Taraxasterol exhibits dual biological effects on anti-aging and anti-cancer in lung cells.

As numerous countries around the world have entered an aging society currently, understanding the impact of aging on human health becomes critically important. Notably, aging is associated with increased prevalence of age-related diseases, with the lungs being particularly susceptible. Aging contributes to a decline in lung function, including respiratory disorders, inflammation, and oxidative stress. Therefore, it is a very important to identify and develop active substances that can mitigate lung cell aging. In current study, we evaluated the impact of Taraxasterol on lung cell senescence, showing that Taraxasterol can alleviate lung cell senescence, as evidenced by reductions in senescence-related marker molecules, including p16 and p21. Additionally, Taraxasterol was found to ameliorate inflammation and oxidative stress in lung cells. Further mechanistic studies indicated that Taraxasterol exerts anti-aging effects through the PGC1α/NRF1 signaling pathway in lung cell models. Since aging is also closely related to lung cancer, we also explored the potential anti-tumor effect of taraxasterol. Utilizing non-small cell lung cancer cells (NSCLC) as a model, we systematically study the anti-tumor effect of Taraxasterol both in vivo and in vitro. Our findings suggest that Taraxasterol exhibited anti-cancer effect through EGFR-mediated signaling. Taken together, Taraxasterol shows dual biological activities, offering promising anti-aging and anti-lung cancer benefits.

Dietary Ochratoxin A Contamination Modulates Oxidative Stress, Inflammation Processes and Causes Fibrosis in in vitro and in vivo Lung Models.

BACKGROUND: The prevalence of aging-related diseases has increased significantly and this imposes a burden on both families and society. The lung is one of the few internal organs that is continuously exposed to the external environment, and lung aging is associated with a number of lung diseases. Ochratoxin A (OTA) is a toxin that is widely present in food and the environment but an effect for OTA on lung aging has not been reported. METHODS: Using both cultured lung cell and in vivo model systems, we studied the effect of OTA on lung cell senescence using flow cytometry, indirect immunofluorescence, western blotting, and immunohistochemistry. RESULTS: Results obtained showed that OTA caused significant lung cell senescence in cultured cells. Furthermore, using in vivo models, results showed that OTA caused lung aging and aging fibrosis. Mechanistic analysis showed that OTA upregulated the levels of inflammation and oxidative stress, and that this may be the molecular basis of OTA-induced lung aging. CONCLUSIONS: Taken together, these findings indicate that OTA causes significant aging damage to the lung, which lays an important foundation for the prevention and treatment of lung aging.

Ferulic acid alleviates lipopolysaccharide-induced acute lung injury through inhibiting TLR4/NF-κB signaling pathway.

Ferulic acid (FA) exhibits anti-inflammatory, antidiabetic, antihyperlipidemic, antioxidant, neuroprotective, and antihypertensive effects. This study aimed to determine whether FA could ameliorate lipopolysaccharide (LPS)-induced inflammatory responses and acute lung injury (ALI) in mice. Mice were challenged with LPS intratracheally to induce ALI 1 h after 3 days of FA (25, 50, and 100 mg/kg) or dexamethasone (DEX; 5 mg/kg) administration. The lung tissues and bronchoalveolar lavage fluid (BALF) were collected 12 h after the LPS challenge. Pretreatment with FA or DEX could attenuate lung histopathological change, complement deposition, and lung wet-to-dry weight ratio of mice injured by LPS. Meanwhile, the influx of neutrophils and macrophages, as well as the production of proinflammatory cytokine (tumor necrosis factor-alpha, interleukin 1 beta [IL-1ß], and IL-6), in BALF of ALI mice was significantly decreased. Moreover, FA or DEX markedly reversed the LPS-induced elevation of myeloperoxidase activity and monocyte chemoattractant protein-1 level in lung tissues of ALI mice. In addition, the Western blot analysis demonstrated that FA or DEX effectively inhibited the LPS-induced activation of the toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) signaling pathway in lung tissues. The current study suggested that the alleviating effect of FA against LPS-induced ALI might be partially due to the inhibition of the inflammatory response via inactivation of the TLR4/NF-κB signaling pathway.

Antibacterial potential of Forsythia suspensa polysaccharide against resistant Enterobacter cloacae with SHV-12 extended-spectrum ß-lactamase (ESBL).

