Jumu is required for the activation of JAK/STAT in Drosophila lymph gland development and epidermal wounds.

The regulatory mechanism of hematopoiesis and innate immunity in Drosophila is highly similar to that in mammals, and Drosophila has become a suitable model to understand vertebrate hematopoiesis and the immune response. JAK-STAT signaling pathway components are widely conserved during evolution, and contribute to hematopoiesis and multiple tissue damage and immune responses. Here, we demonstrate that Stat92E is widely expressed in the lymph gland, and the loss of jumu inhibits the maintenance of the JAK/STAT pathway in the CZ and MZ but not in the PSC of the lymph gland. Furthermore, we found that clean puncture wounding of the larval epidermis can lead to the activation of JAK/STAT signaling and the generation of lamellocytes, and Jumu is required for the activation of JAK/STAT in response to epidermal wounds.

Vitamin K1 Inhibition of Renal Crystal Formation through Matrix Gla Protein in the Kidney.

BACKGROUND AND OBJECTIVES: Vitamin K (VK) plays a major role in modifying the binding of calcium in bones and blood vessels. Understanding the effect of VK on crystal formation in the kidney would contribute to advancing the treatment and prevention of kidney stones. METHODS: Rats were treated with vitamin K1 (VK1) for 8 weeks. VK1 levels were detected and crystal formation were observed. HK2 cells were exposed to calcium oxalate monohydrate crystals. Apoptosis and cell viability were detected. Crystal deposition was analyzed using atomic absorption assay. The adenovirus vectors expressing matrix Gla protein (MGP) and siMGP were constructed to elucidate the effect and mechanism of VK1 on crystal formation. MGP expression in vivo and in vitro was analyzed by Western blot. The mRNA levels of monocyte chemoattractant protein-1 (MCP-1) and collagen I was measured by semiquantitative RT-PCR. RESULTS: The concentrations of VK1 in whole blood and kidney tissues rose under treatment with VK1. Crystal formation was inhibited from the second to the 6th week, the frequency and quality of crystal formation decreased significantly, and the location of crystal formation was limited to a greater extent in the rats treated by VK1 compared to the control group. Warfarin treatment in the crystals-exposed HK2 cells significantly increased the number of crystals adhering to cells and the number of apoptotic cells and reduced cell viability. VK1 treatment reversed warfarin's above influence. VK1 inhibited the upregulations of MCP-1 and collagen I in kidney tissues under crystal load. VK1 treatment increased MGP expression in vivo and in vitro, and MGP is necessary for VK1 to play a role in crystal deposition in cells. CONCLUSIONS: VK1 treatment can inhibit the formation of renal crystals in vivo. VK1 increases MGP expression and functions through MGP to reduce crystal deposition in cells and provide cell protection. Our findings suggest that VK1 treatment could be a potential strategy for the treatment and prevention of nephrolithiasis.

In Silico Screening and Molecular Dynamic Study of Nonsynonymous Single Nucleotide Polymorphisms Associated with Kidney Stones in the SLC26A6 Gene.

PURPOSE: SLC26A6 is a multifunctional anion transporter with a critical physiological role in the transport of oxalate anions. Recognizing a genetic variant of SLC26A6 would advance our understanding of oxalate transport in the formation of calcium oxalate stones. MATERIALS AND METHODS: All nsSNPs (nonsynonymous single nucleotide polymorphisms) reported in human SLC26A6 were investigated using 4 in silico tools, including SIFT (Sorting Intolerant From Tolerant), PROVEAN (Protein Variation Effect Analyzer), PhD-SNP (Predictor of human Deleterious Single Nucleotide Polymorphisms) and MutPred. A total of 426 subjects, including 225 with kidney stones and 201 healthy controls, were included in study to genotype the candidate disease associated nsSNP using allele specific polymerase chain reaction. Furthermore, the structural consequences due to the mutation were assessed using homology modeling and molecular dynamics simulation methods. RESULTS: The nsSNP rs184187143 was identified as a more probable disease associated variant in the SLC26A6 gene by in silico screening. The C allele carrier showed a 6.1-fold increased kidney stone risk compared with G allele carriers in the nsSNP (OR 6.1, 95% CI 1.36-27.38, p = 0.007). We found that the mutation from arginine to glycine leads to the loss of 2 hydrogen bonds and to an unstable structure in the STAS domain of SLC26A6. CONCLUSIONS: Our results indicate that the variant G539R in the SLC26A6 gene is associated with kidney stone risk, providing a clear clue to further achieve insight into oxalate transport in kidney stone formation.

Effects of small molecules water that may retard kidney stone formation.

PURPOSE: Water intake is important for preventing kidney stones. Small molecules water is a more active restructured water under magnetic field. Here, we studied the relation between small molecules water and crystal formation in the rat kidney. MATERIALS: The small molecules water was prepared by a water machine providing a 0.8-T magnetic field. Calcium oxalate crystals were induced by 0.75% EG (ethylene glycol) in male Sprague-Dawley rats by drinking small molecules water and plain water for up to 6 weeks, respectively. Urinary ions were assayed. Osteopontin mRNA expression and urinary LDH were detected. Crystals were observed using a light microscope and a polarizing microscope. RESULTS: A significantly reduced urinary calcium and phosphorus excretion occurred in the 2nd and the 4th week after treatment of small molecules water. Crystals were initially detected in 40% of the experimental rats in the small molecules water group at the 6th week, later than the control group in which crystals were detected in 60% of rats at the 4th week. After 6 weeks of treatment, crystals were observed to form in renal cortex, medulla and papilla in the control group, whereas only to form in renal medulla and papilla in the small molecules water group. OPN mRNA expression significantly increased earlier in the 2nd week after treatment of the small molecules water compared to the control (P = 0.016). CONCLUSIONS: Small molecules water may retard crystal formation, reduce urinary calcium and phosphorus excretion and promote earlier OPN mRNA expression in the rat kidney.

Rgn gene is required for gut cell homeostasis after ingestion of sodium dodecyl sulfate in Drosophila.

Resistance and resilience constitute the two complementary aspects of epithelial host defenses in Drosophila. Epithelial cell homeostasis is necessary for the recovery of damages caused by stress or infections. However, the genes responsible for gut epithelial homeostasis remain poorly understood. Here, we show that rgn(G4035) mutant flies have higher mortality than wild-type flies after ingestion of sodium dodecyl sulfate (SDS). Excessive melanization and increased necrotic cells in the gut contribute to the reduced survival of rgn(G4035) mutant flies following SDS ingestion. rgn mutant flies have a defect in the replenishment of intestinal stem cells (ISCs) following gut damage. The antimicrobial peptide (AMP) expression is affected in rgn(G4035) mutant fly guts. Together, our study provides evidence that rgn gene is essential for gut cell homeostasis following damage in Drosophila.