Publications by authors named "Yu-Li Wang"

91 Publications

The Efficacy of Long-Term Chinese Herbal Medicine Use on Lung Cancer Survival Time: A Retrospective Two-Center Cohort Study with Propensity Score Matching.

Evid Based Complement Alternat Med 2021 23;2021:5522934. Epub 2021 Aug 23.

Department of Oncology, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Objective: To explore the efficacy of long-term use of Chinese herbal medicine (CHM) on survival time of lung cancer.

Methods: We conducted a retrospective cohort study on lung cancer patients. A propensity score matching (PSM) was performed to balance the covariates. Progression-free survival (PFS) was the primary endpoint and overall survival (OS) was the secondary endpoint. Patients who received CHM therapy from the initial date of diagnosis of lung cancer were included in the CHM group. Patients who were not treated with CHM during the same interval were categorized in the control group. A Cox regression model was used to explore the prognostic factors related to lung cancer. Hazard ratios of different subgroups were also analyzed.

Results: A total of 1134 patients were included in our study: 761 patients were in the CHM group and 373 patients were in the control group. After PSM, the mPFS and mOS in the CHM group were 70.4 months and 129.1 months, respectively, while the mPFS and mOS in the control group were 23.8 months and 99.7 months, respectively. The results of survival analysis on each stage demonstrated that patients may benefit from the long-term CHM treatment especially for patients with early stage. One-year to ten-year progression-free survival rates in the CHM group were higher than those in the control group ( < 0.001). COX multivariate regression analysis indicated that CHM treatment, female, low age at diagnosis, early tumor stage, and surgery were independent protective factors against recurrence and metastasis of lung cancer. Subgroup analysis showed that CHM treatment could reduce the risk of recurrence and metastasis in each subgroup ( < 0.01).

Conclusion: Long-term CHM treatment with the which can be flexibly applied in the course of lung cancer treatment, not only has a positive influence on the progression-free survival time of lung cancer patients, but also reduces the risk of recurrence and metastasis of lung cancer.
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http://dx.doi.org/10.1155/2021/5522934DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8407994PMC
August 2021

Novel approaches to intervene gut microbiota in the treatment of chronic liver diseases.

FASEB J 2021 Oct;35(10):e21871

MOE/NHC/CAMS Key Laboratory of Medical Molecular Virology, Department of Medical Microbiology & Parasitology, School of Basic Medical Sciences, Fudan University Shanghai Medical College, Shanghai, China.

Recent investigations of gut microbiota have contributed to understanding of the critical role of microbial community in pathophysiology. Dysbiosis not only causes disturbance directly to the gastrointestinal tract but also affects the liver through gut-liver axis. Various types of dysbiosis have been documented in alcoholic liver disease (ALD), nonalcoholic fatty liver disease, autoimmune hepatitis (AIH), primary sclerosing cholangitis, and may be crucial for the initiation, progression, or deterioration to end-stage liver disease. A few microbial species have been identified as the causal factors leading to these chronic illnesses that either do not have clear etiologies or lack effective treatment. Notably, cytolysin-producing Enterococcus faecalis, Klebsiella pneumoniae and Enterococcus gallinarum were defined for ALD, NASH, and AIH, respectively. These groundbreaking discoveries drive a rapid development in innovative therapeutics, such as fecal microbial transplantation and implementation of specific bacteriophages in addition to prebiotics, probiotics, or synbiotics for intervention of dysbiosis. Although most emerging interventions are in preclinical development or early clinical trials, a better delineation of specific dysbiosis in these disorders at metabolic, immunogenic, or molecular levels in establishing particular causal effects aids in modulating or correcting the microbial community which is the part of daily life for human being.
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http://dx.doi.org/10.1096/fj.202100939RDOI Listing
October 2021

Baseline left ventricular ejection fraction associated with symptom improvements in both children and adolescents with postural tachycardia syndrome under metoprolol therapy.

Chin Med J (Engl) 2021 08 12;134(16):1977-1982. Epub 2021 Aug 12.

Department of Pediatrics, Peking University First Hospital, Beijing 100034, China.