In this study, a homogenous polysaccharide (FSP), with an average molecular weight of 9.08 × 104  Da, was isolated from Forsythia suspense and its antibacterial potential against Enterobacter cloacae producing SHV-12 ESBL was investigated. Growth kinetics, in vitro competition and biofilm formation experiments demonstrated that SHV-12 ESBL contributed to a fitness benefit to E cloacae strain. The antibacterial activity of FSP (2.5, 5.0 and 10.0 µg/mL) was tested against E cloacae bearing SHV-12 ESBL gene using bacterial sensitivity, agar bioassay and agar well diffusion assays. It was found that the addition of FSP demonstrated potent antibacterial activities against this bacterial as showed by the decrease of bacterial growth and the increase of the inhibition zone diameter. Furthermore, SHV-12 ESBL gene expression was decreased in E cloacae strain following different FSP treatment in a concentration-dependent manner. In conclusion, these data showed that FSP exhibited potent good antibacterial activity against E cloacae producing SHV-12 ESBL via inhibition of SHV-12 ESBL gene expression, which may promote the development of novel natural antibacterial agents to treat infections caused by this drug-resistant bacterial pathogen.

Yunnan Baiyao reduces hospital-acquired pressure ulcers via suppressing virulence gene expression and biofilm formation of Staphylococcus aureus.

Yunnan Baiyao (YB) as a kind of famous Chinese herbal medicine, possessed hemostatic, invigorating the circulation of blood, and anti-inflammatory effects. Identifying strategies to protect patients at risk for hospital-acquired pressure ulcers (HAPU) is essential. Herein, our results showed that YB treatment can effectively reduce the acne wound area and improve efficacy in a comparative study of 60 cases HAPU patients with S. aureus positive of acne wound pathogens. Furthermore, YB inhibited HIa expression and suppressed accessory gene regulator (agr) system controlled by regulatory RNA II and RNA III molecule using pALC1740, pALC1742 and pALC1743 S. aureus strain linked to gfpuvr reporter gene. Moreover, YB downregulated cao mRNA expression and inhibited coagulase activity by RT-PCR, slide and tube coagulase test. Additionally, YB downregulated seb, sec, sed, and tsst-1 mRNA expression to suppress enterotoxin and tsst-1 secretion and adhesion function related genes sarA, icaA, and cidA mRNA expression. Taken together, the data suggest that YB may reduce HAPU via suppressing virulence gene expression and biofilm formation of S. aureus.

A polysaccharide from Hedyotis diffusa interrupts metastatic potential of lung adenocarcinoma A549 cells by inhibiting EMT via EGFR/Akt/ERK signaling pathways.

In this study we investigated the potential effects of a polysaccharide (HDP) from Hedyotis diffusa on the metastasis in human lung adenocarcinoma A549 cells. HDP (25, 50 and 100µg/ml) significantly suppressed the cell adhesion, invasion and migration of A549 cells in a dose dependent manner by downregulation of matrix metalloproteinase (MMP-2 and MMP-9) and upregulation of tissue inhibitors of metalloproteinase (TIMP-2 and TIMP-9). Moreover, HDP effectively downregulated the protein expressions of epithelial-mesenchymal transition (EMT) markers (N-cadherin and vimentin), and upregulated E-cadherin protein expression, which is involved in interrupting EGFR/Akt/ERK signaling pathways, as well as inhibiting COX-2 protein expression. All these results demonstrated that HDP might be a novel anti-metastatic agent for NSCLC treatment.

Purification and characterization a polysaccharide from Hedyotis diffusa and its apoptosis inducing activity toward human lung cancer cell line A549.

In this study, we first isolated and purified a homogeneous polysaccharide (HDP) from Hedyotis diffusa. Its molecular weight was estimated to be about 89 kDa and GC analysis identified that it was composed of glucose, galactose, and mannose in a molar ratio of 2.0:1.0:1.0. Treatment with HDP (25, 100, and 200 µg/ml) resulted in growth inhibitory effect on A549 cells by inducing apoptosis. Moreover, induction of apoptosis by HDP was accompanied with the release of cytochrome c from mitochondria into the cytosol prior to the activation of caspase-9 and -3 in A549 cells. Also, a higher ratio of Bax/Bcl-2 proteins was observed in A549 cells followed by HDP treatment. Additionally, in vivo study showed that HDP (50 and 100 mg/kg) could suppress the growth of A549 subcutaneous xenograft tumors. Taken together, these results indicated that the HDP exerted an anticancer effect in vitro and in vivo and may be useful as a potent antitumor agent for the prevention of lung cancer.

