Xerostomia is a state of oral dryness associated with salivary gland dysfunction and is induced by stress, radiation and chemical therapy, various systemic and autoimmune diseases, and specific medications. Fluid secretion is interrupted by the stimulation of neurotransmitter-induced increase in cytosolic calcium ([Ca]) in salivary gland acinar cells, prompting the mobilization of ion channels and their transporters. Salivary fluid and protein secretion are principally dependent on parasympathetic and sympathetic nerves. Various inflammatory cytokines allied with lymphocytic infiltration cause glandular damage and Sjogren's syndrome, an autoimmune exocrinopathy associated with hyposalivation. A defect in IPRs, a major calcium release channel, prompts inadequate agonist-induced [Ca] in acinar cells and deters salivary flow. The store-operated calcium entry-mediated Ca movement into the acini activates K and Cl channels, which further opens a water channel protein, aquaporin-5, and triggers the release of fluid secretion from the salivary glands. The cellular mechanism of salivary gland dysfunction and hyposalivation has not yet been elucidated. In this review, we focused mainly on the proteins responsible for deficient saliva, the correlation between inflammation and salivation, autoimmune disorders and other ailments or complications associated with hyposalivation.

P128 is an anti-staphylococcal protein consisting of the Staphylococcus aureus phage-K-derived tail-associated muralytic enzyme (TAME) catalytic domain (Lys16) fused with the cell-wall-binding SH3b domain of lysostaphin. In order to understand the mechanism of action and emergence of resistance to P128, we isolated mutants of Staphylococcus spp., including meticillin-resistant Staphylococcus aureus (MRSA), resistant to P128. In addition to P128, the mutants also showed resistance to Lys16, the catalytic domain of P128. The mutants showed loss of fitness as shown by reduced rate of growth in vitro. One of the mutants tested was found to show reduced virulence in animal models of S. aureus septicaemia suggesting loss of fitness in vivo as well. Analysis of the antibiotic sensitivity pattern showed that the mutants derived from MRSA strains had become sensitive to meticillin and other b-lactams. Interestingly, the mutant cells were resistant to the lytic action of phage K, although the phage was able to adsorb to these cells. Sequencing of the femA gene of three P128-resistant mutants showed either a truncation or deletion in femA, suggesting that improper cross-bridge formation in S. aureus could be causing resistance to P128. Using glutathione S-transferase (GST) fusion peptides as substrates it was found that both P128 and Lys16 were capable of cleaving a pentaglycine sequence, suggesting that P128 might be killing S. aureus by cleaving the pentaglycine cross-bridge of peptidoglycan. Moreover, peptides corresponding to the reported cross-bridge of Staphylococcus haemolyticus (GGSGG, AGSGG), which were not cleaved by lysostaphin, were cleaved efficiently by P128. This was also reflected in high sensitivity of S. haemolyticus to P128. This showed that in spite of sharing a common mechanism of action with lysostaphin, P128 has unique properties, which allow it to act on certain lysostaphin-resistant Staphylococcus strains.

Compromised protein folding capacity in the endoplasmic reticulum (ER) leads to a protein traffic jam that produces a toxic environment called ER stress. However, the ER smartly handles such a critical situation by activating a cascade of proteins responsible for sensing and responding to the noxious stimuli of accumulated proteins. The ER protein load is higher in secretory cells, such as liver hepatocytes, which are thus prone to stressmediated toxicity and various diseases, including alcohol-induced liver injury, fatty liver disease, and viral hepatitis. Therefore, we discuss the molecular cues that connect ER stress to hepatic diseases. Moreover, we review the literature on ER stress-regulated miRNA in the pathogenesis of liver diseases to give a comprehensive overview of mechanistic insights connecting ER stress and miRNA in the context of liver diseases. We also discuss currently discovered regulated IRE1 dependent decay in regulation of hepatic diseases.