Intestinal topical lidocaine spray improves the efficacy and safety of endoscopic sigmoid polypectomy.

BACKGROUND AND AIMS: Endoscopic polypectomy can prevent colorectal cancer. Adequate surgical field visualization is crucial to complete resection. To prevent visual field loss caused by intestinal peristalsis, we investigated the efficacy and safety of topical lidocaine spraying during the endoscopic sigmoid polypectomy (ESP). METHODS: Retrospective analysis was performed on 100 ESP patients admitted from July 2021 to October 2021, among which 50 patients received lidocaine (case group) and other 50 patients received normal saline (control group). Lidocaine or saline was sprayed on the colonic mucosa within 5 cm above and below the polyps before polypectomy. The en-bloc resection rate (EBRR) and complete resection rate (CRR) were primarily evaluated. Secondary outcomes included EBRR for polyps located in the 5-11 o'clock position, sigmoid colon peristalsis frequency, degree of exposure to the surgical field, operative times, and adverse events. RESULTS: There were no significant differences in the basic demographic characteristics between the two groups. EBRR and CRR in the case group were 72.9% and 95.8%, and in the control group were 53.3% and 91.1%, respectively. The EBRR of sigmoid polyps located at the 5-11 o'clock positions was significantly higher in the case group (82.8%) than in the control group (56.7%) (P = 0.03). Sigmoid colonic peristalsis was significantly inhibited after lidocaine spraying (P < 0.01). There was no statistical difference in the operative times and adverse event rates between the two groups. CONCLUSION: Topical spraying lidocaine around polyps can safely and effectively reduce intestinal peristalsis, thus improving the EBRR of sigmoid polypectomy.

MicroRNA-19a promotes proliferative and migratory abilities of NSCLC cells by inhibiting PTEN expression.

PURPOSE: To investigate whether microRNA-19a can promote the proliferative and migratory abilities of non-small cell lung cancer (NSCLC) cells by target inhibition of PTEN (phosphatase and tensin homolog deleted from chromosome 10, PTEN) expression, thus leading to the development of NSCLC. METHODS: The expression level of microRNA-19a in NSCLC tissues, paracancerous tissues and normal lung tissues was detected by quantitative real time-polymerase chain reaction (qRT-PCR). The regulatory effects of microRNA-19a on proliferative and migratory abilities of NSCLC cells were determined by cell counting kit-8 (CCK-8), colony formation assay and Transwell assay, respectively. The binding condition between microRNA-19a and PTEN was verified by dual-luciferase reporter gene assay. PTEN expression in NSCLC cells transfected with microRNA-19a mimic or inhibitor was detected by Western blot. Rescue experiments were conducted by co-transfection of microRNA-19a mimic and pcDNA-PTEN in NSCLC cells, followed by detection of cell proliferation, colony formation and migration. RESULTS: QRT-PCR data showed higher expression of microRNA-19a in NSCLC tissues and cell lines than that of controls. Overexpression of microRNA-19a in NSCLC A549 and H1299 cell lines promoted proliferative and migratory abilities. Dual-luciferase reporter gene assay confirmed the binding site between microRNA-19a and PTEN. PTEN expression was negatively regulated by microRNA-19a both at mRNA and protein levels. Rescue experiments showed that PTEN overexpression could partially reverse the regulatory effects of microRNA-19a on promoting proliferative and migratory abilities of NSCLC cells. CONCLUSIONS: Higher expression of microRNA-19a promotes proliferative and migratory abilities of NSCLC cells by target inhibiting PTEN expression.

Labeling of Microthrix parvicella in situ: A novel FRET probe based on bisoctyl rhodamine B.

