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Previous studies on the longevity effect of pyrroloquinoline quinine (PQQ) on nematode worms have revealed that PQQ can enhance the antioxidant capacity of nematode worms, thus extending the lifespan of the worms. The induction and development of cellular senescence are closely connected with inflammatory reactions. The aim of this study was to determine the effect of PQQ and ageing factors on senescent cells. To this end, we cultivated human embryonic lung fibroblasts in nutrient solution with or without tumour necrosis factor‐alpha (TNF‐α) to establish an inflammaging model in vitro. The cells were preincubated with or without PQQ to determine if PQQ had any anti‐inflammaging effect. More senescent cells were detected with the addition of TNF‐α than without (P < .01). The ratio of senescent cells to non‐senescent cells in the TNF‐α group was greater than that in the control group (P < .01). When cells were preincubated with PQQ prior to TNF‐α treatment, there were fewer senescent cells than those in the control group, which was not pretreated with PQQ (P < .05). The same tendency was noted with regard to p21, p16, and Jagged1. In summary, we used TNF‐α, a well‐known pro‐inflammatory cytokine associated with inflammaging, to establish an in vitro inflammaging model and provided evidence that PQQ delays TNF‐α –induced cellular senescence and has anti‐inflammaging properties. [ABSTRACT FROM AUTHOR]

Accumulating evidence indicates that abnormal deposition of amyloid-β (Ab) peptide in the brain is responsible for endothelial cell damage and consequently leads to blood-brain barrier (BBB) leakage. However, the mechanisms underlying BBB disruption are not well described. We employed an monolayer BBB model comprising bEnd.3 cell and found that BBB leakage was induced by treatment with Aβ1-42, and the levels of tight junction (TJ) scaffold proteins (ZO-1, Claudin-5, and Occludin) were decreased. Through comparisons of the effects of the different components of Aβ1-42, including monomer (Aβ1-42-Mono), oligomer (Aβ1-42-Oligo), and fibril (Aβ1-42-Fibril), our data confirmed that Aβ1-42-Oligo is likely to be the most important damage factor that results in TJ damage and BBB leakage in Alzheimer's disease. We found that the incubation of bEnd.3 cells with Aβ1-42 significantly up-regulated the level of receptor for advanced glycation end-products (RAGE). Co-incubation of a polyclonal antibody to RAGE and Aβ1-42-Oligo in bEnd.3 cells blocked RAGE suppression of Aβ1-42-Oligo-induced alterations in TJ scaffold proteins and reversed Aβ1-42-Oligoinduced up-regulation of RAGE, matrix metalloproteinase (MMP)-2, and MMP-9. Furthermore, we found that these effects induced by Aβ1-42-Oligo treatment were effectively suppressed by knockdown of RAGE using small interfering RNA (siRNA) transfection. We also found that GM 6001, a broad-spectrum MMP inhibitor, partially reversed the Aβ1-42-Oligo-induced inhibitor effects in bEnd.3 cells. Thus, these results suggested that RAGE played an important role in Abinduced BBB leakage and alterations of TJ scaffold proteins, through a mechanism that involved up-regulation of MMP-2 and MMP-9. [ABSTRACT FROM AUTHOR]

Chronic Obstructive Pulmonary Disease (COPD) is a worldwide health problem associated with high morbidity and mortality, especially in elderly patients. Aging functions include mitochondrial dysfunction, cell-to-cell information exchange, protein homeostasis and extracellular matrix dysregulation, which are closely related to chronic inflammatory response and oxidation-antioxidant imbalance in the pathogenesis of COPD. COPD displays distinct inflammaging features, including increased cellular senescence and oxidative stress, stem cell exhaustion, alterations in the extracellular matrix, reduced levels of endogenous anti-inflammaging molecules, and reduced autophagy. Given that COPD and inflammaging share similar general features, it is very important to identify the specific mechanisms of inflammaging, which involve oxidative stress, inflammation and lung mesenchymal stem cell function in the development of COPD, especially in elderly COPD patients. In this review, we highlight the studies relevant to COPD progression, and focus on mechanisms associated with inflammaging., Competing Interests: Conflict of interests The authors have no competing interests to declare., (Copyright: © 2019 Xia et al.)

