P., R. | bioRxiv Science

bioRxiv2024

In-silico analysis of important mitochondrial microRNAs and their differential expression in mitochondria

Mitochondria, often called as the power house of cell, serves important role in cellular physiology and survivability. It plays crucial role in the normal functioning of the cell. Dysfunctional mitochondria have been found to be associated with various pathological conditions including cancer. The modulation of mitochondrial machinery could be due to the suppression of the expression pattern of important mitochondrial genes and microRNAs could be considered as the key player in reprograming of the mitochondrial metabolism. Apart from the microRNAs coded by mitochondrial genome, nuclear coded microRNAs gets localized to the mitochondria and they influence the mitochondrial machinery by targeting the important mitochondrial genes. This group of microRNAs are called mitochondrial miRNAs or MitomiRs. In this study we selected 10 important candidate mitochondrial microRNAs and checked their abundance in the cancerous and non cancerous hepatic cell line (HepG2 and WRL68), followed by their differential expression in the mitochondria of the respective cell line. The results shown an inverse relation in the expression pattern of the candidate microRNAs with mitochondrial target genes, suggesting their direct targeting, as predicted by our in-silico data.

cancer biology↗

bioRxiv2021

Experimental safety testing shows that the NSAID tolfenamic acid is not toxic to Gyps vultures in India at concentrations likely to be encountered in cattle carcasses

Population declines of Gyps vultures across the Indian subcontinent were caused by unintentional poisoning by the non-steroidal anti-inflammatory drug (NSAID) diclofenac. Subsequently, a number of other NSAIDs have been identified as toxic to vultures, while one, meloxicam, is safe at concentrations likely to be encountered by vultures in the wild. Other vulture-safe drugs need to be identified to reduce the use of those toxic to vultures. We report on safety-testing experiments on the NSAID tolfenamic acid on captive vultures of three Gyps species, all of which are susceptible to diclofenac poisoning. Firstly, we estimated the maximum level of exposure (MLE) of wild vultures and gave this dose to 38 Near Threatened G. himalayensis by oral gavage, with 15 control birds dosed with benzyl alcohol (the carrier solution for tolfenamic acid). Two birds given tolfenamic acid died with elevated uric acid levels and severe visceral gout, while the remainder showed no adverse clinical or biochemical signs. Secondly, four G. himalayensis were fed tissues from water buffaloes which had been treated with double the recommended veterinary dose of tolfenamic acid prior to death and compared to two birds fed uncontaminated tissue; none suffered any clinical effects. Finally, two captive Critically Endangered vultures, one G. bengalensis and one G. Indicus, were given the MLE dose by gavage and compared to two control birds; again, none suffered any clinical effects. The death of two G. himalayensis may have been an anomaly due to i) the high dose level used and ii) the high ambient temperatures at the time of the experiment. Tolfenamic acid is likely to be safe to Gyps vultures at concentrations encountered by wild birds and could therefore be promoted as a safe alternative to toxic NSAIDs. It is manufactured in the region, and is increasingly being used to treat livestock.

pharmacology and toxicology↗