The diagnostic accuracy of urinary neutrophil gelatinase-associated lipocalin in assessing kidney function in severe hydronephrosis.

Background: Up to now, there is no perfect indicator to evaluate the renal function of severe hydronephrosis, which poses difficulties in the selection of clinical treatment decisions. This study investigates the role of neutrophil gelatinase-associated lipocalin (NGAL) in urine drained from the nephrostomy tube shortly after nephrostomy to evaluate the renal function of patients with severe hydronephrosis caused by ureteral obstruction. Methods: The clinical data, and blood and urine samples of 24 patients with severe hydronephrosis due to ureteral obstruction were retrospectively collected. The NGAL in the urine drained from the nephrostomy tube on the morning of the first day after the procedure was measured. The glomerular filtration rate (GFR) was determined using a nuclear scan, and the clearance rate of creatinine was calculated based on nephrostomy drainage. The correlation between the NGAL level, urine volume post-nephrostomy, affected side GFR, and creatinine clearance rate (Ccr) was assessed. Moreover, the relationship between the urinary NGAL levels and prognosis was analyzed based on whether the patients underwent nephrectomy. Results: There was a significant correlation between the urine NGAL from the nephrostomy of the affected side and the Ccr and urine volume post-nephrostomy (both P<0.05). Compared with the patients in the kidney preservation group, those who underwent nephrectomy had significantly increased NGAL levels, and significantly reduced Ccrs and nephrostomy drainage urine output. Through the receiver operating characteristic (ROC) curve evaluation, the efficacy of NGAL in predicting nephrectomy was found to be superior to both the Ccr and urine output, with an area under the curve (AUC) of 0.845. Conclusions: The NGAL in the urine shortly after nephrostomy may indicate severe renal functional deterioration.

A Novel Quinazoline Derivative Prevents and Treats Arsenic-Induced Liver Injury by Regulating the Expression of RecQ Family Helicase.

Arsenic is a carcinogenic metalloid toxicant widely found in the natural environment. Acute or prolonged exposure to arsenic causes a series of damages to the organs, mainly the liver, such as hepatomegaly, liver fibrosis, cirrhosis, and even hepatocellular carcinoma. Therefore, it is imperative to seek drugs to prevent arsenic-induced liver injury. Quinazolines are a class of nitrogen heterocyclic compounds with biological and pharmacological effects in vivo and in vitro. This study was designed to investigate the ameliorating effects of quinazoline derivatives on arsenic-induced liver injury and its molecular mechanism. We investigated the mechanism of the quinazoline derivative KZL-047 in preventing and ameliorating arsenic-induced liver injury in vitro by cell cycle and apoptosis. We performed real-time fluorescence quantitative polymerase chain reaction (qPCR) and Western blotting combined with molecular docking. In vivo, the experiments were performed to investigate the mechanism of KZL-047 in preventing and ameliorating arsenic-induced liver injury using arsenic-infected mice. Physiological and biochemical indices of liver function in mouse serum were measured, histopathological changes in liver tissue were observed, and immunohistochemical staining was used to detect changes in the expression of RecQ-family helicases in mouse liver tissue. The results of in vitro experiments showed that sodium arsenite (SA) inhibited the proliferation of L-02 cells, induced apoptosis, blocked the cell cycle at the G1 phase, and decreased the expression of RecQ family helicase; after KZL-047 treatment in arsenic-induced L-02 cells, the expression of RecQ family helicase was upregulated, and the apoptosis rate was slowed, leading to the restoration of the cell viability level. KZL-047 inhibited arsenic-induced oxidative stress, alleviated oxidative damage and lipid peroxidation in vivo, and ameliorated arsenic toxicity-induced liver injury. KZL-047 restored the expression of RecQ family helicase proteins, which is consistent with the results of in vitro studies. In summary, KZL-047 can be considered a potential candidate for the treatment of arsenic-induced liver injury.

Schistosoma japonicum cystatin suppresses osteoclastogenesis via manipulating the NF­κB signaling pathway.

Abnormal osteoclastic activation and secretion of cysteine proteinases result in excessive bone resorption, which is one of the primary factors in the development of bone metabolic disorders, such as rheumatoid arthritis and osteoporosis. Mammalian cystatins have been demonstrated to restrain osteoclastic bone resorption and to alleviate severe osteolytic destruction via blocking the activity of cysteine proteinases. However, the specific effects of parasite cystatins on the formation and function of osteoclasts remain unclear. The purpose of the current study was to explore the effects of cystatins from Schistosoma japonicum (Sj­Cys) on macrophage colony­stimulating factor (M­CSF) and receptor activator of NF­κB ligand (RANKL)­induced osteoclast differentiation, as well as the underlying molecular mechanisms. Recombinant Sj­Cys (rSj­Cys) dose­dependently restrained osteoclast formation, with a half­maximal inhibitory concentration (IC50) value of 0.3 µM, and suppressed osteoclastic bone resorptive capability in vitro. The findings were based on tartrate resistant acid phosphatase (TRAP) staining and bone resorption assays, respectively. However, the cell viability assay showed that the repression of rSj­Cys on osteoclast formation did not depend on effects on cell viability or apoptosis. Based on the results of reverse transcription­quantitative PCR and western blot analysis, it was found that rSj­Cys downregulated the expression levels of osteoclastogenesis­related genes and proteins, by interfering with M­CSF and RANKL­induced NF­κB signaling and downstream transcription factors during early­phase osteoclastogenesis. Overall, the results of the present study revealed that rSj­Cys exerted an inhibitory role in osteoclast differentiation and could be a prospective biotherapeutic candidate for the treatment and prevention of bone metabolic disorders.