Double stranded RNA is generated during viral replication. The synthetic analogue poly I:C is frequently used to mimic anti-viral innate immune responses in models of psychiatric and neurodegenerative disorders including schizophrenia, autism, Parkinson's disease and Alzheimer's disease. Many studies perform limited analysis of innate immunity despite these responses potentially differing as a function of dsRNA molecular weight and age. Therefore fundamental questions relevant to impacts of systemic viral infection on brain function and integrity remain. Here, we studied innate immune-inducing properties of poly I:C preparations of different lengths and responses in adult and aged mice. High molecular weight (HMW) poly I:C (1-6 kb, 12 mg/kg) produced more robust sickness behavior and more robust IL-6, IFN-I and TNF-α responses than poly I:C of < 500 bases (low MW) preparations. This was partly overcome with higher doses of LMW (up to 80 mg/kg), but neither circulating IFNβ nor brain transcription of Irf7 were significantly induced by LMW poly I:C, despite brain Ifnb transcription, suggesting that brain IFN-dependent gene expression is predominantly triggered by circulating IFNβ binding of IFNAR1. In aged animals, poly I:C induced exaggerated IL-6, IL-1β and IFN-I in the plasma and similar exaggerated brain cytokine responses. This was associated with acute working memory deficits selectively in aged mice. Thus, we demonstrate dsRNA length-, IFNAR1-and age-dependent effects on anti-viral inflammation and cognitive function. The data have implications for CNS symptoms of acute systemic viral infection such as those with SARS-CoV-2 and for models of maternal immune activation.
Double stranded RNA is generated during viral replication. The synthetic analogue poly I:C is frequently used to mimic anti-viral innate immune responses in models of psychiatric and neurodegenerative disorders including schizophrenia, autism, Parkinson’s disease and Alzheimer’s disease. Many studies perform limited analysis of innate immunity despite these responses potentially differing as a function of dsRNA molecular weight and age. Therefore fundamental questions relevant to impacts of systemic viral infection on brain function and integrity remain. Here, we studied innate immune-inducing properties of poly I:C preparations of different lengths and responses in adult and aged mice. High molecular weight (HMW) poly I:C (1-6kb, 12 mg/kg) produced more robust sickness behavior and more robust IL-6, IFN-I and TNFα responses than poly I:C of <500 bases (low MW) preparations. This was partly overcome with higher doses of LMW (up to 80 mg/kg), but neither circulating IFNβ nor brain transcription of Irf7 were significantly induced by LMW poly I:C, despite brain Ifnb transcription, suggesting that brain IFN-dependent gene expression is predominantly triggered by circulating IFNβ binding of IFNAR1. In aged animals, poly I:C induced exaggerated IL-6, IL-1β and IFN-I in the plasma and similar exaggerated brain cytokine responses. This was associated with acute working memory deficits selectively in aged mice. Thus, we demonstrate dsRNA length-, IFNAR1- and age-dependent effects on anti-viral inflammation and cognitive function. The data have implications for CNS symptoms of acute systemic viral infection such as those with SARS-CoV-2 and for models of maternal immune activation.
Herbal curd was prepared by adding the Gymnema sylvestre leaf extract during fermentation and its activity against liver cancer was investigated on HepG2 cell lines by MTT (3‐[4,5‐dimethylthiazole‐2yl]‐2,5‐diphenyltetrazolium bromide) assay. The prepared herbal curd was characterized with the help of qualitative phytochemical analysis, Fourier transform infrared (FT‐IR) spectroscopy and gas chromatography‐ mass spectrometry (GC–MS). The sensory attributes and stability of the herbal curd were also determined. The qualitative phytochemical analysis of the herbal curd showed the transfer of phenolic compounds from the plant extract to herbal curd. The FT‐IR analysis exhibited that the Anhydride group present in the plant extract was infused into the herbal curd in addition to its other functional groups such as Alcohol, Alkyne, Alkene, Amide, Sulfate, Ether and Esters. The GC–MS analysis revealed the presence of 10 new compounds which were not present in curd or plant extract. The results of MTT assay showed that the herbal curd had significantly reduced the growth of HepG2 cells. The sensory evaluation proved that the herbal curd was delicious than the plant extract. Hence, it can be used as a potential food supplement for the treatment of liver cancer. Practical Applications Fermented milk products have been used for the prevention and treatment of various diseases including cancer and diabetes. Recently, the usage of medicinal plants for the treatment of cancer and other diseases has gained incredible attention due to their higher activity and minimal side effects. Gymnema sylvestre is a pharmacologically significant medicinal plant, used in different kinds of poly‐herbal formulations for the treatment of various diseases. In the present study, it was used for the preparation of herbal curd that will serve as an alternative remedial measure for treating liver cancer.
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