Background: Postural tachycardia syndrome (POTS) is a common childhood disease that seriously affects the patient's physical and mental health. This study aimed to investigate whether pre-treatment baseline left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) values were associated with symptom improvement after metoprolol therapy for children and adolescents with POTS.

Methods: This retrospective study evaluated 51 children and adolescents with POTS who received metoprolol therapy at the Peking University First Hospital between November 2010 and July 2019. All patients had completed a standing test or basic head-up tilt test and cardiac echocardiography before treatment. Treatment response was evaluated 3 months after starting metoprolol therapy. The pre-treatment baseline LVEF and LVFS values were evaluated for correlations with decreases in the symptom score after treatment (ΔSS). Multivariable analysis was performed using factors with a P value of <0.100 in the univariate analyses and the demographic characteristics.

Results: A comparison of responders and non-responders revealed no significant differences in demographic, hemodynamic characteristics, and urine specific gravity (all P > 0.050). However, responders had significantly higher baseline LVEF (71.09% ± 4.44% vs. 67.17% ± 4.88%, t = -2.789, P = 0.008) and LVFS values (40.00 [38.00, 42.00]% vs. 36.79% ± 4.11%, Z = -2.542, P = 0.010) than the non-responders. The baseline LVEF and LVFS were positively correlated with ΔSS (r = 0.378, P = 0.006; r = 0.363, P = 0.009), respectively. Logistic regression analysis revealed that LVEF was independently associated with the response to metoprolol therapy in children and adolescents with POTS (odds ratio: 1.201, 95% confidence interval: 1.039-1.387, P = 0.013).

Conclusions: Pre-treatment baseline LVEF was associated with symptom improvement after metoprolol treatment for children and adolescents with POTS.
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http://dx.doi.org/10.1097/CM9.0000000000001698DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8382470PMC
August 2021

Cyclic stretching-induced epithelial cell reorientation is driven by microtubule-modulated transverse extension during the relaxation phase.

Sci Rep 2021 Jul 20;11(1):14803. Epub 2021 Jul 20.

Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, PA, 15213, USA.

Many types of adherent cells are known to reorient upon uniaxial cyclic stretching perpendicularly to the direction of stretching to facilitate such important events as wound healing, angiogenesis, and morphogenesis. While this phenomenon has been documented for decades, the underlying mechanism remains poorly understood. Using an on-stage stretching device that allowed programmable stretching with synchronized imaging, we found that the reorientation of NRK epithelial cells took place primarily during the relaxation phase when cells underwent rapid global retraction followed by extension transverse to the direction of stretching. Inhibition of myosin II caused cells to orient along the direction of stretching, whereas disassembly of microtubules enhanced transverse reorientation. Our results indicate distinct roles of stretching and relaxation in cell reorientation and implicate a role of myosin II-dependent contraction via a microtubule-modulated mechanism. The importance of relaxation phase also explains the difference between the responses to cyclic and static stretching.
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http://dx.doi.org/10.1038/s41598-021-93987-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8292395PMC
July 2021

Traction force microscopy by deep learning.

Biophys J 2021 08 30;120(15):3079-3090. Epub 2021 Jun 30.

Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, Pennsylvania.

Cells interact mechanically with their surroundings by exerting and sensing forces. Traction force microscopy (TFM), purported to map cell-generated forces or stresses, represents an important tool that has powered the rapid advances in mechanobiology. However, to solve the ill-posed mathematical problem, conventional TFM involved compromises in accuracy and/or resolution. Here, we applied neural network-based deep learning as an alternative approach for TFM. We modified a neural network designed for image processing to predict the vector field of stress from displacements. Furthermore, we adapted a mathematical model for cell migration to generate large sets of simulated stresses and displacements for training and testing the neural network. We found that deep learning-based TFM yielded results that resemble those using conventional TFM but at a higher accuracy than several conventional implementations tested. In addition, a trained neural network is appliable to a wide range of conditions, including cell size, shape, substrate stiffness, and traction output. The performance of deep learning-based TFM makes it an appealing alternative to conventional methods for characterizing mechanical interactions between adherent cells and the environment.
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http://dx.doi.org/10.1016/j.bpj.2021.06.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8390964PMC
August 2021

Optical system for monitoring groundwater pressure and temperature using fiber Bragg gratings.

