I interferon and several cytokines and chemokines. The mRNAs of dsRNA sensor DExD/H-box helicase 58/retinoic acid-inducible gene I protein [Ddx58/RIG-I] and sensor/co-sensor DEAH-box helicase 9 [Dhx9] were not regulated, but the mRNAs of RNA sensors toll-like receptor 3 [TLR3], interferon-induced with helicase C domain 1/melanoma differentiation-associated protein 5 [Ifih1/MDA5] and Z-DNA binding protein 1 [Zbp1] and co-sensors DEAD (Asp-Glu-Ala-Asp) box polypeptide 60 [Ddx60] and interferon-inducible protein 204 [Ifi204] were upregulated in both cell lines. The mRNAs encoding signalling pathways components were present or upregulated in both cell types. These data demonstrate that RNA sensing effects can be amplified by electroporation delivery, potentially expanding the practicality of this immunotherapeutic approach.
Subject(s)
Carcinoma , Fibrosarcoma , Interferon Type I , Animals , DEAD Box Protein 58/metabolism , DEAD-box RNA Helicases/genetics , DEAD-box RNA Helicases/metabolism , Fibrosarcoma/genetics , Interferon Type I/genetics , Mammals/genetics , Mice , Poly I-C/pharmacology , RNA, Double-Stranded/genetics , RNA, Messenger/genetics , RNA-Binding Proteins/metabolism , TransfectionABSTRACT
The likelihood ratio test, the large-sample z-test, and the large-sample z-test have been proposed to test for the equality of two intraclass correlation coefficients under unequal family sizes based on two independent multinomial samples. It has been found on the basis of simulation studies that the likelihood ratio test consistently and reliably produces results superior to those of the large-sample z-test and large-sample z-test in terms of power for various combinations of intraclass correlation coefficient values.
Subject(s)
Biometry/methods , Family Characteristics , Computer Simulation , Female , Humans , Likelihood Functions , MaleABSTRACT
A total of 98 medicinal preparations, involving 69 species of plants, used by the Siddis of Uttara Kannada in the state of Karnataka is described in this paper based on an ethnomedical field study. The finding includes 40 hitherto unknown medicinal uses of known medicinal plants. Among these, the use of the stem sap of Calamus thwaitesii as an antifertility drug, and the use of the flowers of Ichnocarpus frutescens and the rhizome of Hedychium coronarium in the treatment of diabetes are noteworthy. The knowledge of medicinal plants of the Siddis is distinct from that of another tribe of the same locality, the Gowlis.
