Postoperative intermittent pneumatic compression for preventing venous thromboembolism in Chinese lung cancer patients: a randomized clinical trial.

BACKGROUND: Postoperative lung cancer patients belong to the high-risk group for venous thromboembolism (VTE). The standardized preventive measures for perioperative VTE in lung cancer are not perfect, especially for the prevention and treatment of catheter-related thrombosis (CRT) caused by carried central venous catheters (CVCs) in lung cancer surgery. PATIENTS AND METHODS: This study included 460 patients with lung cancer undergoing video-assisted thoracic surgery (VATS) in our center from July 2020 to June 2021. Patients were randomized into two groups, and intraoperatively-placed CVCs would be carried to discharge. During hospitalization, the control group was treated with low-molecular-weight heparin (LMWH), and the experimental group with LMWH + intermittent pneumatic compression (IPC). Vascular ultrasound was performed at three time points which included before surgery, before discharge, and one month after discharge. The incidence of VTE between the two groups was studied by the Log-binomial regression model. RESULTS: CRT occurred in 71.7% of the experimental group and 79.7% of the control group. The multivariate regression showed that the risk of developing CRT in the experimental group was lower than in the control group (Adjusted RR = 0.889 [95%CI0.799-0.989], p = 0.031), with no heterogeneity in subgroups (P for Interaction > 0.05). Moreover, the fibrinogen of patients in the experimental group was lower than control group at follow-up (P = 0.019). CONCLUSION: IPC reduced the incidence of CRT during hospitalization in lung cancer patients after surgery. TRIAL REGISTRATION: No. ChiCTR2000034511.

Effect of miR-630 expression on esophageal cancer cell invasion and migration.

BACKGROUND: Esophageal cancer (EC) is a common malignancy of the digestive tract, with high incidence. The objective of this study was to investigate the effect of miR-630 expression on esophageal cancer (EC) cell invasion and migration. METHODS: The study group comprised 58 EC patients admitted to our hospital from April 2014 to 2016, and the control group comprised 60 healthy people visiting the hospital during the same period. miR-630 levels in the peripheral blood of the two groups were compared, and the diagnostic value of miR-630 for EC was analyzed. EC cell lines were used to evaluate the influence of miR-630 expression on EC cell invasion and migration. RESULTS: miR-630 expression was low in EC (p < 0.050). A receiver operating characteristic curve analysis showed that miR-630 expression had a good diagnostic value for EC (p < 0.050) and was associated with disease course, pathological stage, differentiation degree, tumor metastasis, and patient prognosis and survival (p < 0.05). The ROC curve analysis showed that when cutoff value was 5.38, the diagnostic sensitivity and specificity of miR-630 for EC were 73.33% and 76.67%, respectively; area under the ROC curve was 0.778 (95%CI 0.695-0.861). Transfection of miR-630 into EC cells indicated that miR-630 overexpression can reduce EC cell invasion and migration (p < 0.05). miR-630 expression is low in EC and has good diagnostic value for EC. CONCLUSION: miR-630 overexpression can reduce EC cell invasion and migration, showing a possible key role of miR-630 in EC diagnosis and treatment in the future.

Why ligand cross-reactivity is high within peptide recognition domain families? A case study on human c-Src SH3 domain.

Many important protein-protein interactions in eukaryotic signaling networks are mediated by peptide recognition domains (PRDs), which bind short linear sequence motifs in other proteins. However, high ligand cross-reactivity is observed within most PRD families, rendering a broad specificity for the family members. In the present study, we attempt to explore the molecular mechanism and physicochemical origin of PRD cross-reactivity. In the procedure, a structure-based method called atomic cross-nonbonded interaction analysis (ACNIA) is described to extract atomic-level nonbonded interaction information at domain-peptide interface and to correlate the information with peptide affinity based on a set of structure-solved, affinity-known protein-peptide complex samples compiled from numerous literatures and databases. The ACNIA-derived affinity predictor is tested rigorously with statistical validation approach, which is also demonstrated to be capable of perceiving slight structural change in the interface using three distinct panels of SH3-binding peptide data. Subsequently, with help of the affinity predictor we adopt the human c-Src SH3 domain, one of the most sophisticated PRDs, as a paradigm to investigate the ligand cross-reactivity within SH3 family. It is found that most of the family members have only few non-essential residue differences in their peptide-binding pockets, and thus exhibit a similar peptide recognition profile and high cross-reactivity. The cross-reactivity is even shared by different subclasses of SH3 domains. The findings suggest that inherent binding specificity is not the only factor to select appropriate binders for specific SH3 domains, and other aspects such as cellular context and the rest of the SH3-containing proteins may play important roles in reducing their ligand cross-reactivity.

Toward quantitative characterization of the binding profile between the human amphiphysin-1 SH3 domain and its peptide ligands.

