Progress on the Prevention of Esophageal Stricture after Endoscopic Submucosal Dissection

Endoscopic submucosal dissection (ESD) has been widely accepted as an effective, minimally invasive treatment for superficial esophageal cancers. However, esophageal stricture often occurs in patients with large mucosal defects after ESD. In this review, we discuss various approaches recently researched to prevent esophageal strictures after ESD. These approaches can be classified as pharmacological treatments, esophageal stent treatments, and tissue engineering approaches. Most of the preventive approaches still have their limitations and require further research. With the improvement of current therapies, ESD can be more widely utilized as a minimally invasive treatment with minimal complications

A Study on the Effect of IL-17A on Phenotypic Transformation of Fibroblasts in Bleomycin-Induced Pulmonary Fibrosis in Mice and Its Mechanism

Objective: In this study, lung fibroblasts were cultured and identified in mice lung fiber model with bleomycin. Under the induction of IL-17A, lung fibroblasts were gradually transformed into myofibroblasts in pulmonary fibrosis, and the specific induction effect of IL-17A in pulmonary fibrosis was analyzed, which could provide ideas for the prevention and treatment of clinical pulmonary fibrosis. Methods: To investigate the transcriptional expression of bleomycin-induced fractional pulmonary fibrosis in different pulmonary fibrosis processes. The 14-day mice model was taken as the research object, and the pulmonary fibrosis model was established by induction of myogenesis. After 14 days of modeling, lung tissue was removed, and after centrifugation and repeated adherent treatment, lung fibroblasts could be cultured at the origin. After three generations of culture, the morphological changes of lung fibroblasts could be observed under a microscope. Indirect immunofluorescence was used to establish the expression of vimentin, and IL-17 was used to stimulate primary cultured lung fibroblasts to detect the expression and specific localization of a-SMA in cells. Western blotting was used to stimulate the expression of lung fibroblast protein by IL-17A at different time points. Results: The typical characteristics of primary culture lung fibroblasts were obtained. After purification and culture, lung fibroblasts were obtained in morphology. The morphology of the 3rd and 4th generation cells was relatively uniform, showing long carboxyform. 1-2 nucleoli can be observed by microscope, which have distinct cell boundary and are lined up like fish schools. The results of indirect immunofluorescence showed that the vimentin staining in the third generation cells was positive, and the plasma was dark red. There were collagenous fibrous septa between the cells, which might make them develop into lung fibroblasts. A-SMA immunofluorescence results showed that in the absence of IL-17A induction, A-SMA signal was relatively weak in the lung fibroblasts of the control group and was in the cytoplasm, while after IL-17A induction, A-SMA signal was stronger in the lung fibroblasts of mice and the whole cells presented spindle structure. Western bletting showed that lung fibroblasts were stimulated by IL-17 in the 0h group. Compared with the 1h, 2h, and 4h groups, the expression of A-SMA in lung fibroblasts was significantly increased in the 1h, 2h, and 4h groups. The fibroblasts were very low in the 2h and 4h groups. There was no significant difference in the expression of AS MA signal. Compared with 0h, protein contents of p-IKB-a and p-p65 were higher in lung fibroblasts at 1h, 2h and 4h. Protein expressions of Acti, 1P6, IKB-a and P65 were different in lung fibroblasts, but there was no significant difference. However, there was no significant statistical difference in the expression of these proteins in lung fibroblasts at different times. Conclusion: By differential centrifugation and repeated adhesion, bleomycin-induced lung fibroblasts can be isolated and purified, and more cell production can be obtained. The staining vimentin was strongly positive after identification by indirect immunofluorescence. The stimulation of IL-17A could gradually transform non-fibroblasts into myofibroblasts and play an important role in pulmonary fibrosis. Therefore, through experimental studies, it was found that IL-17A stimulated F-kB signal and then increased the expression of P-IKB-a and P-P65 proteins, and transformed non-phosphorylated proteins into phosphorylated proteins, thus transforming lung fibroblasts into myofibroblasts and playing a role in pulmonary fibrosis

Advanced Nanostructures for Cell Membrane Poration

Nanostructured devices are able to foster the technology for cell membrane poration. With the size smaller than a cell, nanostructures allow efficient poration on the cell membrane. Emerging nanostructures with various physical transduction have been demonstrated to accommodate effective intracellular delivery. Aside from improving poration and intracellular delivery performance, nanostructured devices also allow for the discovery of novel physiochemical phenomena and the biological response of the cell. This article provides a brief introduction to the principles of nanostructured devices for cell poration and outlines the intracellular delivery capability of the technology. In the future, we envision more exploration on new nanostructure designs and creative applications in biomedical fields.</p

A review of emerging physical transfection methods for CRISPR/Cas9-mediated gene editing