Gax gene is a newly found negative transcriptional regulator of cells proliferation. This paper introduces the detection and structural features of Gax, details the inhibitory effect of Gax on the proliferation of vascular smooth muscle cells, vascular endothelial cells and cancer cells, and explains the putative mechanisms therein involved. The potential for providing therapeutic insights into human diseases by modulating Gax activity is prospected.

Background: Apoptosis is closely related to development of lung cancer. It is a strategy of lung cancer therapy to induce apoptosis. The aim of this study is to explore the effects of growth arrest-specific homeobox (Gax) transfection on apoptosis and expression of Bcl-2 and Bax proteins of human lung adenocarcinoma A549 cells., Methods: A549 cells were transfected with Gax gene by a replication-deficient adenovirus expressing the hemagglutinin-tagged Gax cDNA (Ad-Gax). Apoptosis of A549 cells was observed by transmission electronic microscope and terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL) positive staining. Apoptotic rate of A549 cells was evaluated by flow cytometry. Expressions of Bcl-2 and Bax proteins in A549 cells were detected by immunocytochemistry., Results: Before Ad-Gax transfection, none or few of TUNEL-positive A549 cells were detected. After Ad-Gax transfection, a marked increase in TUNEL-positive staining occurred, especially at 24 h later. The ratio of apoptosis of A549 cellsin non-transfection group and transfection groups at 12 h, 24 h, 48 h were 0.25%, 12.57%, 17.29%, 15.03%, respectively. Compared with non-transfection group, the apoptotic rates of transfection groups increased significantly (Chi-square value was 7.357, 11.126 and 9.943 respectively, P < 0.01). The average optical density (AOD) of Bcl-2 protein in A549 cells in non-transfection group and transfection groups at 12 h, 24 h, 48 h were 2.02±0.07, 1.79±0.02, 1.25±0.51 and 1.21±0.24 respectively. Compared with non-transfection group, AOD of Bcl-2 protein in A549 cells in transfection groups decreased significantly (t value was 6.651, 7.089 and 7.438 respectively, P < 0.01). On the other hand, Bax protein expression in transfection groups increased, the AODs of Bax were 4.49±0.61, 4.24±0.37 and 3.95±0.43, respectively. Compared with non-transfection group (3.12±0.42), AOD of Bax protein in A549 celle in transfection groups increased significantly (t value was 7.469, 7.287 and 6.473 respectively, P < 0.01). In the Ad-Gax transfection groups the lower Bcl-2/Bax ratio was, the higher the apoptotic rate of A549 cells was (r=-0.49, P < 0.01)., Conclusions: Ad-Gax transfection can induce A549 cells apoptosis. Possible mechanism is that Gax can downregulate Bcl-2 protein expression and upregulate Bax protein expression, and A549 cells apoptosis is related to the Bcl-2/Bax ratio.

Background: Lung cancer is the leading cancer of malignant tumor in China.It is the direction that poeple make efforts to seek gene therapy of lung cancer. The aim of this study is to explore the effects of transfected growth arrest-specific homeobox gene (Gax gene) on the proliferation and expressions of c-fos and c-jun mRNA in A549 cells., Methods: A549 cells were transfected with Gax gene by adenovirus. Expressions of Gax mRNA and protein were detected by RT-PCR and immunocytochemistry. The expressions of c-fos and c-jun mRNA were evaluated by RT-PCR. The proliferation inhibition effect of Gax transfection on A549 cells was evaluated by MTT assay., Results: Only in the A549 cells transfected with Gax gene the Gax expression was confirmed by RT-PCR and immunocytochemistry. Compared with that in the control group, c-fos and c-jun mRNA level decreased significantly in Gax-transfected A549 cells (t=7.755, P < 0.01; t= 5.938 , P < 0.01). MTT assay showed that the proliferation inhibition rates of A549 cells transfected by Ad-Gax for 24h, 48h and 72h were (47.35±5.36)%, (54.96±1.78)%, and (65.39±5.11)% respectively. And these proliferation inhibition rates were significantly higher than those in the control group (Chi-Square=7.152, 9.431 and 12.847, P < 0.01)., Conclusions: Gax gene can inhibit the proliferation of A549 cells. Its molecular mechanism may be through down-regulating the expressions of c-fos and c-jun.