Opt Express 2021 May;29(11):16032-16045

A depth-discrete groundwater monitoring well is crucial to observing groundwater contamination and subsurface environments. To address this issue, we developed a multilevel monitoring system (MLMS). Because optical fiber sensors are small, have low voltage requirements, and have minimal signal loss over a long distance, we used fiber Bragg grating (FBG) technology to develop a MLMS to observe the depth-discrete aquifer status. The developed FBG sensors and MLMS were examined by a laboratory test and two field tests, respectively. The results show that the FBG piezometer and thermometer accuracies are 0.2% and 0.4% full-scale, respectively. The MLMS can be easily installed in a 2-inch well without a sealing process and can successfully measure the depth-discrete aquifer status at the selected fully-penetrated wells during the two injection events at the study site. The analysis of the collected data and their corresponding injection event reveals the possible structure of the subsurface hydraulic connections at the study sites. These results demonstrate that the FBG MLMS can be an alternative subsurface monitoring system, which has the advantage of a relatively low cost, good data collection efficiency, and environmental sustainability.
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http://dx.doi.org/10.1364/OE.412518DOI Listing
May 2021

CT-guided preoperative localization of ground glass nodule: comparison between the application of embolization microcoil and the locating needle designed for pulmonary nodules.

Br J Radiol 2021 Jul 16;94(1123):20210193. Epub 2021 Jun 16.

Department of Radiology, China-Japan Friendship Hospital, Beijing, China.

Objectives: To compare the efficacy and safety of pre-operative localization of ground glass nodule (GGN) using embolization microcoils and the locating needles designed for pulmonary nodules.

Methods: From June 2019 to December 2020, 429 patients who received CT-guided localization of single GGN before video-assisted thoracoscopic surgery (VATS) were enrolled. The diameter and depth of GGNs were 0.84 ± 0.39 cm and 1.66 ± 1.37 cm. Among 429 cases, the first 221 GGNs were marked with microcoils (the microcoil group), and the remaining 208 GGNs were marked with the locating needles designed for pulmonary nodules (the locating needle group). SPSS 17.0 statistical software was used to compare the marking success rate, marking time, marking-related complications between two groups. values < 0.05 were considered statistically significant.

Results: The marking time in the microcoil group was longer than that in the locating needle group (11.1 ± 3.9 vs 8.2 ± 2.0 min, = -7.87, = 0.000). The marking success rate in the microcoil group was lower than that in the locating needle group (91.4% 98.6%, χ = 11.27, = 0.001). In the microcoil group, marking failures included 16 cases of microcoil dislocation and 3 cases of unsatisfactory microcoil position, while all 3 cases of marking failure in the locating needle group were due to unsatisfactory anchor position. No significant differences in the incidence of total complications (23.1% 22.1%), pneumothorax (18.1% 19.2%), hemorrhage (9.5% 9.1%), and hemoptysis (1.8% 1.4%) were observed between the two groups. All the complications were minor and did not need special treatment. Except for one case in the microcoil group, which was converted to thoracotomy, the remaining 428 GGNs were successfully resected by VATS.

Conclusions: It is safe and effective to perform pre-operative localization of GGN using either embolization microcoil or the locating needle designed for pulmonary nodules. The locating needle is superior to microcoil for marking GGN in terms of procedure time and the success rate. The complication rate of both methods is similar.

Advances In Knowledge: The locating needle designed for pulmonary nodules has recently been used to mark pulmonary nodule. Its structure can effectively avoid dislocation after localization, and the marking process is simple and quick. Compared with localization using microcoil, it takes less time and has higher success rate to mark GGNs using the locating needle. The complication rate of both methods is similar.
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http://dx.doi.org/10.1259/bjr.20210193DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8248215PMC
July 2021

A smartphone-based online tool for prehospital self-triage of COVID-19.

Chin J Acad Radiol 2020 Nov 16:1-6. Epub 2020 Nov 16.

Department of Radiology, Health Science Center, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, 3002 SunGangXi Road, Shenzhen, 518035 China.

