Potential Implications of the Lung Microbiota in Patients with Chronic Obstruction Pulmonary Disease and Non-Small Cell Lung Cancer.

Recently, chronic obstructive pulmonary disease (COPD) has been considered as a common risk factor of non-small cell lung cancer (NSCLC). However, very few studies have been conducted on the effects of COPD on the lung microbiota in patients with NSCLC. To identify the lung microbiota in patients with COPD and NSCLC (CN), the microbiome of the induced sputa of 90 patients was analyzed using 16S rDNA sequencing. The results showed no significant differences in the bacterial diversities of induced sputa among patients with COPD, NSCLC, and CN and no intrinsic differences among patients with different pathological types of lung cancer. After surgical operation, the diversities of the induced sputa in patients with CN significantly decreased. More remarkably, both the microbial community phenotypes and the components of the induced sputa in patients with CN obviously differed from those in patients with COPD or NSCLC. The relative abundances of Streptococcus, Veillonella, Moraxella, and Actinomyces significantly decreased, but those of Neisseria and Acinetobacter significantly increased in patients with CN compared with those in patients with COPD or NSCLC alone, resulting in increased Gram-negative microbiota and, therefore, in potential pathogenicity and stress tolerance, as well as in enhancement of microbial glycolipid metabolism, amino acid metabolism, and oxidative stress. Although COPD did not affect the number of pulmonary flora species in patients with NSCLC, these significant alterations in the microbial populations, phenotypes, and functions of induced sputa due to COPD would contribute to inflammation-derived cancer progression in patients with CN.

Herbal Active Ingredients: An Emerging Potential for the Prevention and Treatment of Papillary Thyroid Carcinoma.

Papillary thyroid carcinoma (PTC) is the most common subtype of differentiated thyroid cancers in Asian coastal cities, where the patients have increased risk of potentially high or excessive iodine intake. Given the high metastasis and recurrence of patients with BRAFV600E mutation, the mortality rate of thyroid cancer has recently shown an upward trend. A variety of therapies, including surgery, radiotherapy, and chemotherapy, have been used to treat thyroid cancer, but these therapies still have limitations, including postoperative complications, drug resistance, poor efficacy, or serious side effects. Recent studies have shown the potential of active ingredients derived from herbal medicine in inhibiting PTC via various cell signaling pathways. Some plant-derived compounds, such as apigenin, genistein, and curcumin, are also known to prevent and treat PTC. This article summarizes the recent advances in the structure-functional impact of anti-PTC active ingredients and their effects on PTC cells and tumor microenvironments with an emphasis on their challenges from basic research to clinical practice.

PBX3 Promotes Tumor Growth and Angiogenesis via Activation of AT1R/VEGFR2 Pathway in Papillary Thyroid Carcinoma.

PBX3 (Pre-B-cell leukemia homeobox 3) had been considered to be a multifunctional oncogene which involved in tumor growth, invasion, and metastasis in leukemia and some solid tumors. However, the contribution of PBX3 to papillary thyroid carcinoma (PTC) remains unclear. In this study, we found that PBX3 expression was significantly upregulated in PTC tissues compared to adjacent normal tissues, and high levels of PBX3 were correlated with tumor size, lymphatic metastasis, TMN stage, and poor prognosis of PTC patients. Overexpression of PBX3 in PTC cell lines promoted cell proliferation. Consistently, knockdown of PBX3 by shRNA induced cell cycle arrest at G0/G1 phase, and inhibited angiogenesis and tumor growth in vitro and in vivo. Furthermore, PBX3 promoted PTC cell proliferation and angiogenesis through activation of AT1R/VEGFR2 pathway while overexpression of AT1R and treatment with VEGFA reversed PBX3-shRNA-induced decreased phosphorylation of VEGFR2 and its downstream (ERK1/2, AKT and Src). It demonstrated that PBX3 could be used as a potential prognostic biomarker and therapeutic target for PTC.

Exosomal miR-1229 derived from colorectal cancer cells promotes angiogenesis by targeting HIPK2.

