• CFTR
• diabetic retinopathy
• inflammatory level
• oxidative stress

• Compound glycyrrhiza oral solution
• SRC/MAPK pathway
• chronic obstructive pulmonary disease
• inflammation
• oxidative stress

Objective: To evaluate the effects of injectable platelet-rich fibrin (i-PRF) produced by a simple twice-centrifugation method combined with vacuum sealing drainage on wound inflammation and scar formation in chronic refractory wounds (CRW).

Methods: A total of sixty-eight patients with CRW who were admitted to our hospital were enrolled in this study. They were then randomly divided into the study group (n = 34) with being treated using negative pressure sealing and drainage technology, and the control group (n = 34) with being treated using injectable platelet-rich fibrin in conjunction with negative pressure sealing and drainage technology. The following were the primary outcomes: scar conditions at 1 and 3 months after the wound was fully healed, wound healing time, hospitalization time, wound healing rate, incidence of adverse reactions, serum inflammatory indices, and pain levels were assessed 1 day before treatment and 14 days after treatment. The secondary outcomes were determined by comparing the proportion of positive bacterial cultures in the two groups on the day before therapy, as well as on the seventh and fourteenth days after treatment.

Results: The wound healing time and hospital stay in the study group were significantly lower than that in the control group (all p < 0.001). The wound healing rate of the study group was significantly higher than that of the control group on the 14th day and 28th day after treatment (all p < 0.001). On the 14th day after treatment, the levels of WBC, CRP, and IL-6 in the study group were lower than those in the control group (all p < 0.001). The positive rate of bacterial culture in the study group was significantly lower than that in the control group on the 7th and 14th day after treatment (all p < 0.05). At 1 month and 3 months after treatment, the VSS score in the study group was lower than that in the control group (all p < 0.001). The total defect rate of the study group was also significantly lower than that of the control group (5.88% vs. 29.41%, p = 0.011).

Conclusion: The i-PRF produced by simple twice-centrifugation method combined with VSD could reduce wound inflammation and improve scar formation in patients with CRW.

Intestinal ischemia/reperfusion (I/R) injury is a fatal syndrome that occurs under many clinical scenarios. The apoptosis of intestinal cells caused by ischemia can cause cell damage and provoke systemic dysfunction during reperfusion. However, the mechanism of I/R-induced apoptosis remains unclear. Cystic fibrosis transmembrane conductance regulator (CFTR) is a cAMP-activated chloride channel. Few researchers have paid attention to its role in intestinal I/R injury, or the relationship between CFTR and intestinal apoptosis induced by hypoxia/reoxygenation (H/R).

To investigate the effects of CFTR on I/R-induced intestinal apoptosis and its underlying molecular mechanisms.

An intestinal I/R injury model was established in mice with superior mesenteric artery occlusion, and Caco2 cells were subjected to H/R for the simulation of I/R in vivo.

The results suggested that CFTR overexpression significantly increased the Caco2 cell viability and decreased cell apoptosis induced by the H/R. Interestingly, we found that the translocation of p65, an NF-κB member, from the cytoplasm to the nucleus after H/R treatment can be reversed by the overexpression of CFTR, the NF-κB P65 would return from the nucleus to the cytoplasm as determined by immunostaining. We also discovered that CFTR inhibited cell apoptosis in the H/R-treated cells, and this effect was significantly curbed by the NF-κB activator BA, AKT inhibitor GSK690693 and the PI3K inhibitor LY294002. Moreover, we demonstrated that CFTR overexpression could reverse the decreased PI3K/AKT expression induced by the I/R treatment in vivo or H/R treatment in vitro.

The results of the present study indicate that the overexpression of CFTR protects Caco2 cells from H/R-induced apoptosis; furthermore, it also inhibits H/R-induced apoptosis through the PI3K/AKT/NF-κB signaling pathway in H/R-treated Caco2 cells and intestinal tissues.

• Apoptosis
• Cystic fibrosis transmembrane conductance regulator
• Intestinal ischemia-reperfusion injury
• PI3K/AKT/NF-κB
• Hypoxia/reoxygenation
• Caco2 cells

• Animals
• Apoptosis
• Caco-2 Cells
• Cystic Fibrosis Transmembrane Conductance Regulator/metabolism
• Cystic Fibrosis Transmembrane Conductance Regulator/pharmacology
• Humans
• Ischemia
• Mice
• NF-kappa B/metabolism
• Phosphatidylinositol 3-Kinases/metabolism
• Proto-Oncogene Proteins c-akt/metabolism
• Reperfusion
• Signal Transduction

Chronic obstructive pulmonary disease (COPD) is mainly caused by cigarette smoking (CS), with oxidative stress being one key component during its pathogenesis. This study aimed to investigate the effects of quercitrin (QE) on cigarette smoke extract (CSE)-induced cell apoptosis and oxidative stress in human bronchial epithelial cells (HBECs) and its underlying mechanism. HBECs were treated with 2% CSE for 24 h to establish in vitro COPD cellular models. CCK-8 assay and flow cytometry analysis were performed to evaluate cell viability and apoptosis, respectively. Western blotting was applied to examine protein levels and ELISA kits were used to examine contents of the indicated oxidant/antioxidant markers. The results demonstrated that CSE promoted apoptosis and suppressed viability of HBECs and QE reversed these effects. CSE caused increase in T-AOC, superoxide dismutase, and glutathione (GSH) peroxidase contents and decrease in MDA, reactive oxygen species , and GSH contents in HBECs, which were rescued by QE treatment. The CSE-induced Nrf2 nuclear translocation and elevation of NAD(P)H: quinone oxidoreductase 1 (NQO1) and heme oxygenase-1 (HO-1) expression were also reversed by QE in HBECs. The mitogen-activated protein kinase (MAPK) signaling was activated by CSE and further suppressed by QE in HBECs. Collectively, QE exerts a protective role in HBECs against cell apoptosis and oxidative damage via inactivation of the Nrf2/HO-1/NQO1 pathway and the MAPK/ERK pathway.

