ESCO2 promotes lung adenocarcinoma progression by regulating hnRNPA1 acetylation.

BACKGROUND: Emerging evidence indicates that metabolism reprogramming and abnormal acetylation modification play an important role in lung adenocarcinoma (LUAD) progression, although the mechanism is largely unknown. METHODS: Here, we used three public databases (Oncomine, Gene Expression Omnibus [GEO], The Cancer Genome Atlas [TCGA]) to analyze ESCO2 (establishment of cohesion 1 homolog 2) expression in LUAD. The biological function of ESCO2 was studiedusing cell proliferation, colony formation, cell migration, and invasion assays in vitro, and mouse xenograft models in vivo. ESCO2 interacting proteins were searched using gene set enrichment analysis (GSEA) and mass spectrometry. Pyruvate kinase M1/2 (PKM) mRNA splicing assay was performed using RT-PCR together with restriction digestion. LUAD cell metabolism was studied using glucose uptake assays and lactate production. ESCO2 expression was significantly upregulated in LUAD tissues, and higher ESCO2 expression indicated worse prognosis for patients with LUAD. RESULTS: We found that ESCO2 promoted LUAD cell proliferation and metastasis metabolic reprogramming in vitro and in vivo. Mechanistically, ESCO2 increased hnRNPA1 (heterogeneous nuclear ribonucleoprotein A1) binding to the intronic sequences flanking exon 9 (EI9) of PKM mRNA by inhibiting hnRNPA1 nuclear translocation, eventually inhibiting PKM1 isoform formation and inducing PKM2 isoform formation. CONCLUSIONS: Our findings confirm that ESCO2 is a key factor in promoting LUAD malignant progression and suggest that it is a new target for treating LUAD.

Agmatinase promotes the lung adenocarcinoma tumorigenesis by activating the NO-MAPKs-PI3K/Akt pathway.

Lung adenocarcinoma (LUAD) is one of the leading causes of cancer-related death worldwide. There is an urgent need to uncover the pathogenic mechanism to develop new treatments. Agmatinase (AGMAT) expression and its association with clinicopathological characteristics were analyzed via GEO, Oncomine, and TCGA databases, and IHC staining in human LUAD specimens. An EdU cell proliferation kit, propidiumiodide staining, colony formation, cell migration, and invasion assays, and a xenograft tumor model were used to detect the biological function of AGMAT in LUAD. Furthermore, the expression level of nitric oxide (NO) was detected using a DAF-FMDA fluorescent probe or nitrite assay kit, and further validated with Carboxy-PTIO (a NO scavenger). The roles of three isoforms of nitric oxide synthases (nNOS, eNOS, and iNOS) were validated using L-NAME (eNOS inhibitor), SMT (iNOS inhibitor), and spermidine (nNOS inhibitor). AGMAT expression was up-regulated in LUAD tissues. LUAD patients with high AGMAT levels were associated with poorer prognoses. AGMAT promoted LUAD tumorigenesis in NO released by iNOS both in vitro and in vivo. Importantly, NO signaling up-regulated the expression of cyclin D1 via activating the MAPK and PI3K/Akt-dependent c-myc activity, ultimately promoting the malignant proliferation of tumor cells. On the whole, AGMAT promoted NO release via up-regulating the expression of iNOS. High levels of NO drove LUAD tumorigenesis via activating MAPK and PI3K/Akt cascades. AGMAT might be a potential diagnostic and therapeutic target for LUAD patients.

Cationic micellar nanoparticles for DNA and doxorubicin co-delivery.

Cationic micellar nanoparticles for chemotherapeutic drugs and therapeutic gene co-delivery were prepared based on a poly-(N-ε-carbobenzyloxy-l-lysine) (PZLL) and dendritic polyamidoamine (PAMAM) block copolymer (PZLL-D3). PZLL-D3 was synthesized by a copper-catalyzed azide alkyne cyclization (click) reaction between α-alkyne-PZLL and azide focal point PAMAM dendrons. Its structure was characterized by (1)H NMR and FTIR, and its buffering capability was determined by acid-base titration. MTT, agarose gel electrophoresis and flow cytometry studies showed that PZLL-D3 revealed low in vitro cytotoxicity, strong pDNA condensation ability, protection of pDNA against deoxyribonuclease I degradation and high gene transfection efficiency in 293T and HeLa cells. In addition, the micellar nanoparticles delivered pDNA and anticancer drug doxorubicin (DOX) simultaneously and efficiently to tumor cells, and the DOX loaded nanoparticles showed sustained in vitro release at pH=7.4 and 5.8.

[Distinguishing central from obstructive sleep apnea with chest wall surface electrodes].

OBJECTIVE: To determine whether or not diaphragm electromyography recorded from chest wall surface electrodes (EMGsur) can be used to distinguish central from obstructive sleep apnea. METHODS: Ten patients (age (44 ± 10) years, body mass index (25.9 ± 1.8) kg/m²) with suspected obstructive sleep apnea referred from Guangzhou Institute of Respiratory Disease were studied between January and September 2009. EMGsur and diaphragm electromyography from esophageal electrode (EMGeso) were recorded during conventional overnight full polysomnography. And chest-abdominal movement was measured with chest and abdominal bands. RESULTS: High-quality EMGsur and EMGeso were recorded in all subjects except for one who could not tolerate a multipair esophageal electrode. Excellent correlation was found between EMGsur and EMGeso during sleep including apnea events (r = 0.81 ± 0.06, P < 0.05). The central sleep apnea events diagnosed by EMGeso were exactly the same as those diagnosed by EMGsur. However, the central sleep apnea events diagnosed by EMGsur were less than those diagnosed by conventional thoracic-abdominal bands (7 ± 11 vs 28 ± 31, P < 0.05). CONCLUSION: EMGsur may be used to distinguish central from obstructive sleep apnea events.

Effects of tai chi on lower-limb myodynamia in the elderly people: a meta-analysis.

OBJECTIVE: To assess the effects of Tai Chi (Chinese shadow boxing exercise) for improving the lower-limb muscle strength in elderly people. METHODS: The PUBMED database (from 1950), EMBASE-ASP database (from 1974), Cochrane Library (from 1991), Elsevier sciences database (from 1990), OVID full text database (from 1997), Springer-link database (from 1997), The National Research Register database, ISI Web of knowledge (from 1963), Chinese Medical Citation Index/Chinese Medical Current Contents (CMCI/CMCC, from 1989), China Knowledge Resource Integrated Database (CNKI, from 1915), VIP database (from 1989), and Wanfang database (from 1977) have been searched only for the English and Chinese literatures updated to 10-30-2010. Two researchers independently assessed the methodological quality of studies, extracted and checked the data one another according to the include/exclude standards. Disagreement was resolved by discussions or with the third person. The Review Manage Software 5.0 was used for Meta-analysis. RESULTS: Eventually, 2 randomized controled studies and 2 non-randomized controled studies met the inclusion criteria, with 163 subjects involved in the present meta-analysis. The meta-analysis demonstrated that Tai Chi exercise could improve the ankle flexor/extensor muscle strength and the knee extensor/flexor muscle strength, tested with an isokinetic dynamometer. The limb muscle strength increased significantly after Tai Chi exercise (P < 0.01). CONCLUSION: The meta-analysis favours Tai Chi exercise for improving the lower-limb muscle strength in the older people.