Low Dose Theophylline Showed an Inhibitory Effect on the Production of IL-6 and IL-8 in Primary Lung Fibroblast from Patients with COPD

Chronic obstructive pulmonary disease (COPD) is characterized by the abnormal and chronic lung inflammation. We hypothesized that lung fibroblasts could contribute to the local inflammation and investigated whether low dose theophylline had a beneficial effect on fibroblasts inflammation. Subjects undergoing lobectomy for bronchial carcinoma were enrolled and divided into COPD and control groups according to spirometry. Primary human lung fibroblasts were cultured from peripheral lung tissue distant to tumor tissue. There was a significant increase in both the mRNA expressions and protein levels for IL-6 and IL-8 in fibroblasts in COPD group, and the values were negatively correlated with lung function (P < 0.05). For COPD fibroblasts, the protein levels of IL-6 and IL-8 decreased from 993.0 ± 738.9 pg/mL to 650.1 ± 421.9 pg/mL (P = 0.014) and from 703.1 ± 278.0 pg/mL to 492.0 ± 214.9 pg/mL (P = 0.001), respectively, with 5 μg/mL theophylline treatment. In addition, theophylline at the dose of 5 μg/mL reduced the increased production of IL-6 and IL-8 induced by 1 μg/mL LPS in primary human lung fibroblasts. Our data suggest that lung fibroblasts participate in the chronic inflammation in COPD by releasing IL-6 and IL-8, and low dose theophylline can alleviate the proinflammatory mediators' production by fibroblasts

Plasma Orexin-A Levels in COPD Patients with Hypercapnic Respiratory Failure

Orexins have previously been shown to promote wakefulness, regulate lipid metabolism and participate in energy homeostasis. The aim of the study was to determine the relationship between plasma orexin-A and body composition in COPD in-patients with hypercapnic respiratory failure. 40 patients with hypercapnic respiratory failure and 22 healthy individuals were enrolled prospectively in this study. Plasma orexin-A levels, BMI, SaO2, PaCO2 and PaO2 were noted for all the patients. Plasma orexin-A levels were higher in the underweight (UW) group, normal weight (NW) group and overweight (OW) group of COPD patients as compared with UW, NW and OW group of the control group (P < .05). Plasma orexin-A in COPD patients were higher in the OW group than in the NW group and the UW group. Plasma orexin-A levels showed significant correlation with body mass index (BMI), independent of PaO2 (r = 0.576; P < .05) and %fat (r = 0.367; P < .05); a negative correlation was noted between plasma orexin-A levels and PaO2 (r = −0.738; P < .05) and SaO2 (r = −0.616; P < .05). Our results suggest that orexin-A levels are high in COPD patients with hypercapnic respiratory failure, and vary according to BMI and body composition. Orexin-A may be associated with the severity of hypoxemia in COPD patients with hypercapnic respiratory failure

Involvement of TRPC Channels in Lung Cancer Cell Differentiation and the Correlation Analysis in Human Non-Small Cell Lung Cancer

The canonical transient receptor potential (TRPC) channels are Ca2+-permeable cationic channels controlling the Ca2+ influx evoked by G protein-coupled receptor activation and/or by Ca2+ store depletion. Here we investigate the involvement of TRPCs in the cell differentiation of lung cancer. The expression of TRPCs and the correlation to cancer differentiation grade in non-small cell lung cancer (NSCLC) were analyzed by real-time PCR and immunostaining using tissue microarrays from 28 patient lung cancer samples. The association of TRPCs with cell differentiation was also investigated in the lung cancer cell line A549 by PCR and Western blotting. The channel activity was monitored by Ca2+ imaging and patch recording after treatment with all-trans-retinoic acid (ATRA). The expression of TRPC1, 3, 4 and 6 was correlated to the differentiation grade of NSCLC in patients, but there was no correlation to age, sex, smoking history and lung cancer cell type. ATRA upregulated TRPC3, TRPC4 and TRPC6 expression and enhanced Ca2+ influx in A549 cells, however, ATRA showed no direct effect on TRPC channels. Inhibition of TRPC channels by pore-blocking antibodies decreased the cell mitosis, which was counteracted by chronic treatment with ATRA. Blockade of TRPC channels inhibited A549 cell proliferation, while overexpression of TRPCs increased the proliferation. We conclude that TRPC expression correlates to lung cancer differentiation. TRPCs mediate the pharmacological effect of ATRA and play important roles in regulating lung cancer cell differentiation and proliferation, which gives a new understanding of lung cancer biology and potential anti-cancer therapy. © 2013 Jiang et al