It is commonly considered that COPD or at least emphysema represents accelerated lung aging induced in part by oxidative damage from cigarette smoke components. However, the issue if there are any aging signs in other organs in patients with COPD or emphysema remains unclear. The aim of this study is to explore whether there is multiple organ aging in the animal model of emphysema induced by cigarette smoke extract (CSE), and to ascertain the possible mechanisms, if any.

The animal model of emphysema was induced by CSE. Histomorphological changes in lung, heart, liver, kidney and spleen tissues were measured after staining with hematoxylin and eosin (H&E). The concentrations of stem cell factor (SCF), CyclinD1 and superoxide dismutase (SOD) in serum were determined by ELISA kit. The expressions of p16 (INK4a), Sca-1, eNOS proteins and mRNA in lung, heart, liver, kidney and spleen tissues were detected by Western blotting and quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), respectively. Decitabine (Dec) was applied to examine whether it could alter the changes caused by CSE.

The histomorphology of lung tissue was significantly changed, while other organs exhibited normal structure and histomorphology. The concentrations of SCF, CyclinD1 and SOD in serum were lower in the CSE group than in the control group. The expression levels of p16(INK4a) protein and mRNA in lung, heart, liver, kidney and spleen tissues were higher in the CSE group than in the control group, while the expression levels of Sca-1 and eNOS proteins and mRNA were lower in the CSE group than in the control group, in the tissues described above. Dec could partly alleviate the damages caused by CSE and the degree of alleviation resulted by Dec varied from organ to organ.

In addition to the aging of the lung tissue in the emphysema animal model induced by CSE, the tissues of the heart, liver, kidney and spleen were also in the progress of aging, but the sensibility and affinity of lung to CSE were higher than those of the other organs. Multiple organ aging may also exist in the animal model of emphysema induced by CSE. DEC can partly alleviate the multiple organ aging caused by CSE.

• CFTR modulators
• COPD
• cystic fibrosis transmembrane conductance regulator
• icenticaftor
• ivacaftor

Non–small cell lung cancer (NSCLC) is one of the most common causes of cancer-related mortality globally. However, the mechanism underlying NSCLC is not fully understood. Here, we investigated the role of cancer-related regulator of actin dynamics (CRAD) in NSCLC. We showed that CRAD was up-regulated in human NSCLC tissues and lung cancer cell lines. Lentivirus-mediated knockdown of CRAD repressed the proliferation and colony growth of A549 and H1299 cells. Apoptosis was enhanced by CRAD silencing in both cells, implicating that CRAD might maintain the survival of lung cancer cells. Microarray and bioinformatic assay revealed that CRAD directly or indirectly regulated diverse genes, including those involved in cell cycle and DNA damage repair. qRT-PCR and Western blot results confirmed the dysregulated genes as shown in microarray analysis. Claudin 4 was up-regulated in CRAD silenced A549 cells. The knockdown of Claudin 4 blocked the effects of CRAD on the expression of cell cycle and apoptosis effectors and enhanced the viability of A549 cells with CRAD down-regulation. Taken together, our findings demonstrate that CRAD acts as an oncogene in NSCLC at least partly through repressing Claudin 4.

• Apoptosis
• CARD
• Claudin 4
• NSCLC
• Proliferation

Cigarette smoke- (CS-) induced oxidative stress and inflammation in the lung are serious health problems. Primary and reprocessed tea products contain multiple antioxidants that have been reported to protect the lung against CS-induced injury. However, the beneficial effects of Eurotium cristatum fermented loose dark tea (ECT) and Eurotium cristatum particle metabolites (ECP) on CS-induced lung injury and its potential hepatic metabolic detoxification are still unclear. Therefore, sixty mice were randomly divided into six equal groups. CS-exposed mice were prevented or treated with ECP or ECT infusions for 12 or 8 weeks to determine the antioxidative stress, anti-inflammatory and potential metabolic detoxification of ECT and ECP. Thirty-six mice were randomly divided into six equal groups to observe the effects on hepatic metabolic detoxification by replacing daily drinking water with ECT. Results showed that CS significantly decreased the activities of glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) and upregulated the expressions of malondialdehyde (MDA), tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), IL-8, and IL-1β in serum. These adverse effects were modulated by ECP and ECT. In addition, ECT upregulated the mRNA expression of pregnane X receptor (PXR) and cytochrome P450 (CYP450) in the liver on daily free drinking ECT mice group. Western blot analysis further revealed that in CS-exposed mice, ECP and ECT significantly decreased the phosphorylation of mitogen-activated protein kinase (MAPK) in the lung but upregulated the protein expressions of PXR and aryl hydrocarbon receptor (AhR) in the liver. Overall, our findings demonstrated that ECT and ECP protected against lung injury induced by CS via MAPK pathway and enhanced hepatic metabolic detoxification via PXR and AhR pathways. Therefore, daily intake of ECT and ECP can potentially protect against CS-induced oxidative and inflammatory injuries.