Filamentous bacteria, particularly Microthrix parvicella, are mainly responsible for bulking or foaming of activated sludge. Based on the affinity of M. parvicella to the hydrophobic characteristics of long-chain fatty acids, a novel bisoctyl rhodamine B (BORB) and a novel fluorescence resonance energy transfer (FRET) complex probe were prepared herein to study their properties. When the FRET probe was used in in situ activated sludge, M. parvicella was clearly labeled at 20 nmol/L, which was a reduction of 50 times compared to that of the BORB (1 µmol/L) alone and 500 times compared to the carbazole-quinoline probe reported previously. Compared with fluorescence in situ hybridization, M. parvicella could be clearly labeled using BORB and the FRET probe in situ without requiring complicated pretreatments (i.e., shock and broken process, fixed sample, digestion, and lysozyme treatment). This study discusses the facile approach developed for labeling M. parvicella in early warning expansion, thereby inhibiting and controlling sludge bulking in situ.

A light-up probe targeting for Bcl-2 2345 G-quadruplex DNA with carbazole TO.

As its significant role, the selective recognition of G-quadruplex with specific structures and functions is important in biological and medicinal chemistry. Carbazole derivatives have been reported as a kind of fluorescent probe with many excellent optical properties. In the present study, the fluorescence of the dye (carbazole TO) increased almost 70 fold in the presence of bcl-2 2345 G4 compared to that alone in aqueous buffer condition with almost no fluorescence and 10-30 fold than those in the presence of other DNAs. The binding study results by activity inhibition of G4/Hemin peroxidase experiment, NMR titration and molecular docking simulation showed the high affinity and selectivity to bcl-2 2345 G4 arises from its end-stacking interaction with G-quartet. It is said that a facile approach with excellent sensitive, good selectivity and quick response for bcl-2 2345 G-quadruplex was developed and may be used for antitumor recognition or antitumor agents.

A novel fluorescent long-chain fatty acid-substituted dye: labeling and biodegrading of Microthrix parvicella.

Microthrix parvicella (M. parvicella) is a filamentous bacterium that induces bulking in activated sludge. Here, we used the affinity of long-chain fatty acids (LCFA) for M. parvicella to create a novel fluorescent probe of carbazole modified by LCFA. The structure was characterized by 1H NMR spectroscopy and mass spectrometry. The spectral properties, photostability, and hydrophobic properties of the probe were also characterized. Fluorescent-labeling results showed that it can label M. parvicella in situ and could be biodegraded via metabolism. The stable docking mode of carbazole probes with different fatty acid chains and lipases was also docked by the density functional tight-binding (DFTB) method.

[Placenta-derived mesenchymal stem cells with HLA-G positive expression induce Treg in vitro].

OBJECTIVE: To study placenta-derived mesenchymal stem cells with HLA-G (Human Leukocyte Antigen, HLA-G) positive expression induce Treg (regulatory T cell, Treg) in vitro. METHODS: placenta-derived mesenchymal stem cells were separated from neonatal placenta; PEGFP - N1 -HLA-G plasmid was transfected in placenta-derived mesenchymal stem cells by liposome transfection.The cells were divided into 3 groups including control group, PEGFP-N1 group and PEGFP-N1-HLA-G group, 5 complex walls in each group. Expression of HLA-G protein was detected by Western Blotting; after identification of cells, healthy human peripheral blood CD4+ T lymphocytes were cultured with placenta-derived mesenchymal stem cells with HLA-G positive expression, and the ratio of CD4+CD25+Foxp3+Treg in T lymphocytes was accounted. RESULTS: After transfection of PEGFP-N1-HLA-G, the placenta-derived mesenchymal stem cells can express HLA-G protein significantly, compared with the control group and PEGFP - N1 group (P<0.01). After HLA-G positive placenta-derived mesenchymal stem cells and CD4 + T lymphocytes were cultured for 24 h, the ratio of CD4+CD25+Foxp3+Treg in T lymphocytes was (16.41±0.94)%. After HLA - G positive placenta-derived mesenchymal stem cells and CD4+ T lymphocytes were cultured for 48 h, the ratio of CD4+CD25+Foxp3+Treg in T lymphocytes was (16.46±0.59)% significantly, compared with the control group and PEGFP - N1 group (P<0.01). CONCLUSIONS: Placenta-derived mesenchymal stem cells modified by HLA-G gene can effectively induce CD4+CD25+Foxp3+Treg in vitro.

