Belamcanda chinensis extract inhibits non-small cell lung cancer proliferation and induces apoptosis via inhibiting the MAPK (Ras/Raf) and Akt pathways.

Non-small cell lung cancer (NSCLC) is associated with high mortality and morbidity rates. Despite major progress of treatment of NSCLC over the past few decades, the prognosis of advanced NSCLC is poor, with 5-year survival rates ranging from 2 % to 13 %. Belamcanda chinensis is a traditional Chinese medicine used to promote blood circulation, reduce swelling, heal ulcers, disperse lumps and tumors, and resolve blood stasis. In the present study, the anti-proliferative and pro-apoptotic effects and potential mechanisms of action of Belamcanda chinensis extract (BCE) in SPC-A1 and NCI-H460 NSCLC cells were investigated using MTS, flow cytometry, and western blotting. Also, xenograft model in vivo was established to investigate the anti-NSCLC effects of BCE. The compounds in BCE were quantified using gas chromatography-mass spectrometry (GC-MS). Twenty compounds were found in BCE, and BCE induced cell cycle arrest significantly inhibited the proliferation of NSCLC. Furthermore, BCE was found to induce Cyto C release and the activation of Caspase-3, -8, -9, PARP, ultimately inducing apoptosis in NSCLC cells through both exogenous and endogenous apoptotic pathways (the mitochondrial pathway). BCE also blocked the MAPK (Ras/Raf) and Akt signaling pathways, significantly downregulating the expression of Ras, Raf, Erk1/2, p-Erk1/2, Akt, and p-Akt proteins. Furthermore, BCE significantly inhibited the growth of NSCLC cells SPC-A1 in nude mice and downregulated Ras, Raf, Akt, and p-Akt expression in vivo. The antitumor effects of BCE suggest its potential clinical application in patients with NSCLC, especially in those bearing Ras or Raf mutations.

Modified Manual Chest Compression for Prevention and Treatment of Respiratory Depression in Patients Under Deep Sedation During Upper Gastrointestinal Endoscopy: Two Randomized Controlled Trials.

BACKGROUND: We aimed to determine the preventive and therapeutic efficacy of modified manual chest compression (MMCC), a novel noninvasive and device-independent method, in reducing oxygen desaturation events in patients undergoing upper gastrointestinal endoscopy under deep sedation. METHODS: A total of 584 outpatients who underwent deep sedation during upper gastrointestinal endoscopy were enrolled. In the preventive cohort, 440 patients were randomized to the MMCC group (patients received MMCC when their eyelash reflex disappeared, M1 group) or control group (C1 group). In the therapeutic cohort, 144 patients with oxygen desaturation of a Sp o2 < 95% were randomized to MMCC group (patients who subsequently received MMCC, M2 group) or the conventional treatment group (C2 group). The primary outcomes were the incidence of desaturation episodes with an Sp o2 < 95% for the preventive cohort and the time spent below 95% Sp o2 for the therapeutic cohort. Secondary outcomes included the incidence of gastroscopy withdrawal and diaphragmatic pause. RESULTS: In the preventive cohort, MMCC reduced the incidence of desaturation episodes <95% (14.4% vs 26.1%; RR, 0.549; 95% confidence interval [CI], 0.37-0.815; P = .002), gastroscopy withdrawal (0% vs 2.29%; P = .008), and diaphragmatic pause at 30 seconds after propofol injection (74.5% vs 88.1%; RR, 0.846; 95% CI, 0.772-0.928; P < .001). In the therapeutic cohort, patients who received MMCC had a significantly shorter time spent below 95% Sp o2 (40 [20-69] seconds vs 91 [33-152] seconds, median difference [95% CI], -39 [-57 to -16] seconds, P < .001), a lower incidence of gastroscopy withdrawal (0% vs 10.4%, P = .018), and more enhanced diaphragmatic movement at 30 seconds after Sp o2 <95% (1.11 [0.93-1.4] cm vs 1.03 [0.7-1.24] cm; median difference [95% confidence interval], 0.16 [0.02-0.32] cm; P = .015). CONCLUSIONS: MMCC may exert preventive and therapeutic effects against oxygen desaturation events during upper gastrointestinal endoscopy.

Cu(II)-Mediated aerobic oxidative synthesis of sulfonated chromeno[4,3-c]pyrazol-4(2H)-ones.

Herein, starting with propiolates and sulfonyl hydrazides, we developed a concise and facile synthesis of 2-sulfonylated chromeno [4,3-c]pyrazol-4(2H)-ones or 2,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-ones via Cu(II)-promoted oxidative cascade C-C/C-N bond formation. This protocol has the advantages of atom economy and good functional group tolerance. The primary mechanism studies indicate that the reaction involves a free-radical process as well as terminal alkyne C-H activation.

Prolonged symptom onset to admission time is associated with severe Coronavirus disease: A meta combined propensity-adjusted analysis.