Circulating exosomal microRNAs (exomiR) have been demonstrated to be novel diagnostic biomarkers for various cancers. In this study, we found that circulating exomiR-1229 levels were significantly increased in the serum exosomes of patients with colorectal cancer (CRC) and significantly associated with tumor size, lymphatic metastasis, TNM stage and poor survival. Treatment with siRNA-Drosha, siRNA-ALIX and GW4869 repressed the expression of exomiR-1229 secreted from CRC cells. Both CRC-derived exosomes and exomiR-1229 mimic promoted the tubulogenesis of HUVECs, but transfection with exomiR-1229 inhibitor anta-miR-1229 significantly suppressed tube formation. Subsequently, HIPK2 was identified as a target of exomiR-1229 and responsible for the effect of exomiR-1229 on angiogenesis of HUVECs. ExomiR-1229 inhibited the protein expression of HIPK2, thereby activating VEGF pathway. Finally, anta-miR-1229 effectively inhibited tumor growth and angiogenesis in the nude mouse xenograft model. These results highlighted a novel mechanism of CRC angiogenesis and the biological roles of exomiR-1229.

PDGF signaling pathway in hepatic fibrosis pathogenesis and therapeutics (Review).

The platelet­derived growth factor (PDFG) signaling pathway exerts persistent activation in response to a variety of stimuli and facilitates the progression of hepatic fibrosis. Since this pathway modulates a broad spectrum of cellular processes, including cell growth, differentiation, inflammation and carcinogenesis, it has emerged as a therapeutic target for hepatic fibrosis and liver­associated disorders. The present review exhibits the current knowledge of the role of the PDGF signaling pathway and its pathological profiles in hepatic fibrosis, and assesses the potential of inhibitors which have been investigated in the experimental hepatic fibrosis model, in addition to the clinical challenges associated with these inhibitors.

Enhanced antitumor efficacy with combined administration of astragalus and pterostilbene for melanoma.

Astragalus, a commonly used traditional Chinese medicine, has exhibited antitumor actions in patients. In this study, in vitro and in vivo antitumor effects of astragalus and synergistic antitumor efficacy in combination with pterostilbene were investigated. Melanoma cells were treated with pterostilbene (Pt), graduated doses of astragalus injection (AI), or these in combination. Cell viability was measured using a MTT assay. Released nucleosomes and caspase activity were measured using enzyme-linked immunosorbent assay. Growth inhibition in vitro and in vivo was also assessed. Analysis of variance and t tests were used for statistical analysis. Significant reduction (p<0.05) in cellular proliferation were observed with AI and AI-Pt in a time- and concentration-dependent manner. Apoptosis and caspase-3/7 activity were significantly increased by AI and AI-Pt treatment (p<0.05). In vivo, AI inhibited melanoma tumor growth, with inhibition rates ranging from 36.5 to 62.3%, by inducing apoptosis via up-regulation Bax expression and the Bax/Bcl-2 ratio and down-regulating Bcl-2 expression. AI significantly inhibits the growth of melanoma in vitro and in vivo by inducing apoptosis. These data suggest that combined treatment of astragalus with pterostilbene enhances antitumor efficacy.

[Serum metalloproteinase-3 levels in assessing efficacy of Etanercept in patients with ankylosing spondylitis].

