Melatonin enhances the anti-tumor effect of fisetin by inhibiting COX-2/iNOS and NF-κB/p300 signaling pathways.

Melatonin is a hormone identified in plants and pineal glands of mammals and possesses diverse physiological functions. Fisetin is a bio-flavonoid widely found in plants and exerts antitumor activity in several types of human cancers. However, the combinational effect of melatonin and fisetin on antitumor activity, especially in melanoma treatment, remains unclear. Here, we tested the hypothesis that melatonin could enhance the antitumor activity of fisetin in melanoma cells and identified the underlying molecular mechanisms. The combinational treatment of melanoma cells with fisetin and melatonin significantly enhanced the inhibitions of cell viability, cell migration and clone formation, and the induction of apoptosis when compared with the treatment of fisetin alone. Moreover, such enhancement of antitumor effect by melatonin was found to be mediated through the modulation of the multiply signaling pathways in melanoma cells. The combinational treatment of fisetin with melatonin increased the cleavage of PARP proteins, triggered more release of cytochrome-c from the mitochondrial inter-membrane, enhanced the inhibition of COX-2 and iNOS expression, repressed the nuclear localization of p300 and NF-κB proteins, and abrogated the binding of NF-κB on COX-2 promoter. Thus, these results demonstrated that melatonin potentiated the anti-tumor effect of fisetin in melanoma cells by activating cytochrome-c-dependent apoptotic pathway and inhibiting COX-2/iNOS and NF-κB/p300 signaling pathways, and our study suggests the potential of such a combinational treatment of natural products in melanoma therapy

Seeking for Correlative Genes and Signaling Pathways With Bone Metastasis From Breast Cancer by Integrated Analysis

Background: Bone metastasis frequently occurs in advanced breast cancer patients, and it is one of major causes of breast cancer associated mortality. The aim of the current study is to identify potential genes and related signaling pathways in the pathophysiology of breast cancer bone metastasis.Methods: Three mRNA expression datasets for breast cancer bone metastasis were obtained from Gene Expression Omnibus (GEO) dataset. The differentially expressed genes (DEGs) were obtained. Functional analyses, protein-protein interaction (PPI) network, and transcription factors (TFs)-target genes network was constructed. Real-time PCR using clinical specimens was conducted to justify the results from integrated analysis.Results: A 749 DEGs were obtained. Osteoclast differentiation and rheumatoid arthritis were two significantly enriched signaling pathways for DEGs in the bone metastasis of breast cancer. SMAD7 (degree = 10), TGFBR2 (degree = 9), VIM (degree = 8), FOS (degree = 8), PDGFRB (degree = 7), COL5A1 (degree = 6), ARRB2 (degree = 6), and ITGAV (degree = 6) were high degree genes in the PPI network. ETS1 (degree = 12), SPI1 (degree = 12), FOS (degree = 10), FLI1 (degree = 5), KLF4 (degree = 4), JUNB (degree = 4), NR3C1 (degree = 4) were high degree genes in the TFs-target genes network. Validated by QRT-PCR, the expression levels of IBSP, MMP9, MMP13, TNFAIP6, CD200, DHRS3, ASS1, RIPK4, VIM, and PROM1 were roughly consistent with our integrated analysis. Except PROM1, the other genes had a diagnose value for breast cancer bone metastasis.Conclusions: The identified DEGs and signaling pathways may make contribution for understanding the pathological mechanism of bone metastasis from breast cancer

Yupingfeng polysaccharide promote the growth of chickens via regulating gut microbiota

IntroductionYupingfeng polysaccharide (YPF-P) is the main substance of alcohol deposition in Yupingfeng powder, which has many biological functions such as enhancing immunity, repairing intestinal barrier and enhancing antioxidant ability. This study employed in vitro growth-promoting drug feed additives and animal experiments to comprehensively evaluate the use of YPF-P in broiler production.MethodsA total of 1,296 151 days-old Qingyuan Partridge chickens were randomly divided into four groups with six replicates and 54 hens per replicate: the control group was fed basal diet, and the experimental groups were fed diets supplemented with 4 g/kg, 8 g/kg, and 12 g/kg YPF-P for 14 days. Broilers were weighed before and at the end of the experiment to calculate total weight gain (GW), average daily gain (ADG), and feed compensation. At the end of the experiment, six chickens from each group were randomly selected for subwing vein blood sampling, which was used to measure serum biochemical indicators GHRH, GH, and IGF-1 by ELISA method. Randomly select chickens from control group and 8 g/kg group for slaughter, and cecal contents were collected for 16S high-throughput sequencing.ResultsDietary supplementation of 8 g/kg YPF-P can significantly increase the final body weight, total weight gain, average daily gain and decrease the feed to gain ratio of chickens. During 151–165 days, serum IGF-1 concentrations increased significantly (p < 0.05). There were no significant changes in serum GH concentration (p > 0.05). In terms of gut microbiota, there was no significant difference between control group and test group in Shannon index and Simpson index. Compared with the control group,the addition of 8 g/kgYPF-P significantly increased the abundance of Firmicutes and significantly decreased the abundance of Bacteroides at the phylum level.At the genus level, the relative abundance of unclassified_Oscillospiraceae was significantly increased and the unclassified_Muribaculaceae, uncultured_Bacteroidales_bacterium, Lactobacillus, Alloprevotella, Ligilactobacillus, Prevotellaceae_UCG_001, and unclassified_Atopobiaceae was significantly decreased.ConclusionThe above results showed that adding 8 mg/kg of YPF-P could increase the average daily gain of Qingyuan Partridge chickens, reduce the ratio of feed to meat, and affect the distribution proportion of intestinal microflora in chickens to some extent

