Tottori University Hospital

Vault RNA1-1 (vtRNA1-1) exhibits antiviral and anti-apoptotic effects in infected and malignant cells.We observed that vtRNA1-1 levels in serum fluctuate in patients with hematol. disorders, but its extracellular functions remain unclear.This study evaluates the potential of serum vtRNA1-1 levels as a biomarker for hematol. disorders and investigates its association with bone marrow cell d. (BMC).Blood and serum samples were collected from patients with hematol. disorders, patients who underwent bone marrow examination, PBSCT donors, and AML patients who received chemotherapy.VtRNA1-1 levels were measured using real-time quant. RT-PCR.BMC was calculated by digital image anal., and multiple regression anal. was performed using serum vtRNA1-1 and hematol. and biochem. data as explanatory variables.The vtRNA1-1 levels in the blood of 11 patients with hematol. disorders averaged 10.8 log₁₀ cps/mL, significantly higher than 8.4 log₁₀ cps/mL in serum.Multiple regression anal. estimated the vtRNA1-1 expression levels of each blood cell.In 87 patients who underwent bone marrow examination, there was a significant correlation between serum vtRNA1-1 levels and BMC (Rs = 0.24, P = 0.023).In PBSCT donors, serum vtRNA1-1 levels increased after G-CSF administration (P < 0.001), and in AML patients, serum vtRNA1-1 levels decreased after the initiation of chemotherapy, fluctuating in parallel with white blood cell counts.Our findings suggest that serum vtRNA1-1, derived from peripheral blood and bone marrow cells, can potentially serve as a clin. biomarker in specific diseases.

Extremely low uric acid (UA) levels or increased urinary UA (Uua) excretion might be risk factors for kidney disease in renal hypouricemia (RHU) patients, but their relationship with kidney dysfunction is unclear. This study investigated time-dependent changes in eGFR in RHU patients.

This multicenter retrospective study assessed UA metabolism and changes in eGFR (median 5.5 years) in 13 RHU patients. We then compared eGFR change in 7 of 13 RHU patients whose eGFR could be measured for 4 years with those in normouricemic group (n = 31). In addition, 7 RHU patients were divided into two groups based on URAT1 gene mutations: homozygote and compound heterozygote mutations (Homo/Com group, n = 3), and wild-type and heterogeneous mutations (WT/Hetero group, n = 4).

In 13 RHU patients, the median and mean serum UA (SUA) were 0.8 (0.4–2.5) and 1.1 ± 0.7 mg/dL. The median and mean Uua were 44.3 (12.7–141.1) and 49.7 ± 36.2 mg/dL. The median and mean urinary urate clearance (Cua/Ccr) were 46.8 (11.3–73.6) and 43.3 ± 19.7%. Over 4 years, eGFR did not change in the RHU group but declined in the normouricemic group. Annual mean eGFR decline and change rate in the RHU group were the same as those in the normouricemic group (− 1.09 ± 1.11 vs. − 1.09 ± 1.92 mL/min/1.73 m2/year, p = 0.996) (− 1.74 ± 1.96 vs. − 1.36 ± 2.10%, p = 0.664). And no significant difference was found in eGFR decline or change rate between Homo/Com and WT/Hetero groups (− 0.33 ± 1.03 vs. − 1.67 ± 0.85 mL/min/1.73 m2/year, p = 0.116) (− 0.61 ± 1.62 vs. − 2.59 ± 1.91%, p = 0.210).

RHU from URAT1 genetic mutation may not show eGFR decline over 4 consecutive years.

To evaluate the effects of a P2X4 receptor (P2X4R)-specific antagonist on murine endometriotic-like lesions and human endometriotic stromal cells.

Experimental study using an in vivo mouse endometriosis model and in vitro primary culture of human endometriotic stromal cells. NC-2600, an antagonist of the P2X4 ionotropic ATP receptor (P2X4R), was orally administered to the mice and cells. Gene expression analyses for cytokines were conducted in the endometriotic-like cysts and vaginal portion of mice, and immunohistochemistry was performed to evaluate the proliferative activity and localization of macrophages in addition to cytokine expression. The sensation of murine vaginal pain was evaluated using visceromotor responses.

NC-2600 reduced the proliferation of the cyst epithelium and vaginal pain sensation. In both cysts and vaginas, P2X4R is mainly expressed in macrophages, and NC-2600 reduces the number of tissue macrophages and reverses the elevated expression of InterleukinL-33 and cyclooxygenase-2 in animals with endometriosis.

These results indicate unknown pathophysiological roles of P2X4R expressed in local macrophages at the injury site of endometriosis and in the vagina, suggesting the potential therapeutic effects of orally administered P2X4R inhibitors for alleviating the symptoms of endometriosis.