Design Mechanism and Property of the Novel Fluorescent Probes for the Identification of Microthrix Parvicella In Situ.

In this study, two novel fluorescent probes, probe A and probe B were designed, synthesized and characterized, based on Microthrix parvicella (M. parvicella) preferring to utilize long-chain fatty acid (LCFA), for the labeling of M. parvicella in activated sludge. The molecular structure of probe A and probe B include long-chain alkane and LCFA, respectively. The results indicated that probe A and probe B had a large stokes shift of 118 nm and 120 nm and high quantum yield of 0.1043 and 0.1058, respectively, which were significantly helpful for the fluorescent labeling. As probe A was more stable than probe B in activated sludge, and the fluorescence intensity keep stable during 24 h, probe A was more suitable for labeling M. parvicella in situ. In addition, through the Image Pro Plus 6 (IPP 6) analysis, a quantitative relationship was established between sludge volume index (SVI) and integral optical density (IOD) of the labeled M. parvicella in activated sludge samples. The relationship between IOD and SVI conforms to Logistic curve (R² = 0.94).

A large stokes-shifted fluorescent dye synthesized as a new probe for the determination of protein.

A novel fluorescent dye, 1-(2-hydroxyethyl)-4-((E)-2-(3-benzothiazol-2yl-9-ethyl-carbazole-3yl)vinyl) pyridinium bromide, was synthesized for determination of protein and its structure was characterized by (1)H NMR. Photophysics of the new probe in different solvents has been delineated in this paper, the new fluorescent molecular dye exhibited a large stokes-shifted and fluorescence quantum yields in organic solvent. The photostability and thermostability of the new dye were also studied and the results suggested the stable was excellent. The interactions of the dye with bovine serum albumin (BSA) , Human serumal bumin (HSA) and calf thymus deoxyribonucleic acid (ctDNA) were studied by fluorescence and absorption spectroscopy. The binding constant for BSA, HSA and DNA were calculated to be 8.91 × 10(7), 1.86 × 10(6) and 2.9 × 10(4), respectively. The experimental results indicated a potential value of the new dye for biomarker.

Properties, theoretical study and crystal structure of 3-benzothiazole-9-ethyl carbazole.

The title compound of 3-benzothiazole-9-ethyl carbazole was synthesized by the reaction of 3-aldehyde-9-ethyl carbazole and 2-aminothiophenol. The compound was characterized by (1) H nuclear magnetic resonance (NMR) and mass spectrometry (MS). Its crystal structure was obtained and determined by single crystal X-ray diffraction. The results showed that the crystal belongs to the orthorhombic crystal system and the cell parameters of space group P2(1)2(1)2(1) were a = 5.6626 (12) Å, b = 12.606 (3) Å, c = 22.639 (5) Å, α = 90°, ß = 90°, γ = 90°, V = 1616.0 (6) Å(3) , Z = 4, Dc = 1.350 mg/m(3) . The UV-vis and fluorescence spectra were also studied preliminarily. The fluorescence spectra of the title compound with bovine serum albumin (BSA) showed that BSA could be marked with the compound and the stability constant between them was 0.82 × 10(7)  M(-1) . Meanwhile, the crystal and molecule were theoretically surveyed by density functional tight-binding (DFTB). The results showed that there was an orbital overlap for lowest unoccupied molecular orbital (LUMO) between the neighbouring molecules for the crystal, which is different from the molecule structure. It was also showed that the crystal structure is a non-conductor. Copyright © 2016 John Wiley & Sons, Ltd.

Spectra, stability and labeling of 1-(5-carboxypentyl)-4-(2-(N-ethyl-carbazole-3-yl) vinyl) pyridinium bromide with a large Stokes shift.

