Circular RNA circ_0020710 drives tumor progression and immune evasion by regulating the miR-370-3p/CXCL12 axis in melanoma.

BACKGROUND: Circular RNAs (circRNAs) have been reported to have critical regulatory roles in tumor biology. However, their contribution to melanoma remains largely unknown. METHODS: CircRNAs derived from oncogene CD151 were detected and verified by analyzing a large number of melanoma samples through quantitative real-time polymerase chain reaction (qRT-PCR). Melanoma cells were stably transfected with lentiviruses using circ_0020710 interference or overexpression plasmid, and then CCK-8, colony formation, wound healing, transwell invasion assays, and mouse xenograft models were employed to assess the potential role of circ_0020710. RNA immunoprecipitation, luciferase reporter assay and fluorescence in situ hybridization were used to evaluate the underlying mechanism of circ_0020710. RESULTS: Our findings indicated that circ_0020710 was generally overexpressed in melanoma tissues, and high level of circ_0020710 was positively correlated with malignant phenotype and poor prognosis of melanoma patients. Elevated circ_0020710 promoted melanoma cell proliferation, migration and invasion in vitro as well as tumor growth in vivo. Mechanistically, we found that high level of circ_0020710 could upregulate the CXCL12 expression via sponging miR-370-3p. CXCL12 downregulation could reverse the malignant behavior of melanoma cells conferred by circ_0020710 over expression. Moreover, we also found that elevated circ_0020710 was correlated with cytotoxic lymphocyte exhaustion, and a combination of AMD3100 (the CXCL12/CXCR4 axis inhibitor) and anti-PD-1 significantly attenuated tumor growth. CONCLUSIONS: Elevated circ_0020710 drives tumor progression via the miR-370-3p/CXCL12 axis, and circ_0020710 is a potential target for melanoma treatment.

Electronic Modulation of Pd-Based Bimetallic Catalysts with Sulfur-Doped Carbon Support for Phenylacetylene Semihydrogenation.

The semihydrogenation of phenylacetylene to styrene represents an important process for optimizing the polystyrene production and also a model reaction for the evaluation of selective hydrogenation catalysts. Although the alloying strategy and surface engineering for noble metal (particularly for Pd) catalysts can effectively inhibit the overhydrogenation of styrene, the selectivity of phenylacetylene semihydrogenation to styrene is generally below 95% near the full conversion. Here, we demonstrate the electronic modulation of Pd-based bimetallic nanocluster catalysts based on the strong metal-support interactions for improving the catalytic selectivity for phenylacetylene semihydrogenation. A series of Pd-M (M = Fe, Co, Ni, Cu, Ga) bimetallic nanoclusters of ∼2 nm are immobilized on mesoporous sulfur-doped carbon (meso_S-C) supports, which exhibit a high selectivity of >97% for the semihydrogenation of phenylacetylene to styrene. The strong interaction between metal and the meso_S-C supports enables the modulation of electronic structure of the bimetallic nanoparticles and thus leads to the selectivity enhancement for the phenylacetylene semihydrogenation.

Hsa-let-7b Suppresses Cell Proliferation by Targeting UHRF1 in Melanoma.

UHRF1 promotes melanoma progression by inducing cell proliferation, and is correlated with poor prognosis of melanoma patients. However, the regulation mechanism has not been fully elaborated. Here, we detected hsa-let-7b expression and its role in melanoma. Through Targetscan and miRanda predication, 30 overlapped miRNAs were found; further survival analysis revealed that hsa-let-7b was the only miRNA that affected the overall survival. Overexpressed hsa-let-7b could significantly inhibit the proliferation ability of A375 and A2058 cells, and this phenomenon was reversed after co-transfection with pLenti-UHRF1. In conclusion, hsa-let-7b regulates melanoma cells proliferation in vitro by targeting UHRF1.

A metal-catalyzed thermal polymerization strategy toward atomically dispersed catalysts.

We report a general metal-catalyzed thermal polymerization strategy for the preparation of atomically dispersed catalysts that consist of isolated metal atoms (Fe, Co and Ni) hosted by a polymer-like carrier containing phenanthroline substructure. The prepared atomically dispersed cobalt catalysts exhibit high selectivity, activity, and reusability in catalyzing aromatic alkane oxidation.

Downregulation of RNF128 activates Wnt/ß-catenin signaling to induce cellular EMT and stemness via CD44 and CTTN ubiquitination in melanoma.