ATF2 predicts poor prognosis and promotes malignant phenotypes in renal cell carcinoma

Supplemental Figure S1. The confirmation of ATF2 knockdown and overexpression. Supplemental Figure S2. qRT-PCR analysis of indicated genes expression upon ATF2 knockdown and overexpression. Supplemental Table S1. Sequences of primers used for plasmid construction. Supplemental Table S2. Sequences of primers used for qRT-PCR. Supplemental Table S3. Sequences of primers used for ChIP-qPCR. Supplemental Table S4. Correlation of ATF2 expression and clinical characteristics in RCC patients. Supplemental Table S5. Univariate and multivariate analyses of factors associated with overall survival in RCC patients. Supplemental Table S6. Univariate and multivariate analyses of factors associated with disease-free survival in RCC patients. (DOCX 625 kb

Arabidopsis NMD3 Is Required for Nuclear Export of 60S Ribosomal Subunits and Affects Secondary Cell Wall Thickening

NMD3 is required for nuclear export of the 60S ribosomal subunit in yeast and vertebrate cells, but no corresponding function of NMD3 has been reported in plants. Here we report that Arabidopsis thaliana NMD3 (AtNMD3) showed a similar function in the nuclear export of the 60S ribosomal subunit. Interference with AtNMD3 function by overexpressing a truncated dominant negative form of the protein lacking the nuclear export signal sequence caused retainment of the 60S ribosomal subunits in the nuclei. More interestingly, the transgenic Arabidopsis with dominant negative interference of AtNMD3 function showed a striking failure of secondary cell wall thickening, consistent with the altered expression of related genes and composition of cell wall components. Observation of a significant decrease of rough endoplasmic reticulum (RER) in the differentiating interfascicular fiber cells of the transgenic plant stems suggested a link between the defective nuclear export of 60S ribosomal subunits and the abnormal formation of the secondary cell wall. These findings not only clarified the evolutionary conservation of NMD3 functions in the nuclear export of 60S ribosomal subunits in yeast, animals and plants, but also revealed a new facet of the regulatory mechanism underlying secondary cell wall thickening in Arabidopsis. This new facet is that the nuclear export of 60S ribosomal subunits and the formation of RER may play regulatory roles in coordinating protein synthesis in cytoplasm and transcription in nuclei

Growth factor for therapeutic angiogenesis in ischemic heart disease: A meta-analysis of randomized controlled trials

Aim: This study was designed to systematically evaluate the effects of growth factor (GF) for therapeutic angiogenesis on ischemic heart disease (IHD) by pooling the results of randomized controlled trials (RCTs).Methods and Results: PubMed, EMBASE, and CENTRAL databases were searched from inception to October 2022. RCTs, investigating the effects of GF therapy on IHD, were included. The risk bias of included study was assessed according to Cochrane tool. Weighted mean difference (WMD), calculated with fixed effect model or random effect model, was used to evaluate the effects of GF therapy on left ventricular ejection fraction (LVEF) and Canadian Cardiovascular Society (CCS) angina class. Relative risk (RR) was used to evaluate the effects of GF therapy on all-cause mortality, major adverse cardiovascular events (MACE) and revascularization. Meta-analysis, meta-regression analysis and publication bias analysis were performed by RevMan 5.3 or Stata 15.1 software. Twenty-nine studies involving 2899 IHD patients (1,577 patients in GF group and 1,322 patients in control group) were included. Compared with the control group, GF therapy did not reduce all-cause mortality (RR: 0.82; 95% CI: 0.54–1.24; p = 0.341), MACE [(RR: 0.83; 95% CI: 0.61–1.12; p = 0.227), revascularization (RR: 1.27, 95% CI: 0.82–1.96, p = 0.290) and CCS angina class (WMD: −0.08, 95% CI: −0.36 to 0.20, p = 0.560). However, GF therapy could increase LVEF during short-term follow-up (&lt;1 year).Conclusion: GF for therapeutic angiogenesis was beneficial for increasing LVEF during short-term follow-up (&lt;1 year), however, the therapy was not efficacious in decreasing all-cause mortality, MACE and revascularization