High expression of miR-493-5p positively correlates with clinical prognosis of non small cell lung cancer by targeting oncogene ITGB1.

Increasing evidence supports that microRNA (miRNA)-mediated gene regulation plays a significant functional role in cancer progression. To investigate the expression and clinical significance of ITGB1 in non small cell lung cancer (NSCLC), the expression levels of ITGB1 in NSCLC tissues and human normal lung tissues were analyzed in silico using genes microarray, KEGG pathway and hierarchical clustering analysis followed by validation with quantitative RT-PCR. Our results showed that ITGB1 was upregulated in NSCLC tissues when compared with normal lung tissues. Survival analysis based on the qRT-PCR data established that ITGB1 expression was attentively related to the prognosis of NSCLC, and patients with higher ITGB1 expression had shorter overall survival (OS). Moreover, ITGB1 was confirmed to be a direct target of miR-493-5p. Furthermore, concomitant high expression of ITGB1 and low expression of miR-493-5p correlated with a shorter median OS and PFS in NSCLC patients. In conclusion, our results provide the first evidence that ITGB1 is a direct target of miR-493-5p suggesting that ITGB1 and miR-493-5p may have potential prognostic value and may be useful as tumor biomarkers for the diagnosis of NSCLC patients.

Association of antibiotic resistance with SHV-12 extended-spectrum ß-lactamase in Enterobacter cloacae.

The association between antibiotic resistance and SHV-12 extended-spectrum ß-lactamase (ESBL) in Enterobacter cloacae remains unknown. The aim of the present study was to investigate the prevalence of both chromosome- and plasmid-borne SHV-12 ESBL genes in Enterobacter cloacae. Transmission of the SHV-12 ESBL gene was explored, and the risk factors for antibiotic resistance in E. cloacae were analyzed. Polymerase chain reaction (PCR) results showed that 58 out of the 100 isolates carried the SHV-12 ESBL gene: 34.48% of them occurred in the chromosome, 48.28% were plasmid-borne and 17.24% appeared in both. Enterobacterial repetitive intergenic consensus-PCR tests detected 82 chromosomal genotypes. Conjugation assays showed that 70.00% of plasmid-borne SHV-12 ESBL genes were successfully transconjugated into E. coli C600 and that the antibiotic resistance phenotype of E. cloacae was partially (84%) or completely (10%) transferred. A significantly higher SHV-12 ESBL detection rate was found in patients with underlying conditions and/or complications compared with those without (P<0.05). The detection of SHV-12 ESBL-producing E. cloacae from vertical transmission varied significantly across clinical departments and age groups (P<0.05), with the highest rates in the intensive care unit and the group of patients aged ≥60 years. The present results indicate that the location and transmission efficiency of SHV-12 ESBL are closely correlated with the antibiotic resistance of E. cloacae.

Video-assisted thoracoscopic pneumonectomy: the anterior approach.

BACKGROUND: Video-assisted thoracoscopic surgery (VATS) lobectomy is now a well-accepted way to perform a minimally invasive lobectomy. VATS lobectomy is different from the conventional surgery. Different incisions, instruments and camera positions have also been described in the past two decades. There are no fixed patterns in VATS lobectomy. We here describe our method for fissure-based VATS lobectomy using an anterior approach. The aim of this paper is to show our technique for VATS lobectomy and our experience and outcomes obtained. METHODS: A 57-year-old man, who was admitted to the Affiliated Hospital of the Guangdong Medical College, had coughing up blood tinged sputum, right chest pain for one month. Thoracic CT imaging revealed a 22 mm × 22 mm × 20 mm, T1bN1M0 lesion in the right lower lobe. The patient for clinical stage II non-small cell lung cancer underwent VATS lobectomy by using an anterior approach on January 2013. RESULTS: Total volume of chest tube drainage after operation was 450 mL, intraoperative blood loss was 80 mL, operation time was 105.8 min, chest tube duration was three days, length of postoperative hospital stay was eight days. Follow-up no recurrence and metastasis for six months. CONCLUSIONS: The main advantages of the anterior approach in our experience are easy to deal with the absence or incomplete fissure by the "tunneling" approach. In addition, the mediastinal node packets are clearly seen, allowing thorough lymphadenectomy. Therefore, VATS lobectomy by the anterior approach is a safe, feasible procedure.