Gene editing is a versatile technique in biomedicine that promotes fundamental research as well as clinical therapy. The development of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) as a genome editing machinery has accelerated the application of gene editing. However, the delivery of CRISPR components often suffers when using conventional transfection methods, such as viral transduction and chemical vectors, due to limited packaging size and inefficiency toward certain cell types. In this review, we discuss physical transfection methods for CRISPR gene editing which can overcome these limitations. We outline different types of physical transfection methods, highlight novel techniques to deliver CRISPR components, and emphasize the role of micro and nanotechnology to improve transfection performance. We present our perspectives on the limitations of current technology and provide insights on the future developments of physical transfection methods

In vitro and ex vivo strategies for intracellular delivery

Intracellular delivery of materials has become a critical component of genome-editing approaches, ex vivo cell-based therapies, and a diversity of fundamental research applications. Limitations of current technologies motivate development of next-generation systems that can deliver a broad variety of cargo to diverse cell types. Here we review in vitro and ex vivo intracellular delivery approaches with a focus on mechanisms, challenges and opportunities. In particular, we emphasize membrane-disruption-based delivery methods and the transformative role of nanotechnology, microfluidics and laboratory-on-chip technology in advancing the field.National Institutes of Health (U.S.) (R01GM101420-01A1

Neurologic Abnormalities in Workers of a 1-Bromopropane Factory

We reported recently that 1-bromopropane (1-BP; n-propylbromide, CAS Registry no. 106-94-5), an alternative to ozone-depleting solvents, is neurotoxic and exhibits reproductive toxicity in rats. The four most recent case reports suggested possible neurotoxicity of 1-BP in workers. The aim of the present study was to establish the neurologic effects of 1-BP in workers and examine the relationship with exposure levels. We surveyed 27 female workers in a 1-BP production factory and compared 23 of them with 23 age-matched workers in a beer factory as controls. The workers were interviewed and examined by neurologic, electrophysiologic, hematologic, biochemical, neurobehavioral, and postural sway tests. 1-BP exposure levels were estimated with passive samplers. Tests with a tuning fork showed diminished vibration sensation of the foot in 15 workers exposed to 1-BP but in none of the controls. 1-BP factory workers showed significantly longer distal latency in the tibial nerve than did the controls but no significant changes in motor nerve conduction velocity. Workers also displayed lower values in sensory nerve conduction velocity in the sural nerve, backward recalled digits, Benton visual memory test scores, pursuit aiming test scores, and five items of the Profile of Mood States (POMS) test (tension, depression, anxiety, fatigue, and confusion) compared with controls matched for age and education. Workers hired after May 1999, who were exposed to 1-BP only (workers hired before 1999 could have also been exposed to 2-BP), showed similar changes in vibration sense, distal latency, Benton test scores, and depression and fatigue in the POMS test. Time-weighted average exposure levels in the workers were 0.34–49.19 ppm. Exposure to 1-BP could adversely affect peripheral nerves or/and the central nervous system

Nurse Participation in Colonoscopy Observation versus the Colonoscopist Alone for Polyp and Adenoma Detection: A Meta-Analysis of Randomized, Controlled Trials

The role of nurse participation (NP) in colonoscopy observation for polyp and adenoma detection is unclear. This study aimed to evaluate whether nurse participation can improve polyp and adenoma detection. Patients and Methods. The PUBMED, EMBASE, and Cochrane Library databases were searched for randomized controlled trials (RCTs) published in English. The outcome measurements included (1) the polyp and adenoma detection rate (PDR and ADR); (2) the advanced lesions detection rate; and (3) the mean polyp and adenoma detection rate per colonoscopy. Results. Three RCTs with a total of 1676 patients were included. The pooled data showed a significantly higher ADR in the NP group than colonoscopist alone (CA) (45.7% versus 39.3%; RR 1.16; 95% CI, 1.04–1.30). And it showed no significant difference in the PDR and advanced lesions detection rate between the two groups (RR: 1.14, 95% CI: 0.95–1.37; RR: 1.35, 95% CI: 0.91–2.00; resp.). Conclusions. Nurse participation during a colonoscopy can improve the ADR, whereas no benefit for the PDR and advanced lesions detection rate was observed. All RCTs included in the meta-analysis had high risk of bias. Thus, there is a need for new research that uses sound methodology to definitively address the research question under study

Pyrimido[4,5‐ d ]pyrimidin‐4(1 H )‐one Derivatives as Selective Inhibitors of EGFR Threonine 790 to Methionine 790 (T790M) Mutants

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/99681/1/8387_ftp.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/99681/2/anie_201302313_sm_miscellaneous_information.pd

On-chip Acousto Thermal Shift Assay for Rapid and Sensitive Assessment of Protein Thermodynamic Stability

In article number 2003506, Xiaoyun Ding and co‐workers present an acousto thermal shift assay (ATSA) utilizing acoustic mechanisms to denature proteins and concentrate protein precipitates for rapid and label‐free assessment of protein thermodynamic changes in real time. The whole process, including sample handling, protein unfolding, and measurement, takes place within a microfluidic chip in less than two minutes, and is faster than other current thermal shift assays.</p