The COVID-19 epidemic has swept across China and spread to other countries. The rapid spreading of COVID-19 and panic combined with the lack of a hierarchical medical system in China have resulted in a huge number of hospital visiting which are overwhelming local medical system and increasing the incidence of cross infection. To meliorate this situation, we adopted the management concept of the system of Tiered Diagnosis and Treatment and developed an online tool for self-triage based on the mostly used multi-purpose smartphone app Wechat in China. This online tool helps people perform self-triage so that they can decide whether to quarantine at home or visit hospital. This tool further provides instructions for home quarantine and help patients make an appointment online if hospital visiting suggested. This smartphone application can reduce the burden on hospitals without losing the truly COVID-19 patients and protect people from the danger of cross infection.
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http://dx.doi.org/10.1007/s42058-020-00051-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7667281PMC
November 2020

Analysis of 4 imaging features in patients with COVID-19.

BMC Med Imaging 2020 07 23;20(1):84. Epub 2020 Jul 23.

Department of Imaging, Shenzhen Second People's Hospital / the First Affiliated Hospital of Shenzhen University, Shenzhen, 518035, Guangdong Province, China.

Background: The aim of this was to analyze 4 chest CT imaging features of patients with coronavirus disease 2019 (COVID-19) in Shenzhen, China so as to improve the diagnosis of COVID-19.

Methods: Chest CT of 34 patients with COVID-19 confirmed by the nucleic acid test (NAT) were retrospectively analyzed. Analyses were performed to investigate the pathological basis of four imaging features("feather sign","dandelion sign","pomegranate sign", and "rime sign") and to summarize the follow-up results.

Results: There were 22 patients (65.2%) with typical "feather sign"and 18 (52.9%) with "dandelion sign", while few patients had "pomegranate sign" and "rime sign". The "feather sign" and "dandelion sign" were composed of stripe or round ground-glass opacity (GGO), thickened blood vessels, and small-thickened interlobular septa. The "pomegranate sign" was characterized as follows: the increased range of GGO, the significant thickening of the interlobular septum, complicated with a small amount of punctate alveolar hemorrhage. The "rime sign" was characterized by numerous alveolar edemas. Microscopically, the wall thickening, small vascular proliferation, luminal stenosis, and occlusion, accompanied by interstitial infiltration of inflammatory cells, as well as numerous pulmonary interstitial fibrosis and partial hyaline degeneration were observed. Repeated chest CT revealed the mediastinal lymphadenectasis in one patient. Re-examination of the NAT showed another positive anal swab in two patients.

Conclusion: "Feather sign" and "dandelion sign" were typical chest CT features in patients withCOVID-19; "pomegranate sign" was an atypical feature, and "rime sign" was a severe feature. In clinical work, accurate identification of various chest CT signs can help to improve the diagnostic accuracy of COVID-19 and reduce the misdiagnosis or missed diagnosis rate.
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http://dx.doi.org/10.1186/s12880-020-00484-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7376520PMC
July 2020

Creating Complex Polyacrylamide Hydrogel Structures Using 3D Printing with Applications to Mechanobiology.

Authors:
Yu-Li Wang David Li

Macromol Biosci 2020 07 17;20(7):e2000082. Epub 2020 Jun 17.

Department of Biomedical Engineering, Scott Hall 4N209, Carnegie Mellon University, 5000 Forbes Avenue, Pittsburgh, PA, 15213, USA.

Due to its favorable physical and chemical properties, including chemical inertness, low fouling by biological molecules, high porosity and permeability, optical transparency, and adjustable elasticity, polyacrylamide has found a wide range of biomedical and non-biomedical applications. To further increase its versatility, this communication describes a simple method, using readily available reagents and equipment, for 3D printing polyacrylamide hydrogels at a resolution of 100-150 μm to create complex structures. As a demonstration of the application, the method is used for creating a lab-on-a-chip cell culture surface with micropatterned stiffness, which then leads to the discovery of stiffness-guided collective cell segregation distinct from durotaxis. The present technology is expected to unleash new applications such as the construction of biocompatible elastic medical devices and artificial organs.
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http://dx.doi.org/10.1002/mabi.202000082DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7482135PMC
July 2020

Infection Control against COVID-19 in Departments of Radiology.