BPTF promotes tumor growth and predicts poor prognosis in lung adenocarcinomas.

BPTF, a subunit of NURF, is well known to be involved in the development of eukaryotic cell, but little is known about its roles in cancers, especially in non-small-cell lung cancer (NSCLC). Here we showed that BPTF was specifically overexpressed in NSCLC cell lines and lung adenocarcinoma tissues. Knockdown of BPTF by siRNA significantly inhibited cell proliferation, induced cell apoptosis and arrested cell cycle progress from G1 to S phase. We also found that BPTF knockdown downregulated the expression of the phosphorylated Erk1/2, PI3K and Akt proteins and induced the cleavage of caspase-8, caspase-7 and PARP proteins, thereby inhibiting the MAPK and PI3K/AKT signaling and activating apoptotic pathway. BPTF knockdown by siRNA also upregulated the cell cycle inhibitors such as p21 and p18 but inhibited the expression of cyclin D, phospho-Rb and phospho-cdc2 in lung cancer cells. Moreover, BPTF knockdown by its specific shRNA inhibited lung cancer growth in vivo in the xenografts of A549 cells accompanied by the suppression of VEGF, p-Erk and p-Akt expression. Immunohistochemical assay for tumor tissue microarrays of lung tumor tissues showed that BPTF overexpression predicted a poor prognosis in the patients with lung adenocarcinomas. Therefore, our data indicate that BPTF plays an essential role in cell growth and survival by targeting multiply signaling pathways in human lung cancers

NMI inhibits cancer stem cell traits by downregulating hTERT in breast cancer.

N-myc and STAT interactor (NMI) has been proved to bind to different transcription factors to regulate a variety of signaling mechanisms including DNA damage, cell cycle and epithelial-mesenchymal transition. However, the role of NMI in the regulation of cancer stem cells (CSCs) remains poorly understood. In this study, we investigated the regulation of NMI on CSCs traits in breast cancer and uncovered the underlying molecular mechanisms. We found that NMI was lowly expressed in breast cancer stem cells (BCSCs)-enriched populations. Knockdown of NMI promoted CSCs traits while its overexpression inhibited CSCs traits, including the expression of CSC-related markers, the number of CD44+CD24- cell populations and the ability of mammospheres formation. We also found that NMI-mediated regulation of BCSCs traits was at least partially realized through the modulation of hTERT signaling. NMI knockdown upregulated hTERT expression while its overexpression downregulated hTERT in breast cancer cells, and the changes in CSCs traits and cell invasion ability mediated by NMI were rescued by hTERT. The in vivo study also validated that NMI knockdown promoted breast cancer growth by upregulating hTERT signaling in a mouse model. Moreover, further analyses for the clinical samples demonstrated that NMI expression was negatively correlated with hTERT expression and the low NMI/high hTERT expression was associated with the worse status of clinical TNM stages in breast cancer patients. Furthermore, we demonstrated that the interaction of YY1 protein with NMI and its involvement in NMI-mediated transcriptional regulation of hTERT in breast cancer cells. Collectively, our results provide new insights into understanding the regulatory mechanism of CSCs and suggest that the NMI-YY1-hTERT signaling axis may be a potential therapeutic target for breast cancers

Ku80 cooperates with CBP to promote COX-2 expression and tumor growth.

