The development and progression of CRC are regarded as a complicated network and progressive event including genetic and/or epigenetic alterations. Recent researches revealed that MicroRNAs are ...biomarkers and regulators of CRC progression. Analyses of published microarray datasets revealed that miR-450b-5p was highly up-regulated in CRC tissues. In addition, high expression of miR-450b-5p was significantly associated with KRAS mutation. However, the role of miR-450b-5p in the progression of CRC remains unknown. Here, we sought to validate the expression of miR-450b-5p in CRC tissues and investigate the role and underlying mechanism of miR-450b-5p in the progression of CRC. The results revealed that miR-450b-5p was up-regulated in CRC tissues, high expression level of miR-450b-5p was positively associated with poor differentiation, advanced TNM classification and poor prognosis. Moreover, miR-450b-5p was especially high in KRAS-mutated cell lines and could be up-regulated by KRAS/AP-1 signaling. Functional validation revealed that overexpression of miR-450b-5p promoted cell proliferation and tumor growth while inhibited apoptosis of CRC cells. Furthermore, we demonstrated that miR-450b-5p directly bound the 3'-UTRs of SFRP2 and SIAH1, and activated Wnt/β-Catenin signaling. In conclusion, miR-450b-5p induced by oncogenic KRAS is required for colorectal cancer progression. Collectively, our work helped to understand the precise role of miR-450b-5p in the progression of CRC, and might promote the development of new therapeutic strategies against CRC.
To improve the biocatalytic performance of Candida rugosa lipase (CRL), a CRL-gold nanoparticles (AuNPs) nanobiohybrids was prepared by Methanobactin (Mb)-mediated in situ synthesis of AuNPs. The ...steroselective hydrolysis of (R, S)-Naproxen ester catalyzed by CRL
was chosen as model reaction. Compared with its natural form, the enantioselectivity of CRL have been significantly enhanced by Mb-mediated AuNPs hybridization. FTIR and Fluorescence Spectrum showed that Mb-mediated in situ synthesis of AuNPs could induce the conversion of α-helix
to β-sheet and unfold CRL molecules. The change degree of CRL conformation and its catalytic performance were dependent on the HAuCl4 concentration in hybridization. Compared with natural CRL, the enantiomeric ratio (E) was improved from 50 to 206 and activity remained
almost unchanged under optimal hybridization conditions. Batch reaction proved that the CRL-AuNPs nanobiohybrids exhibited excellent reusability.
► Screening of mixotrophic nutrients for biomass production by C. vulgaris using RSM. ► Glucose, MgSO4, KNO3 and NaCl are the critical mixotrophic nutrients of C. vulgaris. ► Mixotrophic C. vulgaris ...biomass can be used as the raw material for biorefinery.
The design of an optimum and mixotrophic medium for biomass production and biochemical composition biosynthesis by Chlorella vulgaris was attempted by using response surface methodology. Based on the Plackett–Burman design, glucose, MgSO4·7H2O, KNO3 and NaCl were selected from the eleven factors as the most critical mixotrophic nutrients. Subsequently, the selected four factors were investigated by the Box–Behnken design. Results showed that the maximum biomass yield of 4.28g/L was predicted when the concentrations of glucose, MgSO4·7H2O, KNO3 and NaCl were 25g/L, 1.33g/L, 1.30g/L and 3.02g/L, respectively. Verification of the optimization showed that the biomass content of C. vulgaris could be enhanced from 0.24g/L in photoautotrophic SEM and 1.89g/L in unoptimized mixotrophic medium to 4.24g/L giving 17.67-fold and 2.24-fold increase in biomass production, respectively. The biochemical composition of C. vulgaris cultured in optimized mixotrophic medium indicated that the biomass can be used as the raw material for biorefinery.
Lipase-catalyzed transesterification of ethyl ferulate (EF) with triolein (TO), to form ferulyl oleins in a solvent-free medium, was investigated. Water activity (
a
w) had an obvious influence on ...transesterification efficacy. A possible explanation is that the reaction of EF with TO would be deacylation-rate determined. In order to enhance the combined yield of ferulyl diolein (FDO) and ferulyl monoolein (FMO) and minimize hydrolysis of substrate, glycerol (rather than water) was introduced to the reaction. A maximal combined yield of 29.0% of FDO and FMO was obtained using a 1:3 mole ratio of glycerol to TO in solvent-free medium at 60
°C. Compared to the ferulyl olein synthesis conducted by the normal pressure magnetic stirring procedure, the synthesis of ferulyl oleins by a vacuum-rotary evaporation procedure, with a vacuum of 7.5
mmHg, affords higher yields within the same time. The enzyme can be reused several times without significant loss of activity.