Acad Radiol 2020 May 8;27(5):614-617. Epub 2020 Apr 8.

Department of Radiology, The First Affiliated Hospital of Shenzhen University, Health Science Center, Shenzhen Second People's Hospital, 3002 SunGangXi Road, Shenzhen 518035, China.

The COVID-19 epidemic, which is caused by the novel coronavirus SARS-CoV-2, has spread rapidly to become a world-wide pandemic. Chest radiography and chest CT are frequently used to support the diagnosis of COVID-19 infection. However, multiple cases of COVID-19 transmission in radiology department have been reported. Here we summarize the lessons we learned and provide suggestions to improve the infection control and prevention practices of healthcare workers in departments of radiology.
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http://dx.doi.org/10.1016/j.acra.2020.03.025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7141462PMC
May 2020

Prediction of intravenous immunoglobulin resistance in Kawasaki disease in children.

World J Pediatr 2020 Dec 30;16(6):607-613. Epub 2020 Mar 30.

Department of Pediatrics, Peking University First Hospital, No. 1 Xi'an Men Street, Xicheng District, Beijing, China.

Background: We aimed to explore predictive measures for intravenous immunoglobulin (IVIG) resistance in children with Kawasaki disease (KD).

Methods: Patients diagnosed with KD were enrolled in this study. Univariate analysis and multiple logistic regression were utilized to analyze the clinical features and laboratory results prior to IVIG-treatment of the two groups. Independent predictors of IVIG resistance were analyzed, and a predictive model for KD children with IVIG resistance was constructed.

Results: A total of 277 children with KD, 180 boys and 97 girls, aged 2-128 (median 23) months, were enrolled in the study. Compared with the IVIG-responsive group, the IVIG-resistant group had higher levels of the peripheral neutrophil count, mean platelet volume, mean platelet volume-to-lymphocyte ratio and C-reactive protein, and total serum bilirubin, but lower levels of peripheral lymphocyte count, serum albumin and serum prealbumin. Age (in months), peripheral neutrophil count, lymphocyte count and mean platelet volume and serum albumin were independent indicators for IVIG resistance by multivariate logistic regression analysis. A logistic regression model and a scoring system were set up, where cut-off values of - 0.46 and 6.5 points yielded sensitivities of 83.9% and 77.4%, and specificities of 74.8% and 61.0%, respectively. The areas under the curve (AUC) were 0.808 in the logistic regression model, and 0.750 in the scoring system.

Conclusion: Our model for predicting IVIG-resistant children with KD, involving age (months), peripheral neutrophil count, lymphocyte count and mean platelet volume and serum albumin prior to IVIG-treatment, is helpful for clinical prediction of children with IVIG-resistant KD.
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http://dx.doi.org/10.1007/s12519-020-00348-2DOI Listing
December 2020

Corona Virus International Public Health Emergencies: Implications for Radiology Management.

Acad Radiol 2020 04 26;27(4):463-467. Epub 2020 Feb 26.

Department of Radiology, The First Affiliated Hospital of Shenzhen University, Health Science Center, Shenzhen Second People's Hospital, 3002 SunGangXi Road, Shenzhen, 518035, China.

The outbreak of 2019 novel coronavirus (2019-nCoV) pneumonia was reported in Wuhan, Hubei Province, China in December 2019 and has spread internationally. This article discusses how radiology departments can most effectively respond to this public health emergency.
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http://dx.doi.org/10.1016/j.acra.2020.02.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7102529PMC
April 2020

MicroRNA-147b promotes lung adenocarcinoma cell aggressiveness through negatively regulating microfibril-associated glycoprotein 4 (MFAP4) and affects prognosis of lung adenocarcinoma patients.

Gene 2020 Mar 26;730:144316. Epub 2019 Dec 26.

Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, National Clinical Research Center for Cancer, Tianjin 300000, PR China; Cancer Center, Tianjin Nankai Hospital, Tianjin 300000, PR China. Electronic address:

Background: Lung adenocarcinoma (LUAD) is widely known as the leading cause of death in patients with lung cancer. Extensive evidence has determined that microRNAs (miRNAs) exert critical effects on various biological processes in tumorigenesis. microRNA-147b (miR-147b) has been reported to serve as an oncogenic molecule in colorectal cancer and hepatocellular carcinoma, however, its prognostic value and biological effect in LUAD remain rare.

