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Colorectal cancer (CRC) is one of the top three malignant tumors in terms of morbidity, and the limited efficacy of existing therapies urges the discovery of potential treatment strategies. Immunotherapy gradually becomes a promising cancer treatment method in recent decades; however, less than 10% of CRC patients could really benefit from immunotherapy. It is pressing to explore the potential combination therapy to improve the immunotherapy efficacy in CRC patients. It is reported that Farnesoid X receptor (FXR) is deficiency in CRC and associated with immunity. Herein, we found that GW4064, a FXR agonist, could induce apoptosis, block cell cycle, and mediate immunogenic cell death (ICD) of CRC cells in vitro. Disappointingly, GW4064 could not suppress the growth of CRC tumors in vivo. Further studies revealed that GW4064 upregulated PD-L1 expression in CRC cells via activating FXR and MAPK signaling pathways. Gratifyingly, the combination of PD-L1 antibody with GW4064 exhibited excellent anti-tumor effects in CT26 xenograft models and increased CD8+ T cells infiltration, with 33% tumor bearing mice cured. This paper illustrates the potential mechanisms of GW4064 to upregulate PD-L1 expression in CRC cells and provides important data to support the combination therapy of PD-L1 immune checkpoint blockade with FXR agonist for CRC patients. [ABSTRACT FROM AUTHOR]

Methicillin-resistant Staphylococcus aureus (MRSA) infections are a major global health problem, and novel and effective antimicrobial drugs are urgently required to combat this life-threatening pathogen. Prodigiosin (PG) is a bacterial secondary metabolite with excellent anticancer and antibacterial properties. However, little is known about the antibacterial function of PG against MRSA. Therefore, the antibacterial efficacy of PG alone and PG in combination with different metal ions against clinic isolates of MRSA and methicillin-sensitive S. aureus (MSSA) strain was evaluated in the present study. The minimum inhibitory concentration of PG against both MRSA and MSSA was 0.25 μg/mL. However, 0.1 μg/mL PG showed a stronger inhibitory effect on MSSA cell growth (47.12%) than on MRSA cell growth (35.87%). Surprisingly, we observed a significant difference (p < 0.01) in membrane integrity between PG-treated MRSA and MSSA using the propidium iodide staining assay. Further, we found that in combination with PG, Zn2+, Al3+, and Cu2+ showed synergistic antibacterial effects against MRSA and MSSA. Our results could increase the current knowledge regarding the efficacy of PG in inhibiting the growth of different types of S. aureus clinical isolates and also offer a novel strategy for developing efficient antibacterial agents. [ABSTRACT FROM AUTHOR]

Long non-coding RNAs (lncRNAs) act as a member of competing endogenous RNAs (ceRNAs) and plays a significant role in tumorigenesis. The aim of this study was to identify potential lncRNA biomarkers for predicting the prognosis of lung squamous cell carcinoma (LUSC) using a comprehensive analysis of lncRNA mediated ceRNA network. Differentially expressed RNAs datasets were obtained using edge R package in 502 LUSC tissues and 49 adjacent non-LUSC tissues from the Cancer Genome Atlas (TCGA). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed to identify functional enrichment implication of lncRNA related differentially expressed mRNAs. Survival analysis was used Kaplan-Meier curve method. Univariate and multivariate Cox regression analysis were performed to construct a predictive model with lncRNA biomarkers. A total of 2185 lncRNAs, 170 miRNAs and 2053 mRNAs were differentially expressed between LUSC tissues and adjacent non-LUSC tissues. The novel constructed ceRNA network incorporated 184 LUSC-specific lncRNAs, 18 miRNAs, and 49 mRNAs. About 11 of 184 differentially expressed lncRNAs and 1 of 18 differentially expressed miRNAs and 5 of 49 differentially expressed mRNAs were conspicuously related to overall survival (p <.05). Univariate and multivariate cox regression analysis showed that 6 lncRNAs were retrieved to construct a predictive model to predict the overall survival in LUSC patients. In conclusion, CeRNAs contributed to the progression of LUSC and a model with 6 lncRNAs might be potential biomarker for predicting the prognosis of LUSC. [ABSTRACT FROM AUTHOR]

Prodigiosin extraction from driedSerratia marcescensjx1 cells using ultrasound-assisted extraction was optimized. The experiment was carried out in accordance with a central composite design (CCD) three-level and single-variable approach. The extraction time, extraction temperature, and solute to solvent ratio with the application of ultrasonication were optimized using response surface methodology (RSM) to maximize the extraction of prodigiosin from driedS. marcescensjx1 cells. The response of prodigiosin was determined using spectrophotometry. A quadratic model was established to predict the prodigiosin extraction yield. The analysis of variance showed that the quadratic model significantly contributed to the response of prodigiosin. The optimal extraction parameters were an extraction time of 17.5 min, an extraction temperature of 23.4°C, and a solvent-to-solute ratio of 1:27.2. Under these optimum conditions, the average prodigiosin yield was 4.3 g ± 0.02 g from 100 g of dried cells, which matches the predicted values. The obtained optimum conditions for prodigiosin extraction provide a scientific basis for the economical large-scale production of prodigiosin. [ABSTRACT FROM PUBLISHER]

Background. Recent reports have shown that miR-145 concentration correlates with infarct size. In this paper, we attempt to predict heart failure and cardiovascular death after acute myocardial infarction using circulating miR-145 concentration. Methods. We assessed 246 patients with first ST-segment-elevation myocardial infarction who underwent successful percutaneous coronary intervention. We measured circulating miR-145, N-terminal fragment of the precursor B-type natriuretic peptide, myocardial-band creatine kinase, and cardiac troponin-I concentrations on day 5 after primary percutaneous coronary intervention and assessed their correlations with long-term clinical outcome. Results. During the one-year follow-up period, 72 patients experienced primary composite cardiac events (cardiac death or hospitalization for worsening heart failure). Multivariable Cox proportional hazards analysis indicated that circulating miR-145 (hazard ratio 7.174, 95% confidence interval 4.208-12.229); p < 0.0001) was a significant independent predictor of cardiac events after adjustment for multiple confounders. Conclusion. Circulating miR-145 may be a novel biomarker for predicting long-term outcome after acute myocardial infarction. [ABSTRACT FROM AUTHOR]

Three 3-D coordination polymers, [Cu(cca)(4,4′-bipy)]n (1), [Co3(pda)3(1,10′-phen)2]n (2), and [Co(pda)(1,10′-phen)]n (3), have been synthesized from 4-carboxycinnamic acid (cca), 1,4′-phenylenediacrylic acid (pda), 4,4′-bipyridine (4,4′-bipy), 1,10′-phenanthroline (1,10′-phen), and Cu and Co salts under different conditions. The X-ray crystal structures of these three complexes are presented. Complex 1 exhibits a threefold 3-D α-Po interpenetration network. Complex 2 with a 3-D framework with six-connected single α-Po framework constructed from Co3 unit has been synthesized and characterized. Complex 3 shows a 3-D framework with bcu topology composed of 1-D rod-shaped secondary building units. Furthermore, the photocatalytic properties of 2 were studied. When excited by UV light, 2 exhibits photocatalytic activity, in 300 min, about 71% Rhodamine B decomposes. [ABSTRACT FROM AUTHOR]

We sequenced the complete mitochondrial genome sequencing of an important coronary heart disease model inbred rat strain for the first time. The total length of the mitogenome was 16,308 bp with 13 protein-coding genes, 2 ribosomal RNA genes, 22 transfer RNA genes. [ABSTRACT FROM AUTHOR]