ABSTRACT
Non-small-cell lung cancer (NSCLC), a common malignant tumor, requires deeper pathogenesis investigation. Autophagy is an evolutionarily conserved lysosomal degradation process that is frequently blocked during cancer progression. It is an urgent need to determine the novel autophagy-associated regulators in NSCLC. Here, we found that pirin was upregulated in NSCLC, and its expression was positively correlated with poor prognosis. Overexpression of pirin inhibited autophagy and promoted NSCLC proliferation. We then performed data-independent acquisition-based quantitative proteomics to identify the differentially expressed proteins (DEPs) in pirin-overexpression (OE) or pirin-knockdown (KD) cells. Among the pirin-regulated DEPs, ornithine decarboxylase 1 (ODC1) was downregulated in pirin-KD cells while upregulated along with pirin overexpression. ODC1 depletion reversed the pirin-induced autophagy inhibition and pro-proliferation effect in A549 and H460 cells. Immunohistochemistry showed that ODC1 was highly expressed in NSCLC cancer tissues and positively related with pirin. Notably, NSCLC patients with pirinhigh/ODC1high had a higher risk in terms of overall survival. In summary, we identified pirin and ODC1 as a novel cluster of prognostic biomarkers for NSCLC and highlighted the potential oncogenic role of the pirin/ODC1/autophagy axis in this cancer type. Targeting this pathway represents a possible therapeutic approach to treat NSCLC.
Subject(s)
Autophagy , Carcinoma, Non-Small-Cell Lung , Cell Proliferation , Disease Progression , Lung Neoplasms , Ornithine Decarboxylase , Female , Humans , Male , A549 Cells , Autophagy/genetics , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/metabolism , Cell Line, Tumor , Cell Proliferation/genetics , Gene Expression Regulation, Neoplastic , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Lung Neoplasms/metabolism , Ornithine Decarboxylase/metabolism , Ornithine Decarboxylase/genetics , Prognosis , Up-RegulationABSTRACT
Construction of the sterically demanding Csp2(oS)-Csp3(T) bond was achieved by carrying out the Pd-catalyzed carboxylate-directed Mizoroki-Heck reaction under extra-ligand-free aqueous conditions. The cooperative role of the presence of water with the absence of phosphine ligand was proposed to accelerate the migratory insertion process considerably, delivering a broad substrate scope.
ABSTRACT
INTRODUCTION: As a major public health problem, depression has a negative impact on individuals and society. The aim of this well-designed trial is to evaluate the efficacy and safety of electroacupuncture (EA) treatment for depression. METHODS/DESIGN: A 3-arm parallel, nonblinded, randomized controlled trial will be performed in 4 hospitals (centers). A total of 144 participants will be divided into 3 groups: EA group, manual acupuncture (MA) group, and western medicine group. Participants in EA group and MA group will receive 12 sessions of acupuncture treatment for 4 weeks. Participants allocated to western medicine group will only take 20âmg fluoxetine orally per day for 4 weeks. The primary outcome is Hamilton Depression Scale. Secondary outcomes are Self-Rating Depression Scale, Depression Scale of traditional Chinese medicine (Depression Scale of Traditional Chinese Medicine), brain fMRI and blood biomarkers including neurotransmitters serotonin, dopamine, noradrenaline, inflammatory cytokines inerleukin (IL)-1ß, tumor necrosis factor-α, IL-6, and neurotrophin BDNF. All the outcomes will be assessed at baseline, 4 weeks after EA treatment onset and 6-month follow-up. DISCUSSION: The results of this trial will verify the efficacy and safety of EA treatment for depressive patients and provide acupuncturists and clinicians with robust clinical evidence. TRIAL REGISTRATION: Chinese Clinical Trial Registry identifier: ChiCTR1900023420. Version 1. Registered on 26 May 2019. http://www.chictr.org.cn/edit.aspx?pid=37621&htm=4.
Subject(s)
Depression/therapy , Electroacupuncture/methods , Adult , Aged , Female , Humans , Male , Middle Aged , Multicenter Studies as Topic , Randomized Controlled Trials as Topic , Treatment OutcomeABSTRACT
Previous studies have confirmed the efficacy of acupuncture treatment for tinnitus. However, no relevant studies of the exact mechanism of acupuncture efficacy on tinnitus have been published. Enrolled participants with left-sided tinnitus received acupuncture treatment at TE3 and TE5. The acupuncture session lasted for 30 minutes. The infrared thermography (IRT) test of each participant's bilateral aural regions and visual analog scale scores were taken before and after the first acupuncture treatment session. Fifty-four participants accepted acupuncture treatment and the IRT test. The temperature differentials of both sides were reduced significantly, but the maximum, minimum, and average temperature of bilateral aural regions did not have a significant difference before and after acupuncture session. The acupuncture's effects for tinnitus were associated with the improvement of cochlear blood flow via the IRT test. We have planned a full-scale randomized controlled trial to find out more about the underlying mechanisms of acupuncture for tinnitus.