Transcriptome analysis of genes and pathways associated with salt tolerance in alfalfa under non-uniform salt stress.

Soil salinity of fields is often non-uniform. To obtain a better understanding of molecular response to non-uniform salt stress, we conducted transcriptomic analysis on the leaves and roots of alfalfa grown under 0/0, 200/200, and 0/200 mM NaCl treatments. A total of 233,742 unigenes were obtained from the assembled cDNA libraries. There were 98 and 710 unigenes identified as significantly differentially expressed genes (DEGs) in the leaves of non-uniform and uniform salt treatment, respectively. Furthermore, there were 5178 DEGs in the roots under uniform salt stress, 273 DEGs in the non-saline side and 4616 in the high-saline side roots under non-uniform salt stress. Alfalfa treated with non-uniform salinity had greater dry weight and less salt damage compared to treatment with uniform salinity. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of the DEGs in roots revealed that both sides of the non-uniform salinity were enriched in pathways related to "phenylpropanoid biosynthesis" and "linoleic acid metabolism"; and "MAPK signaling pathway-plant" was also indicated as a key pathway in the high-saline roots. We also combined a set of important salt-response genes and found that roots from the non-saline side developed more roots with increased water uptake by altering the expression of aquaporins and genes related to growth regulation. Moreover, the hormone signal transduction and the antioxidant pathway probably play important roles in inducing more salt-related genes and increasing resistance to non-uniform salt stress on both sides of the roots.

The HRH4 rs11662595 mutation is associated with histamine H4 receptor dysfunction and with increased epithelial-to-mesenchymal transition progress in non-small cell lung cancer.

We previously demonstrated that histamine H4 receptor (HRH4) played important roles to suppress epithelial-to-mesenchymal transition (EMT) progress in non-small cell lung cancer (NSCLC). Furthermore, recent investigations suggested that genetic variations in HRH4 gene affected HRH4 function and eventually contributed to certain HRH4-related diseases. However, the relations between polymorphisms in HRH4 gene and NSCLC as well as their underlying mechanisms remain largely uninvestigated. This study aims to investigate the genetic effect of a nonsynonymous HRH4 polymorphism (rs11662595) on HRH4 function and its association with NSCLC both basically and clinically. For basic experiments, A549 cells were transfected with either wild type or rs11662595 mutated HRH4 clone and subjected to both in vitro and in vivo experiments. We showed that rs11662595 significantly decreased the ability of HRH4 to activate Gi protein, which resulted in facilitation of EMT progress, cell proliferation, and invasion behavior in vitro. Moreover, in vivo experiments also showed that rs11662595 attenuated the anti-EMT effects of HRH4 agonist in inoculated nu/nu mice. For clinical experiments, we performed a prospective cohort study among 624 NSCLC patients and further proved that rs11662595 was responsible for the prognosis, degree of malignancy and metastasis of NSCLC. In conclusion, these findings reveal that rs11662595 is a loss-of-function polymorphism that results in dysfunction of HRH4 and attenuates the anti-EMT function of HRH4 in NSCLC, which provides a promising biomarker for prognosis and therapy of NSCLC.

Retrospective Analysis of Vancomycin Nephrotoxicity in Elderly Chinese Patients.

This study explored nephrotoxicity in elderly Chinese patients after exposure to vancomycin and other nephrotoxic risk factors. This was a single-center retrospective study. The patient population included those who were ≥60 years of age, had normal baseline serum creatinine values, and received vancomycin for ≥48 h between January 1, 2013 and August 30, 2014. Nephrotoxicity occurred in 29% of 124 patients. A baseline creatinine clearance ≥63.5 ml/min was more common in the nephrotoxic group. Patients with high (≥15 mg/l) rather than low (<15 mg/l) average vancomycin troughs had elevated nephrotoxicity (47.2 vs. 27.3%, p = 0.0001). Of the comorbid conditions evaluated, there were more patients with shock (p = 0.001), hypertension (p = 0.020) and congestive heart failure (p = 0.04) in the nephrotoxic group. Drugs frequently given at the same time with vancomycin, such as angiotensin receptor blockers and furosemide, were also associated with increased nephrotoxic risk. In conclusion, nephrotoxicity was frequently observed in patients with concurrent vancomycin trough concentrations ≥15 µg/ml and hypertension, shock, congestive heart failure. In addition, drugs concurrently used with vancomycin may also increase its nephrotoxicity. Therefore, renal function and vancomycin serum troughs should be closely monitored, especially in patients with other renal injury risk factors.