Diagnostic and prognostic values of KLK11 in nasopharyngeal carcinoma.

OBJECTIVE: This study aims to clarify potential diagnostic and prognostic values of KLK11 in nasopharyngeal carcinoma (NPC). PATIENTS AND METHODS: KLK11 levels in 81 primary NPC tissues, 24 recurrent NPC tissues, and 60 nasopharyngeal tissues with chronic mucosal inflammation were determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Then, receiver operating characteristic (ROC) curves were depicted for assessing the diagnostic value of KLK11 in primary and recurrent NPC. Next, correlation between KLK11 level and pathological indexes of NPC patients was analyzed by Chi-square test. Enrolled NPC patients were followed up for 5 years, and the follow-up data were recorded to determine the potential influence of KLK11 on overall survival by Kaplan-Meier method. In addition, Cox regression model was applied for assessing factors that could affect prognosis of NPC patients. RESULTS: It was found that KLK11 level was higher in primary NPC tissues than that in nasopharyngeal tissues with chronic mucosal inflammation. In recurrent NPC tissues, KLK11 was upregulated relative to primary ones. In addition, ROC curves revealed a certain diagnostic value of KLK11 in NPC. Overall survival was worse in primary and recurrent NPC patients expressing a high level of KLK11. By analyzing the pathological indexes of NPC patients, KLK11 level was found to be correlated with age, T stage, and clinical stage of NPC patients. Furthermore, KLK11 level was found to be the risk factor influencing the survival of NPC patients. CONCLUSIONS: KLK11 is upregulated in NPC tissues, and unfavorable to the prognosis of NPC. Besides, it can be utilized as a potential hallmark for diagnosing NPC.

Remifentanil protects neurological function of rats with cerebral ischemia-reperfusion injury via NR2B/CaMKIIα signaling pathway.

The effects of remifentanil were studied on cerebral ischemia-reperfusion injury (IRI) in rats, and its regulatory effect was explored on the N-methyl D-aspartate receptor subtype 2B (NR2B)/calcium/calmodulin-dependent protein kinase type II subunit alpha (CaMKII) signaling pathway in cerebral tissues. A total of 40 Sprague-Dawley rats were randomly assigned into sham group, model group, low-dose group (remifentanil injected into the caudal veins at 2 µg/kg) and high-dose group (remifentanil injected into the caudal veins at 10 µg/kg). Then, in the model, low-dose and high-dose groups, the rat model of cerebral IRI was established through middle cerebral artery occlusion (namely, ischemia for 1 h and reperfusion for 2 h), while no thread was inserted into the rats in the sham group. Neurological function of rats in each group was evaluated, and the cerebral infarct size was measured using 2,3,5-triphenyltetrazolium chloride (TTC) staining. Moreover, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining was performed to determine the neuronal apoptosis level, and mitochondrial membrane potential was measured via JC-1 assay. Moreover, the reactive oxygen species (ROS) level in neurons and the malondialdehyde (MDA) content in cerebral tissues were determined using 2',7'-dichlorofluorescin diacetate (DCFH-DA) assay and enzyme-linked immunosorbent assay (ELISA), respectively. Finally, the expression levels of apoptosis-associated proteins and the NR2B/CaMKIIα signaling pathway-associated proteins in cerebral tissues were measured by Western blotting. Remifentanil preconditioning substantially decreased the neurological score of rats (p<0.01), cerebral infarct size (p<0.01), neuronal apoptosis level (p<0.01), ROS level in neurons (p<0.01), MDA content (p<0.01) and expression levels of cysteinyl aspartate specific proteinase-3 (Caspase-3), NR2B, phosphorylated CaMKIIα (p-CaMKIIα) and p-cAMP responsive element binding protein (p-CREB) (p<0.01), but it increased the mitochondrial membrane potential (p<0.01) and B-cell lymphoma 2 (Bcl-2)/Bcl-2-associated X protein (Bax) ratio (p<0.01). Remifentanil can repress the NR2B/ CaMKIIα signaling pathway in the neurons of rats with cerebral IRI to decrease the p-CREB expression, ROS level and MDA content in neurons, neuronal apoptosis level and cerebral infarct size, and increase the mitochondrial membrane potential, thereby protecting the neurological function.

STYK1 promotes the malignant progression of laryngeal squamous cell carcinoma through targeting TGF-ß1.

OBJECTIVE: The aim of this study was to uncover the expression characteristic and biological function of STYK1 in the progression of laryngeal squamous cell carcinoma (LSCC), and to explore the underlying mechanism. PATIENTS AND METHODS: Expression level of STYK1 in 44 paired LSCC and adjacent normal tissues was detected by quantitative real-time polymerase chain reaction (qRT-PCR). The relationship between STYK1 level and clinical parameters of LSCC patients was analyzed. Subsequently, the regulatory effect of STYK1 on the proliferative ability of AMC-HN-8 and Hep-2 cells was evaluated by cell counting kit-8 (CCK-8) assay and colony formation assay. Dual-Luciferase reporter gene assay and rescue experiments were conducted to uncover the role of STYK1/TGF-ß1 axis in regulating the progression of LSCC. RESULTS: STYK1 was significantly up-regulated in LSCC tissues than that of adjacent normal tissues (p<0.05). LSCC patients with high expression level of STYK1 exhibited significantly higher clinical stage and lower survival rate (p<0.05). Knockdown of STYK1 remarkably attenuated viability and clonality in Hep-2 cells, while overexpression of STYK1 achieved the opposite trends in AMC-HN-8 cells (p<0.05). TGF-ß1 was confirmed to be the direct target binding STYK1, whose expression level was negatively regulated by STYK1. TGF-ß1 was significantly down-regulated in LSCC tissues  (p<0.05). Meanwhile, its low expression predicted significantly poor prognosis of LSCC patients. In addition, TGF-ß1 was responsible for STYK1-regulated malignant progression of LSCC. CONCLUSIONS: STYK1 is upregulated in LSCC and is closely associated with T stage and poor prognosis. Furthermore, STYK1 promotes the proliferative ability of LSCC cells through targeting TGF-ß1, thus aggravating the malignant progression of LSCC.