Carbazole and its derivatives have been widely utilized as a functional building block in the fabrication of the organic medicine, pesticides, materials, etc., because of their excellent solubility, stability and biological activity. In this paper, 1-(5-carboxypentyl)-4-(2-(N-ethyl-carbazole-3-yl) vinyl) pyridinium bromide with a large Stokes shift was synthesized and characterized by (1)H NMR and MS. The UV/vis absorption and fluorescence spectra in different solvents and at different pH values were investigated preliminarily. The photostability and thermostability were also studied and the results showed that the compound was stable. The compound was also used to label bovine serum albumin (BSA) and calf thymus (ct)DNA. The results showed that the fluorescence intensity is enhanced when labeling with BSA and the binding ability is stronger than ctDNA, making it may be used as a biological probe.

Synthesis and characterization of the fluorescent probes for the labeling of Microthrix parvicella.

Although the fluorescent in situ hybridization (FISH) has been widely used to identify the Microthrix parvicella (M. parvicella), there are a few disadvantages and difficulties, such as complicated process, time consuming, etc. In this work, a series of fluorescent probes, which were modified by long-chain alkane with hydrophobic property and based on the property of M. parvicella utilizing long-chain fatty acids (LCFA), for the labeling of M. parvicella in bulking sludge were designed, synthesized, and characterized. The probes were characterized by ultraviolet-visible (UV-Vis) absorption spectra, fluorescence spectra, (1)H NMR spectra, and mass spectra, and the photostability and hydrophobic property of probes were investigated. All the results showed that the probes were quite stable and suitable for the fluorescent labeling. The probes had a large stoke shift of 98-137 nm, which was benefit for the fluorescent labeling. In the fluorescent labeling of M. parvicella by the synthesized probes, the probes had excellent labeling effects. By comparison of the images and the Image Pro Plus 6.0 analysis, the optimal concentration of the probes in the activated sludge sample for labeling was 0.010 mmol/L and the probe 3d had the best labeling. In addition, the effect of the duration time of probes was also investigated, and the results showed that the fluorescent intensity of probes hardly changed in a long period of time and it was suitable for labeling.

Design and preparation of quantum dots fluorescent probes for in situ identification of Microthrix parvicella in bulking sludge.

A series of quantum dots (QDs) fluorescent probes for the in situ identification of Microthrix parvicella (M. parvicella) in bulking sludge were designed and prepared. In the preparation of CdTe/CdS QDs, the 11-mercaptoundecanoic acid (11-acid) and 16-mercaptohexadecanoic acid (16-acid) were used as the stabilizer. The prepared QDs probes were characterized by Fourier transform infrared (FT-IR), X-ray diffraction (XRD), and transmission electron microscopy (TEM), and the results showed that the CdTe/CdS QDs formed a core-shell structure and the long carbon chain was successfully grafted onto its surface. And the three QDs probes had different crystallinity and particle size, which was due to the inhibition effect of long carbon chain. The optical properties test results showed that although the formed core-shell structure and long carbon chain affected the fluorescent intensity, adsorption, and emission spectra of the QDs probes, the probes B and C had a large stokes-shift of 82 and 101 nm, which was a benefit for their fluorescent labeling property. In the fluorescent identification of M. parvicella, the probes B and C effectively adsorbed onto the surface of M. parvicella through a hydrophobic bond, and then identified M. parvicella by their unique fluorescence. In addition, it was found that a better hydrophobic property resulted in better identification efficiency.

A benzindole substituted carbazole cyanine dye: a novel targeting fluorescent probe for parallel c-myc G-quadruplexes.