BACKGROUND: Ring finger proteins (RNFs) were involved in carcinogenesis. Here, we aimed to explore the detailed mechanism of RNF128 in the progression of melanoma. METHODS: We reanalyzed several gene expression profiles from the Gene Expression Omnibus (GEO) database and obtained the overlapped differential expressed RNF genes. Among them, RNF128 was selected to further explore its expression, the biological significance, and the underlying molecular mechanism, as well as the clinical relevance in melanoma patients. RESULTS: RNF128 was found to be significantly downregulated in the selected datasets, which was further verified in our melanoma tissues. Moreover, RNF128 downregulation was shown to correlate with the malignant phenotype of melanoma, and further functional assays demonstrated that low levels of RNF128 promoted melanoma progression via inducing cell epithelial-mesenchymal transition (EMT) and the acquisition of stemness. Mechanistically, RNF128 interference activated the Wnt pathway via simultaneously ubiquitinating CD44/cortactin (CTTN), resulting in CD44 and c-Myc transcription, thus revealed that RNF128 participated in a positive feedback of the Wnt pathway-CD44 loop. Clinically, we found that patients expressing low RNF128 and high CD44/CTTN levels had a poor prognosis. CONCLUSION: Downregulated RNF128 activates Wnt signaling to induce cellular EMT and stemness by ubiquitinating and degrading CD44/CTTN, and RNF128 is a reliable diagnostic and prognostic biomarker, and a deeper understanding of RNF128 may contribute to the treatment of melanoma.

Bioinformatics-based analysis reveals elevated MFSD12 as a key promoter of cell proliferation and a potential therapeutic target in melanoma.

Although recent therapeutic advances based on our understanding of molecular phenomena have prolonged the survival of melanoma patients, the prognosis of melanoma remains dismal and further understanding of the underlying mechanism of melanoma progression is needed. In this study, differential expression analyses revealed that many genes, including AKT1 and CDK2, play important roles in melanoma. Functional analyses of differentially expressed genes (DEGs), obtained from the GEO (Gene Expression Omnibus) database, indicated that high proliferative and metastatic abilities are the main characteristics of melanoma and that the PI3K and MAPK pathways play essential roles in melanoma progression. Among these DEGs, major facilitator superfamily domain-containing 12 (MFSD12) was found to have significantly and specifically upregulated expression in melanoma, and elevated MFSD12 level promoted cell proliferation by promoting cell cycle progression. Mechanistically, MFSD12 upregulation was found to activate PI3K signaling, and a PI3K inhibitor reversed the increase in cell proliferation endowed by MFSD12 upregulation. Clinically, high MFSD12 expression was positively associated with shorter overall survival (OS) and disease-free survival (DFS) in melanoma patients, and MFSD12 was an independent prognostic factor for OS and DFS in melanoma patients. Therapeutically, in vivo assays further confirmed that MFSD12 interference inhibited tumor growth and lung metastasis in melanoma. In conclusion, elevated MFSD12 expression promotes melanoma cell proliferation, and MFSD12 is a valuable prognostic biomarker and promising therapeutic target in melanoma.

Andrographolide sulfonate ameliorates lipopolysaccharide-induced acute lung injury in mice by down-regulating MAPK and NF-κB pathways

Acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) is a severe, life-threatening medical condition characterized by widespread inflammation in the lungs, and is a significant source of morbidity and mortality in the patient population. New therapies for the treatment of ALI are desperately needed. In the present study, we examined the effect of andrographolide sulfonate, a water-soluble form of andrographolide (trade name: Xi-Yan-Ping Injection), on lipopolysaccharide (LPS)-induced ALI and inflammation. Andrographolide sulfonate was administered by intraperitoneal injection to mice with LPS-induced ALI. LPS-induced airway inflammatory cell recruitment and lung histological alterations were significantly ameliorated by andrographolide sulfonate. Protein levels of pro-inflammatory cytokines in bronchoalveolar lavage fluid (BALF) and serum were reduced by andrographolide sulfonate administration. mRNA levels of pro-inflammatory cytokines in lung tissue were also suppressed. Moreover, andrographolide sulfonate markedly suppressed the activation of mitogen-activated protein kinase (MAPK) as well as p65 subunit of nuclear factor-κB (NF-κB). In summary, these results suggest that andrographolide sulfonate ameliorated LPS-induced ALI in mice by inhibiting NF-κB and MAPK-mediated inflammatory responses. Our study shows that water-soluble andrographolide sulfonate may represent a new therapeutic approach for treating inflammatory lung disorders.

