Metastatic lung cancer is a life-threatening condition that develops when cancer in another area of the body metastasizes, or spreads, to the lung. Despite advances in our understanding of primary lung oncogenesis, the biological basis driving the progression from primary to metastatic lung cancer remains poorly characterized. Genetic knockdown of the particular genes in cancer cells were achieved by lentiviral-mediated interference. Invasion potential was determined by Matrigel and three-dimensional invasion. The secretion of matrix metalloproteinase 2 (MMP2) and MMP9 were measured by ELISA. Protein levels were assessed by Western blotting and immunohistochemistry. Protein-protein interactions were determined by immunoprecipitation. An experimental mouse model was generated to investigate the gene regulation in tumor growth and metastasis. Nck-associated protein 1 (NAP1/NCKAP1) is highly expressed in primary non-small-cell lung cancer (NSCLC) when compared with adjacent normal lung tissues, and its expression levels are strongly associated with the histologic tumor grade, metastasis and poor survival rate of NSCLC patients. Overexpression of NAP1 in lowly invasive NSCLC cells enhances MMP9 secretion and invasion potential, whereas NAP1 silencing in highly invasive NSCLC cells produces opposing effects in comparison. Mechanistic studies further reveal that the binding of NAP1 to the cellular chaperone heat shock protein 90 (HSP90) is required for its protein stabilization, and NAP1 plays an essential role in HSP90-mediated invasion and metastasis by provoking MMP9 activation and the epithelial-to-mesenchymal transition in NSCLC cells. Our insights demonstrate the importance and functional regulation of the HSP90-NAP1 protein complex in cancer metastatic signaling, which spur new avenues to target this interaction as a novel approach to block NSCLC metastasis.
26 January 2022 in Annals of Otology, Rhinology & Laryngology
Objective: The aim of this study is to create a nomogram for accurately predicting the prognosis of idiopathic sudden sensorineural hearing loss (ISSNHL) and provide a reference for clinical treatment. Methods: Three hundred and twenty-three patients with ISSNHL were admitted from September 2014 to November 2020. The clinical data were retrospectively reviewed. Prognostic factors for ISSNHL were assessed based on univariate and multivariate logistic regression analysis and used to create a nomogram. Nomogram performance in terms of predictive and discriminatory ability was evaluated by calculating the concordance index (C-index) and generating calibration plots. Results: The overall hearing improvement rate was 41.4%, comprising complete recovery (13.3%), marked recovery (17.0%), and slight recovery (11.1%). Multivariate logistic regression analysis showed that age, symptoms of vertigo, interval between onset and treatment, low-density lipoprotein, and type of hearing loss were independent predictors of ISSNHL. A nomogram based on these 5 factors had a C index of 0.798 (95% confidence interval 0.750-0.845). Conclusions: Age, vertigo, interval between onset and treatment, low-density lipoprotein level, and type of hearing loss are closely associated with hearing recovery. The nomogram may enable prediction of the prognosis of ISSNHL and facilitate clinical decision-making.
Background: To determine the influence of gender on the different pain subtypes experienced by patients with Parkinson’s disease (PD). Methods: Two hundred patients with PD were recruited for this research. Demographic features for all patients were recorded, as well as clinical data on age, disease duration, levodopa equivalent daily dose (LEDD), and scores for Unified Parkinson’s Disease Rating Scale-III (UPDRS III), Hoehn-Yahr Scale (H&Y), King’s Parkinson’s disease Pain Scale (KPPS), Pittsburgh Sleep Quality Index (PSQI), Mini-mental State Examination (MMSE), activities of daily living scale (ADL), Hamilton Depression Rating Scale (HAMD), and Hamilton Anxiety Rating Scale (HAMA) scales. Results: Male and female patients showed no significant differences in terms of age, disease duration, LEDD, H&Y stage, and UPDRS III, HAMD, HAMA, PSQI and ADL scores. Women showed significantly lower MMSE than men, but their KPPS scores were higher (both p < 0.05). Female also showed significantly higher scores for chronic, fluctuation-related pain and oro-facial pain and more discoloration;edema/swelling than males (p < 0.05). Conclusions: Female gender was associated with pain in PD patients, with stronger associations for certain subtypes of PD-related pain.
Background: The difference in spontaneous brain activity between acute subjective tinnitus patients (with or without hearing loss) and control participants was explored using the amplitude of low-frequency fluctuations and degree centrality methods through resting-state functional magnetic resonance imaging. The study aimed to provide an objective basis for clinical diagnosis and pathogenesis of patients with acute subjective tinnitus. Methods: Fourteen acute subjective tinnitus (AST) patients with hearing loss (AST-HL), 6 AST patients with no hearing loss (AST-NHL), and 14 healthy controls (HCs) with age, sex, and education status matched were recruited for this study. Resting-state functional magnetic resonance imaging (fMRI) examinations were performed in a resting state and the amplitude of low-frequency fluctuations (ALFF) and degree centrality (DC) values of each group were acquired. Statistical analysis was performed to assess the ALFF and DC values of different brain areas of the participants (AST-HL and AST-NHL were compared with HCs, but AST-HL and AST-NHL were not). Results: Patients with acute subjective tinnitus and hearing loss showed a significantly increased amplitude of low-frequency fluctuation values in the left middle temporal gyrus and bilateral frontal gyrus/marginal lobe/cingulate gyrus but a decreased amplitude of low-frequency fluctuations values in the bilateral superior temporal gyrus/anterior cerebellar lobe in comparison with healthy controls. The amplitude of low-frequency fluctuation values of patients with acute subjective tinnitus and hearing loss in the right posterior lobe of the cerebellum, bilateral temporal gyrus, bilateral lenticular nucleus, bilateral frontal gyrus, right inferior occipital gyrus, were higher, but were significantly lower in the bilateral anterior lobe of cerebellum/superior temporal gyrus and left posterior cerebellar lobe as compared with those of healthy controls. Degree centrality values in the healthy controls group were increased in the right superior marginal gyrus and decreased in the right thalamus in patients with acute subjective tinnitus and hearing loss, while patients with acute subjective tinnitus with no hearing loss presented significantly higher degree centrality values in the left frontal lobe and lower degree centrality values in the left center rear return. Conclusions: Aberrant amplitude of low-frequency fluctuations and values exist in various brain regions, indicating abnormal spontaneous brain activity in both acute subjective tinnitus and hearing loss and acute subjective tinnitus no hearing loss patients. The pathogenesis of acute subjective tinnitus may be related to abnormalities in both the auditory cortex and nonauditory cortex. These findings provide more evidence to help clarify the neuronal symptoms of acute subjective tinnitus patients.