Interferon regulatory factor 6 ( IRF6) acts as a tumor suppressor and controls cell differentiation in ectodermal and craniofacial tissues by regulating expression of target genes. Haploinsufficiency of IRF6 causes Van der Woude and popliteal pterygium syndrome, 2 syndromic forms of cleft lip and palate. Around 85% of patients with Van der Woude express pits on the lower lip that continuously or intermittently drain saliva, and patients with the common cleft lip and palate have a higher prevalence of dental caries and gingivitis. This study aims to identify the role of IRF6 in development of exocrine glands, specifically the major salivary glands. Our transgenic mouse model that expresses LacZ reporter under the control of the human IRF6 enhancer element showed high expression of IRF6 in major and minor salivary glands and ducts. Immunostaining data also confirmed the endogenous expression of IRF6 in the developing ductal, serous, and mucous acinar cells of salivary glands. As such, we hypothesized that Irf6 is important for proper development of salivary glands and potentially other exocrine glands. Loss of Irf6 in mice causes an increase in the proliferation level of salivary cells, disorganized branching morphogenesis, and a lack of differentiated mucous acinar cells in submandibular and sublingual glands. Expression and localization of the acinar differentiation marker MIST1 were altered in Irf6-null salivary gland and pancreas. The RNA-Seq analysis demonstrated that 168 genes are differentially expressed and confer functions associated with transmembrane transporter activity, spliceosome, and transcriptional regulation. Furthermore, expression of genes involved in the EGF pathway-that is, Ereg, Ltbp4, Matn1, Matn3, and Tpo-was decreased at embryonic day 14.5, while levels of apoptotic proteins were elevated at postnatal day 0. In conclusion, our data report a novel role of Irf6 in exocrine gland development and support a rationale for performing exocrine functional tests for patients with IRF6-damaging mutations.

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Chronic arsenicosis remains a condition of public health concerns in many countries of the world and has been linked to many other diseases. This condition has been managed in humans using a combination of therapy with differing outcomes. We conducted a controlled experiment to assess the effect of chronic arsenicosis on hematological and biochemical changes in Long-Evans rats and to assess the protective role of Spirulina combined with vitamin A following experimental arsenicosis, using daily oral doses of sodium arsenite for 63 days. The values of SGOT (Serum glutamate oxaloacetate transaminase) and SC (Serum creatinine) increased significantly (P<0.01) in all the treated groups of rats (T 1 , T 2 , T 3 and T 4 ) compared to the control (T 0 ) group, but Spirulina combined with Vitamin A produced values significantly comparable to the untreated control group. Whereas SGPT (Serum glutamate pyruvate transaminase) showed slight significance differences among the treatment groups, Spirulina combined with Vitamin A appeared most effective in managing arsenic treatment. Spirulina + Vitamin A increased the values of TEC, TLC and Hb (Total erythrocyte count, Total leukocyte count and Hemoglobin) against arsenic toxicity in rats but showed no significance differences. In conclusion, the combination of Spirulina and vitamin A were found more effective in the prevention of chronic arsenicosis in rat than using these substances (Spirulina or Vitamin A) alone.