Cyclooxygenase-2 (COX-2) plays an important role in lung cancer development and progression. Using streptavidin-agarose pulldown and proteomics assay, we identified and validated Ku80, a dimer of Ku participating in the repair of broken DNA double strands, as a new binding protein of the COX-2 gene promoter. Overexpression of Ku80 up-regulated COX-2 promoter activation and COX-2 expression in lung cancer cells. Silencing of Ku80 by siRNA down-regulated COX-2 expression and inhibited tumor cell growth in vitro and in a xenograft mouse model. Ku80 knockdown suppressed phosphorylation of ERK, resulting in an inactivation of the MAPK pathway. Moreover, CBP, a transcription co-activator, interacted with and acetylated Ku80 to co-regulate the activation of COX-2 promoter. Overexpression of CBP increased Ku80 acetylation, thereby promoting COX-2 expression and cell growth. Suppression of CBP by a CBP-specific inhibitor or siRNA inhibited COX-2 expression as well as tumor cell growth. Tissue microarray immunohistochemical analysis of lung adenocarcinomas revealed a strong positive correlation between levels of Ku80 and COX-2 and clinicopathologic variables. Overexpression of Ku80 was associated with poor prognosis in patients with lung cancers. We conclude that Ku80 promotes COX-2 expression and tumor growth and is a potential therapeutic target in lung cancer

A prospective randomized study comparing the direct anterior approach in the lateral decubitus position versus the standard posterolateral approach for total hip arthroplasty

Background: This prospective randomized study was conducted to compare the early clinical, laboratory and radiological outcomes between patients who underwent the LDAA or the posterolateral approach (PLA) for THA.Methods: Seventy-two patients were randomly divided into two groups. The patients in one group accepted THA via the LDAA, and the patients in the other group accepted THA via the PLA. Results: Compared with the PLA, the LDAA offered the benefits of shorter incision (P < 0.001), less intraoperative blood loss (P < 0.001), less postoperative drainage (P < 0.001), and shorter length of stay (P < 0.001). In addition, the LDAA caused lower levels of creatine kinase, C-reactive protein, and myoglobin and higher levels of postoperative hemoglobin. The LDAA group received a lower score (P < 0.001) in the visual analogue scores and a higher score (P < 0.001) in the Harris hip scores. However, the LDAA required a longer operation time than the PLA (P < 0.001).Conclusions: Our results showed that LDAA is more minimally invasive and associated with a faster functional recovery

Effect of phosphoglucosamine mutase on biofilm formation and antimicrobial susceptibilities in M. smegmatis glmM gene knockdown strain.

UDP-N-acetylglucosamine (UDP-GlcNAc) is a direct glycosyl donor of linker unit (L-Rhamnose-D-GlcNAc) and an essential precursor of peptidoglycan in mycobacteria. Phosphoglucosamine mutase (GlmM) is involved in the formation of glucosamine-1-phosphate from glucosamine-6-phosphate, the second step in UDP-GlcNAc biosynthetic pathway. We have demonstrated that GlmM protein is essential for the growth of M. smegmatis. To facilitate the analysis of the GlmM protein function in mycobacteria, a tetracycline inducible M. smegmatis glmM gene knockdown strain was constructed by using an antisense RNA technology. After induction with 20 ng/ml tetracycline, the expression of GlmM protein in glmM gene knockdown strain was significantly decreased, resulting in a decline of cell growth. The morphological changes of glmM gene knockdown strain induced with 20 ng/ml tetracycline have been observed by scanning electron microscope and transmission electron microscope. Furthermore, insufficient GlmM protein reduced the biofilm formation and increased the sensitivity to isoniazid and ethambutol in M. smegmatis, indicating that GlmM protein had effect on the biofilm formation and the senstivity to some anti-tuberculosis drugs targeting the cell wall. These results provide a new insight on GlmM functions in mycobacteria, suggesting that GlmM could be a potential target for development of new anti-tuberculosis drug

Exploring approaches to contemporary clinical incident analysis methods within acute care settings: a scoping review protocol

Objective: This review will explore the literature on contemporary incident analysis methods used in acute hospital settings, identifying types and characteristics of these methods and how they are used to minimize, prevent, or learn from errors and improve patient safety. Introduction: Safety is a major focus in health care; however, despite best efforts, errors and incidents still occur, leading to harm or potential harm to patients, families, carers, staff, or the organization. Incident analysis methods aim to reduce risk of harm. Traditional methods have been criticized for failing to consider the complexity of health care and the dynamic nature of acute care settings. Alternative methodologies are being sought to achieve higher levels of patient safety and care quality care in hospitals. Learning from errors and communicating with those involved in incidents are key requirements in contemporary incident analysis. Inclusion criteria: This review will consider empirical research published since 2013, reporting on the use of clinical incident analysis methods within acute care settings. The review will explore ways in which consumers or stakeholders (eg, clinicians or other hospital workers, patients, families, carers, visitors) have been included in these analysis methods and how data have been used to support changes in the service or organization. Methods: Following JBI methods and PRISMA-ScR reporting guidance, we will search PubMed, CINAHL (EBSCOhost), Embase, Scopus, the Cochrane Library, Web of Science, and ProQuest Dissertations and Theses. Studies will be reviewed independently, with results presented in tables, figures, and narrative summaries according to the concepts of interest