RNA therapeutics for diarrhea.

Diarrhea is caused by a variety of bacterial and viral agents, inflammatory conditions, medications, and hereditary conditions. Secretory diarrhea involves several ion and solute transporters, activation of the cyclic nucleotide and Ca2+ signaling pathways, as well as intestinal epithelial secretion. In many cases of secretory diarrhea, activation of Cl- channels, such as the cystic transmembrane conduction regulator and the Ca2+stimulated Cl- channel fibrosis, promote secretion while concurrently inhibiting Na+ transport expressing fluid absorption. Current diarrhea therapies include rehydration and electrolyte replacement via oral rehydration solutions, as well as medications that target peristalsis or fluid secretion. The rising understanding of RNA function and its importance in illness has encouraged the use of various RNAs to operate selectively on "untreatable" proteins, transcripts, and genes. Some RNA-based medications have received clinical approval, while others are currently in research or preclinical studies. Despite major obstacles in the development of RNA-based therapies, many approaches have been investigated to improve intracellular RNA trafficking and metabolic stability.

Evaluation of the safety and immune stimulatory effects of multi-strain Lab Mix product on laboratory animals.

Background & aims: Probiotics are alive and beneficial bacteria used as food complements with sufficient amounts to improve and balance the intestinal flora in the human gastrointestinal tract and inhibit harmful microorganisms. In this study, we conducted experiments to evaluate he safety and the effect of one of our probiotics on selected biochemical parameters in animal models. Methods: LabMix is a probiotic product containing three bacterial strains, including Lactobacillus acidophilus LA 304.17, Lactobacillus casei LC 304.08, and Bifidobacterium bifidum BF 304.98, with a density of 9 × 109 CFU/g and being mixed with suitable excipients. In this study, we conducted experiments to evaluate LabMix's acute ttoxicity in mice as well as subchronic toxicity in rats. Results: The LD50 dose in mice of this product could not be determined since no death or disorder was recorded. In rats receiving LabMix with doses of 2.52 × 109 CFU/kg and 12.6 × 109 CFU/kg continuously for 28 days, this product caused no significant changes in the amount of red and white blood cells and platelets. Similarly, no significant changes were recorded in serum concentrations of hemoglobin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), glucose, protein, cholesterol, bilirubin, and creatinine. Besides, LabMix products also did not cause any changes in the histology of the liver, kidney, and spleen in rats. Moreover, LabMix was well tolerated without affecting the normal growth and feeding of rats. Furthermore, LabMix also decreased serum cytokines and increased serum and gut mucosal IgA antibodies. Conclusions: LabMix product is possibly considered safe for human., and this sproduct reduced the release of pro-inflammatory cytokines (IL-6 and TNF-α), but increased IgA levels. However, it is necessary to further evaluate the product's effectiveness in the preclinical phase as well as in further phases before mass production and commercialization.