A new structure-based approach was proposed to quantitatively characterize the binding profile of human amphiphysin-1 (hAmph1) SH3 domain-peptide complexes. In this protocol, the protein/peptide atoms were classified into 16 types in terms of their physicochemical meaning and biological function, and then a 16 x 16 atom-pair interaction matrix was constructed to describe 256 atom-pair types between the SH3 domain and the peptide ligand, with atoms from peptide and SH3 domain served as the matrix columns and rows, respectively. Three non-covalent effects dominating SH3 domain-peptide binding as electrostatic, van der Waals (steric) and hydrophobic interactions were separately calculated for the 256 atom-pair types. As a result, 768 descriptors coding detailed information about SH3 domain-peptide interactions were yielded for further statistical modeling and analysis. Based on a culled data set consisting of 592 samples with known affinities, we employed this approach, coupled with partial least square (PLS) regression and genetic algorithm (GA), to predict and to interpret the peptide-binding behavior to SH3 domain. In comparison with the previous works, our method is more capable of capturing important factors in the SH3 domain-peptide binding, thus, yielding models with better statistical performance. Furthermore, the optimal GA/PLS model indicates that the electrostatic effect plays a crucial role in SH3 domain-peptide complexes, and steric contact and hydrophobic force also contribute significantly to the binding.

Co-expression of Rho guanine nucleotide exchange factor 5 and Src associates with poor prognosis of patients with resected non-small cell lung cancer.

Specific and sensitive enough molecular biomarkers are lacking to accurately predict the survival of non-small cell lung cancer (NSCLC) patients. ARHGEF5 and Src have been shown to play an important role in tumorigenesis. However, the involvement of ARHGEF5 and Src in NSCLC remains unknown. Therefore, we evaluated the expression of ARHGEF5 and Src in resected NSCLC tissues and the correlation of co-expression of ARHGEF5 and Src and the prognosis of patients with resected NSCLC. Positive expression of ARHGEF5 was detected in 133 cases of 193 patients (68.91%). A total of 193 NSCLC patients (male: 145; female: 48; average age: 61.84 years; age range: 31-84) were enrolled in this study, of which 99 cases were squamous cell carcinomas (SCCs) (51.30%) and 94 cases were adenocarcinomas (ADCs) (48.70%). The expression of ARHGEF5 was mainly located in the cytoplasm of tumor cells, but not in the corresponding adjacent lung tissues. The levels of ARHGEF5 were significantly associated with age, differentiation and tumor stage. ARHGEF5 protein expression was associated with Src protein expression in NSCLC (χ(2) = 11.874, P<0.01) and in ADC (χ(2) = 12.194, P<0.01), but not in SCC. Co-immunoprecipitation revealed that there was a physical interaction between Src and ARHGEF5 in lung cancer cells. The patients with ARHGEF5(+)/Src(+) had a shorter survival time compared with the other patients (29.37 months versus 39.90 months, P = 0.029). In conclusion, ARHGEF5/Src can be considered as a prognostic biomarker and a therapeutic target for patients with resected NSCLC.

Exploring the activity space of peptides binding to diverse SH3 domains using principal property descriptors derived from amino acid rotamers.

Although there were intensive works addressed on multivariate extraction of the informative components from numerous physicochemical parameters of amino acids in isolated state, the various conformational behaviors of amino acids in complicated biological context have long been underappreciated in the field of quantitative structure-activity relationship (QSAR). In this work, the amino acid rotamers, which were derived from statistical survey of protein crystal structures, were used to reproduce the conformational variety of amino acid side-chains in real condition. In this procedure, these rotamers were superposed into a nx x ny x nz lattice and an artificial probe was employed to detect four kinds of nonbonding field potentials (i.e., electrostatic, steric, hydrophobic, and hydrogen bonds) at each lattice point using a Gaussian-type potential function; the generated massive data were then subjected to a principal component analysis (PCA) treatment to obtain a set of few, informative amino acid descriptors. We used this set of descriptors, that we named principal property descriptors derived from amino acid rotamers (PDAR), to characterize over 13,000 peptides with known binding affinities to 10 types of SH3 domains. Genetic algorithm/ partial least square regression (GA/PLS) modeling and Monte Carlo cross-validation (MCCV) demonstrated that the correlation between the PDAR descriptors and the binding affinities of peptides are comparable with or even better than previously published models. Furthermore, from the PDAR-based QSAR models we concluded that the core motif of peptides, particularly the electrostatic property, hydrophobicity, and hydrogen bond at residue positions P3, P2, and/or P0, contribute significantly to the hAmph SH3 domain-peptide binding, whereas two ends of the peptides, such as P6, P4, P-4, and P5, only play a secondary role in the binding.

Nanosilver-doped DNA polyion complex membrane for electrochemical immunoassay of carcinoembryonic antigen using nanogold-labeled secondary antibodies.

A simple and sensitive electrochemical immunoassay protocol was developed for the detection of carcinoembryonic antigen (CEA) using nanosilver-doped DNA polyion complex membrane (PIC) as sensing interface. To construct such an immunosensor, double-stranded DNA was initially assembled onto the surface of thionine/Nafion-modified screen-printed carbon electrode to adsorb silver ions with positive charges, then silver ions were reduced to nanosilver particles with the aid of NaBH(4), and then anti-CEA antibodies were immobilized on the nanosilver surface. Gold nanoparticles conjugated with horseradish peroxidase-labeled anti-CEA were employed as signal antibodies for the detection of CEA with a sandwich-type assay format. Under optimal conditions, the immunosensor exhibited a dynamic range of 0.03-32 ng mL(-1) with a low detection limit of 10 pg mL(-1) CEA. Intra- and inter-assay imprecision (CVs) were <9.5% and 6.5%, respectively. The response could remain 90.1% of the original current at 30th day. 50 real samples were evaluated using the immunosensor and the enzyme-linked immunosorbent assay, respectively, and received in accordance with those two methods.