PTSA–ZnCl
2 has been proved to be an excellent catalyst for liquid-phase Beckmann rearrangement of ketoximes in acetonitrile. The satisfactory yields of amides were obtained in the presence of this ...catalyst system.
PTSA–ZnCl
2 has been proved to be an excellent catalyst for liquid-phase Beckmann rearrangement of ketoximes in acetonitrile. The satisfactory yields of amides were obtained in the present of this catalyst system.
Highly efficient and environmentally benign intermolecular hydroamination of non-activated olefins with amides and benzyl carbamate catalyzed by silicotungstic acid (HSiW) are described.
...Intermolecular hydroamination of non-activated olefins with amides and benzyl carbamate proceeds efficiently in the presence of environmentally benign silicotungstic acid (HSiW) catalyst under mild conditions in air to afford addition products in good to excellent yields.
One-pot formation of the 1,2,4-triazolo1,5- b pyridazine nucleus and its derivatives is presented in this manuscript, in which the desired targets are offered easily via cooperative Cu( i ) and Zn( ...ii )-catalyzed tandem C–N addition and subsequent I 2 /KI-mediated intramolecular oxidative N–N bond formation.
The transition metal salt-catalyzed direct three-component Mannich reactions of aryl aldehydes, aryl ketones, and carbamates are described. The RuCl3·xH2O-, AuCl3−PPh3-, and AuCl3-catalyzed direct ...Mannich reactions led to the synthesis of N-protected β-aryl-β-amino ketones, and the results create new possibilities for exploiting the transition metal salt-catalyzed direct Mannich reaction and facile synthesis of β-amino ketone libraries.
Background:
Venous thromboembolism (VTE) is highly prevalent in cancer patients. Recent guidelines recommend considering direct oral anticoagulants (DOACs) for the treatment of cancer-associated ...thrombosis (CAT). However, direct head-to-head comparisons among DOACs are lacking, and almost no net clinical benefit (NCB) analysis has been performed in patients with CAT.
Methods:
We systematically searched PubMed, EMBASE, Cochrane Library, and
ClinicalTrials.gov
for randomized controlled trials (RCTs) reporting on recurrent VTE, major bleeding, or clinically relevant bleeding events in patients with CAT who received DOACs and low-molecular-weight heparins. Relative risks (RRs) and 95% confidence intervals (95% CIs) were calculated using a random-effect model. Surface under the cumulative ranking curve (SUCRA) values were calculated, and a trade-off analysis was performed to estimate the NCB.
Results:
Overall, four RCTs involving 2,894 patients were enrolled. DOACs were more effective than dalteparin in reducing the risk of recurrent VTE (RR: 0.62, 95% CI: 0.44–0.87), with a comparative risk of major bleeding (RR: 1.33, 95% CI: 0.84–2.11) and an increased risk of clinically relevant bleeding (RR: 1.45, 95% CI: 1.05–1.99). No significant difference was observed among individual anticoagulants in terms of recurrent VTE and major bleeding. With respect to the ranking of each anticoagulant for the primary outcome, edoxaban (SUCRA: 69.2) was more effective than dalteparin (SUCRA: 60.7), rivaroxaban (SUCRA: 60.7), and apixaban (SUCRA: 25.5) in reducing VTE recurrence. For major bleeding, apixaban (SUCRA: 76.3) had the highest cumulative ranking probability, followed by edoxaban (SUCRA: 66.4), dalteparin (SUCRA: 28.8), and rivaroxaban (SUCRA: 28.5). Similar results were observed for clinically relevant bleeding. In terms of both benefit and safety outcomes, DOACs, especially edoxaban, seemed to confer a better NCB profile than dalteparin.
Conclusions:
DOACs are a safe and effective alternative therapy to dalteparin in patients with CAT. Among them, edoxaban might provide a good risk-to-benefit balance. However, because of the lack of head-to-head studies, further investigations are needed to confirm our findings.
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