Many organic ligands were synthesized to recognize G-quadruplexes. However, different kinds of G-quadruplexes (G4s) possess different structures and functions. Therefore, selective recognition of certain types of G4s is important for the study of G4s. In this paper, a novel cyanine dye, 3-(2-(4-vinylpyridine))-6-(2-((1-(4-sulfobutyl))-3,3-dimethyl-2-vinylbenz[e]indole)-9-ethyl-carbazole (9E PBIC), composed of benzindole and carbazole was designed and synthesised. The studies on UV-vis and fluorescence properties of the dye with different DNA forms showed that the dye exhibits almost no fluorescence under aqueous buffer conditions, but it increased over 100 fold in the presence of c-myc G4 and 10-30 fold in the presence of other G4s, while little in the presence of single/double-stranded DNA, indicating that it has excellent selectivity to c-myc 2345 G4. For the binding studies the dye is interacted with the c-myc 2345 G-quadruplex by using the end-stack binding model. It can be said that the dye is an excellent targeting fluorescent probe for c-myc G-quadruplexes.

Spectra, Stability and Labeling of a Novel Carbazole Derivative as a Fluorescent Turn-on DNA Probe.

A novel fluorescent dye, 1-(6-carboxyhexyl)-4-(2-(9-ethyl-carbazole-3-yl) vinyl) quinolizinium bromide, was synthesized, and its structure was characterized by (1)H NMR, (13)C-NMR, IR and HRMS. The spectra properties of this dye in different solvents and under different pH value were invest'igated preliminarily, and the results showed that its fluorescent properties was affected by the polarity and the dipole moment of the solvent. The photostability and thermostability test results showed that its photoreduction rate constant was 1.64 × 10(-5) mol/Min and its fluorescent intensity decreased little after heating at 80 °C for 6 h, suggesting the dye was quite stable. In the labeling experiment of BSA and DNA with the dye, the fluorescent all intensity increased with the addition of BSA and DNA. Specially, the dye showed an excellent turn-on effect upon binding with ctDNA.

Discovery and in vivo evaluation of novel RGD-modified lipid-polymer hybrid nanoparticles for targeted drug delivery.

In the current study, the lipid-shell and polymer-core hybrid nanoparticles (lpNPs) modified by Arg-Gly-Asp(RGD) peptide, loaded with curcumin (Cur), were developed by emulsification-solvent volatilization method. The RGD-modified hybrid nanoparticles (RGD-lpNPs) could overcome the poor water solubility of Cur to meet the requirement of intravenous administration and tumor active targeting. The obtained optimal RGD-lpNPs, composed of PLGA (poly(lactic-co-glycolic acid))-mPEG (methoxyl poly(ethylene- glycol)), RGD-polyethylene glycol (PEG)-cholesterol (Chol) copolymers and lipids, had good entrapment efficiency, submicron size and negatively neutral surface charge. The core-shell structure of RGD-lpNPs was verified by TEM. Cytotoxicity analysis demonstrated that the RGD-lpNPs encapsulated Cur retained potent anti-tumor effects. Flow cytometry analysis revealed the cellular uptake of Cur encapsulated in the RGD-lpNPs was increased for human umbilical vein endothelial cells (HUVEC). Furthermore, Cur loaded RGD-lpNPs were more effective in inhibiting tumor growth in a subcutaneous B16 melanoma tumor model. The results of immunofluorescent and immunohistochemical studies by Cur loaded RGD-lpNPs therapies indicated that more apoptotic cells, fewer microvessels, and fewer proliferation-positive cells were observed. In conclusion, RGD-lpNPs encapsulating Cur were developed with enhanced anti-tumor activity in melanoma, and Cur loaded RGD-lpNPs represent an excellent tumor targeted formulation of Cur which might be an attractive candidate for cancer therapy.

tert-Butyl 4-({[(E)-1,3-dimethyl-5-phen-oxy-pyrazol-4-yl]meth-yl}amino-oxymeth-yl)benzoate.

The title compound, C(24)H(27)N(3)O(4), also known as fenpyroximate, is a commercial acaricide. The benzene ring of the phen-oxy group is approximately perpendicular to the pyrazole ring with a dihedral angle of 84.37 (11)°. The dihedral angle between the phen-oxy and the benzoate benzene rings is 48.83 (8)°.