BACKGROUND: Patients with severe COVID-19 are more likely to develop adverse outcomes with a huge medical burden. We aimed to investigate whether a shorter symptom onset to admission time (SOAT) could improve outcomes of COVID-19 patients. METHODS: A single-center retrospective study combined with a meta-analysis was performed. The meta-analysis identified studies published between 1 December 2019 and 15 April 2020. Additionally, clinical data of COVID-19 patients diagnosed between January 20 and February 20, 2020, at the First Affiliated Hospital of the University of Science and Technology of China were retrospectively analyzed. SOAT and severity of illness in patients with COVID-19 were used as effect measures. The random-effects model was used to analyze the heterogeneity across studies. Propensity score matching was applied to adjust for confounding factors in the retrospective study. Categorical data were compared using Fisher's exact test. We compared the differences in laboratory characteristic varied times using a two-way nonparametric, Scheirer-Ray-Hare test. RESULTS: In a meta-analysis, we found that patients with adverse outcomes had a longer SOAT (I2 = 39%, mean difference 0.88, 95% confidence interval = 0.47-1.30). After adjusting for confounding factors, such as age, complications, and treatment options, the retrospective analysis results also showed that severe patients had longer SOAT (mean difference 1.13 [1.00, 1.27], p = 0.046). Besides, most biochemical marker levels improved as the hospitalization time lengthened without the effect of disease severity or associated treatment (p < 0.001). CONCLUSION: Shortening the SOAT may help reduce the possibility of mild patients with COVID-19 progressing to severe illness.

Detection of glycoprotein through fluorescent boronic acid-based molecularly imprinted polymer.

A novel strategy based on the fluorescent molecularly imprinted polymers (FMIP) for specific recognition and sensitive sensing glycoprotein from biological samples was developed. The FMIP prepared by introducing a fluorescent boronic acid quinoline-based on the PGMA/EDMA bead surface and assembled a glycoprotein molecularly imprinted polymer using surface imprinting technology. The resultant material showed specific recognition to model glycoprotein. At the same time, the change of fluorescence caused by the amount of model glycoprotein could achieve quantitative determination. The method provided a good linear relationship of the concentrations of HRP in the range of 0.05-1 µM, and the detection limit was 0.02 µM. It is 10 times lower than the previous fluorescence nanosensor for glycoprotein. The established method combined the desired selectivity of molecularly imprinted polymers and high sensitivity of fluorescence spectroscopy. The influence of background impurities could be effectively eliminated. The outstanding features guarantee that it can be successfully applied to detect glycoprotein from biological samples under physiological conditions.

Spectroscopic quantification of 5-hydroxymethylcytosine in genomic DNA using boric acid-functionalized nano-microsphere fluorescent probes.

5-hydroxymethylcytosine (5hmC) is the sixth base of DNA. It is involved in active DNA demethylation and can be a marker of diseases such as cancer. In this study, we developed a simple and sensitive 2-(4-boronophenyl)quinoline-4-carboxylic acid modified poly (glycidyl methacrylate (PBAQA-PGMA) fluorescent probe to detect the 5hmC content of genomic DNA based on T4 ß-glucosyltransferase-catalyzed glucosylation of 5hmC. The fluorescence-enhanced intensity recorded from the DNA sample was proportional to its 5-hydroxymethylcytosine content and could be quantified by fluorescence spectrophotometry. The developed probe showed good detection sensitivity and selectivity and a good linear relationship between the fluorescence intensity and the concentration of 5 hmC within a 0-100nM range. Compared with other fluorescence detection methods, this method not only could determine trace amounts of 5 hmC from genomic DNA but also could eliminate the interference of fluorescent dyes and the need for purification. It also could avoid multiple labeling. Because the PBAQA-PGMA probe could enrich the content of glycosyl-5-hydroxymethyl-2-deoxycytidine from a complex ground substance, it will broaden the linear detection range and improve sensitivity. The limit of detection was calculated to be 0.167nM after enrichment. Furthermore, the method was successfully used to detect 5-hydroxymethylcytosine from mouse tissues.

A ratiometric fluorescence RRE RNA-targeted assay for a new fluorescence ligand.

The Rev protein regulates HIV-1 gene expression. Small ligands that bind to the Rev response element (RRE) RNA would inhibit Rev function and suppress HIV-1 replication. A novel ratiometric fluorescence assay was applied in the present study to monitor ligand-RNA interactions by using red-emitting CdTe quantum dots (QDs) coated with silica as a reference. A small fluorescence ligand, ICR 191, was found to interact with RRE at the Rev binding site and compete with the Rev peptide. After adding red-emitting QDs to the interaction system, it was observed that ICR 191 did not fluoresce upon the addition of RRE, and fluorescence recovered when ICR 191 was displaced by a Rev model peptide, whereas the fluorescence of QDs remained constant. Furthermore, variations in the fluorescence ratios between ICR 191 and QDs were exploited to characterize the interactions of Rev with two known antagonists, neomycin B and tobramycin, by using RRE RNA with ICR 191 as a fluorescence indicator. Together, our results demonstrated that ratiometric fluorescence-based nanotechnology applications can be used for ligand-RNA interaction assays. This ICR 191-RRE RNA interaction assay can potentially be developed to build a screening model for assessing antagonists of the Rev binding element in RRE.