Application of continuous infusion of remifentanil during induction of general anesthesia in elderly patients / 上海第二医科大学学报

Objective To study the application of continuous infusion of remifentanil combined with propofol with different velocity du-ring induction of general anesthesia in elderly patients. Methods Sixty elderly patients were divided into 4 groups randomly(n=15) and given remifentanil with continuous infusion rate of 0.1,0.15,0.2 and 0.3 ?g?kg-1?min-1,respectively.After given midazolam and propofol,remifentanil infusion started with different velocity.Three minutes later,vecuronium was given and intubation performed 2 min later.After that,propofol infusion rate was adjusted according to the changes of blood pressure and kept at 4 mg?kg-1?h-1 5 min before incision.Blood pressure(BP),heart rate(HR),intubation score(following Grant's method) and all side effects and adjuvant drugs used were recorded. Results Grant scores in all patients were less than 8.Atropine and ephedrine were given more in large dose groups and with decreasing of usage of propofol.HR decreased markedly in 0.3 ?g?kg-1?min-1 group after remifentanil began(P

Changes of IFN-gamma, IL-2, IL-6 and IL-10 in the patient with cardiac surgery under combined acupuncture anesthesia / 中国针灸

<p><b>OBJECTIVE</b>To observe the effect of electroacupuncture (EA) on cytokines in the cardiac surgical patient and to evaluate the application of combined acupuncture anesthesia to cardiac surgery.</p><p><b>METHODS</b>Thirty patients with atrial septal defect were divided into 3 groups, general anesthesia group (A), acupuncture anesthesia group (B) and combined general anesthesia and EA group (C). Peripheral blood samples were collected before anesthesia, before cardiopulmonary bypass (CPB), 30 min after CPB and 24 h after operation to determine the levels of interferon-gamma (IFN-gamma), interleukin-2 (IL-2), IL-6 and IL-10.</p><p><b>RESULTS</b>The levels of IFN-gamma and IL-2 decreased in the 3 groups after CPB and further decreased 24 h after operation, and in the group C were higher than those in the group B. The levels of IL-6 and IL-10 significantly increased 24 h after operation in the 3 groups with no significant difference among the 3 groups.</p><p><b>CONCLUSION</b>The general anesthesia combined with EA can not completely improve the decrease of IFN-gamma and IL-2 induced by CPB, indicating that the good response of the general anesthesia combined with EA to stress can partially improve the immunosupression induced by CPB. Acupuncture does not have significant effect on inflammatory cytokine reaction induced by cardiac surgery.</p>

Effect of acupuncture-drug compound anesthesia on alteration of immune function in patients undergoing open-heart surgery / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the effect of electro-acupuncture (EA) on alteration of immune function of patients undergoing open-heart surgery with cardiopulmonary bypass (CPB), and to appraise the value of acupuncture-drug compound anesthesia in the operation.</p><p><b>METHODS</b>Thirty patients undergoing atrial septal defect repairing operation were selected and divided into three groups, Group A was the general anesthesia group; Group B, the acupuncture anesthesia group and Group C, the general anesthesia plus EA group. Peripheral venous blood of patients was collected at different time points, i.e. before anesthesia, before CPB, 30 min and 24 hrs after CPB, to determine natural killer cells activity (NKCA), and the levels of interferon-gamma (IFN-gamma) and interleukin-2 (IL-2) in supernatant of cell culture were also tested.</p><p><b>RESULTS</b>NKCA was significantly lowered in Group A before CPB but increased in Group B, while no evident change was found in Group C, so the level of NKCA in Group B was significantly higher than in the other two groups. It lowered in all the three groups after CPB, especially evidently in Group B, so as to cause the NKCA level in Group B lower than that in Group A. The lowering further progressed, 24 hrs after CPB, NKCA in Group B was more reduced than that in Group C. Levels of IFN-gamma and IL-2 lowered in all the three groups after CPB, and further lowered at time point of 24 hrs after CPB, but the parameters in Group C were significantly higher than those in Group B.</p><p><b>CONCLUSION</b>EA could enhance NKCA, but acupuncture anesthesia couldn't inhibit the suppressive effect of CPB on NKCA, IL-2 and IFN-gamma, suggesting that the immunosuppression induced by stress has a prior effect. General anesthesia plus EA yielded better effect than general anesthesia and acupuncture anesthesia, but it could't improve the immunosuppression completely, indicating that the compound anesthesia could partially improve the immunosuppression induced by CPB.</p>