OBJECTIVE: To investigate the value of metalloproteinase-3 (MMP-3) levels in assessing efficacy of etanercept treatment in patients with ankylosing spondylitis (AS). METHODS: The serum and synovial fluid levels of MMP-3 were measured by enzyme linked immunosorbent assay (ELISA) in 48 patients with AS in week 0, 6 and 12; and also measured in 30 serum samples and 10 synovial fluid samples from healthy controls. RESULTS: The serum levels of MMP-3 in AS patients were significantly higher than those in controls. In AS patients, the MMP-3 levels in synovial fluid were significantly higher than those in serum levels. The serum MMP-3 levels in AS patients with peripheral arthritis were higher than those with exclusively axial involvement; while C-reactive protein (CRP) levels and erythrocyte sedimentation rate (ESR) did not differ between these 2 groups of AS. At week 6 and week 12 of etanercept treatment, the serum MMP-3 levels were significantly decreased (p<0.01) with the declining trend of ESR, CRP, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Bath Ankylosing Spondylitis Functional Index (BASFI) (all p<0.01). Before the etanercept treatment (week 0), serum levels of MMP-3 were correlated with ESR, CRP, BASDAI and BASFI (p<0.05). ESR was also correlated with CRP and BASFI, but not with BASDAI (r=0.361, P=0.071). At weeks 12, serum MMP-3 levels were still correlated with ESR, CRP and BASDAI (P<0.05), but not with BASFI (P=0.339); ESR was correlated with CRP, but not with BASDAI and BASFI. There was a significant correlation between BASDAI and BASFI (r=0.818,P=0.001). CONCLUSION: Serum MMP-3 levels are closely related to disease activity and may serve as an useful indicator for efficacy of etanercept treatment in AS patients.

[Construction of recombinant plasmid containing mouse vasoactive intestinal peptide gene and its expression in COS-7 cells].

OBJECTIVE: To construct the eukaryotic expression plasmid containing mouse vasoactive intestinal peptide(VIP) gene with biological activities. METHODS: VIP cDNA including the sequences of signal peptide was cloned from mouse thymus by RT-PCR, and then inserted into the mammalian expression vector pcDNA3.1 between Hind III and EcoR I restriction sites. COS-7 cells were transfected with pcDNA3. 1-VIP using liposome, the expression of VIP was identified by Western blot and ELISA. Supernatant of transfected cell culture was added to LPS-stimulated macrophages and the TNF-alpha production in cell medium was observed by ELISA. RESULTS: The cloned VIP cDNA was confirmed by enzyme digestion and DNA sequencing. The expression of VIP was detected in the pcDNA3. 1-VIP transfected COS-7 cells by Western blot and ELISA. The VIP in culture supernatant potently inhibited TNF-alpha production by LPS-induced Macrophages in vitro. CONCLUSION: The eukaryotic expression plasmid that expresses biological active murine VIP has been constructed successfully.

[Clinical evaluation of risk factors for coronary heart disease].

OBJECTIVE: To explore the relationship between risk factors for coronary heart disease (CHD) and coronary artery lesions. METHOD: Potential risk factors were studied in 341 patients underwent coronary angiography. RESULTS: (1) Coronary angiography showed coronary artery lesions in 214 patients (lesion group), and no lesion in 127 patients (non-lesion group). There was significant difference in age, past history of diabetes, family history of CHD, smoking history, high-density lipoprotein cholesterol (HDL-C), lower-density lipoprotein cholesterol (LDL-C), ratio of total cholesterol to HDL-C (TC/HDL-C), lipoprotein(a) [Lp(a)], fibrinogen (Fbg) and high-sensitivity C-reactive protein (hs-CRP) between two groups (P < 0.05). (2) There was significant correlation between severity of coronary artery lesions and hs-CRP, Lp(a), TC/HDL-C, Fbg, hyperlipidemia, TC, LDL-C and TG (with coefficients of correlation of 0.338, 0.250, 0.241, 0.207, 0.167, 0.147, 0.140 and 0.139; respectively, P < 0.05). (3) Analysis of receiver operating characteristics (ROC) curve for patients with coronary angiography and risk factors for CHD showed that the areas under ROC curve were 0.810, 0.669, 0.626, 0.625, 0.619 and 0.618 for hs-CRP, TC/HDL-C, Lp(a), Fbg, LDL-C and past history of hyperlipidemia, respectively. CONCLUSIONS: Past history of hyperlipidemia was a predictor for occurrence of CHD. Ratio of TC/HDL-C and blood level of Lp(a) could be used as predictors in screening for high blood lipid, which were much stronger than others. It is suggested that hs-CRP had an excellent predictive value in current coronary inflammatory lesions.