Materials And Methods: miR-147b and microfibril-associated glycoprotein 4 (MFAP4) data were collected from The Cancer Genome Atlas (TCGA) database to determine their expression levels in LUAD tissues. Kaplan-Meier method was used to plot the overall survival curves for the prognostic power of miR-147b and MFAP4 identification. Chi-square test was utilized to demonstrate the association between clinical characteristics and miR-147b or MFAP4 in LUAD. Luciferse reporter assay was implemented to identify the correlation between miR-147b and MFAP4. The mRNA and protein levels were detected by qRT-PCR and western blotting, respectively. To explore the effects of miR-147b and its potential mechanism in LUAD, cell counting kit 8 (CCK-8), colony formation and transwell assays were performed in LUAD cells with abnormal expression of miR-147b or/and MFAP4.

Results: Our results showed that miR-147b was up-regulated in LUAD tissues and cell lines, which induced poor outcome. Conversely, MFAP4, the putative target gene of miR-147b, was down-regulated in LUAD. The expression of MFAP4 in LUAD cells was negatively regulated by miR-147b. Results of experiments in vitro revealed that miR-147b could promote cell proliferation, colony formation, invasion and migration, while up-regulation of MFAP4 suppressed the impacts of miR-147b on cell malignant aggressiveness in A549 and Calu-3 cells.

Conclusion: In conclusion, these findings determined that miR-147b contributed to the progression of LUAD via targeting MFAP4. Thus, understanding the potential mechanism of miR-147b/MFAP4 may improve the treatment of cancers, especially LUAD.
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http://dx.doi.org/10.1016/j.gene.2019.144316DOI Listing
March 2020

Migration regulates cellular mechanical states.

Mol Biol Cell 2019 12 6;30(26):3104-3111. Epub 2019 Nov 6.

Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, PA 15213.

Recent studies indicate that adherent cells are keenly sensitive to external physical environment, such as substrate rigidity and topography, and internal physical states, such as cell shape and spreading area. Many of these responses are believed to involve coupled output and input of mechanical forces, which may constitute the key sensing mechanism to generate downstream regulatory signals for cell growth and differentiation. Here, we show that the state of cell migration also plays a regulatory role. Compared with migrating cells, stationary cells generate stronger, less dynamic, and more peripherally localized traction forces. These changes are coupled to reduced focal adhesion turnover and enhanced paxillin phosphorylation. Further, using cells migrating along checkerboard micropatterns, we show that the appearance of new focal adhesions directly in front of existing focal adhesions is associated with the down-regulation of existing focal adhesions and associated traction forces. Together, our results imply a mechanism where cell migration regulates traction forces by promoting dynamic turnover of focal adhesions, which may then regulate processes such as wound healing and embryogenesis where cell differentiation must coordinate with migration state and proper localization.
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http://dx.doi.org/10.1091/mbc.E19-02-0099DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6938245PMC
December 2019

Genetic Variants in EGFR/PLCE1 Pathway Are Associated with Prognosis of Esophageal Squamous Cell Carcinoma after Radical Resection.

Curr Med Sci 2019 Jun 17;39(3):385-390. Epub 2019 Jun 17.

Department of Oncology, the First Affiliated Hospital of the Medical College, Shihezi University, Shihezi, 832008, China.

Esophageal cancer (EC) is one of the most deadly malignant diseases. Several studies revealed that variations of the phospholipase C epsilon 1 (PLCE1) gene were associated with EC susceptibility. PLCE1 is located downstream of the epidermal growth factor receptor (EGFR) pathway. Presently, the single nucleotide polymorphisms (SNPs) of EGFR/PLCE1 genes and their associations with EC survival remain unclear. In this study, the associations between genetic variants in the EGFR/PLCE1 pathway and prognosis in 124 esophageal squamous cell carcinoma (ESCC) patients with radical resection were explored. The results showed that CC genotype of both PLCE1 rs17109671 and EGFR rs2072454 was associated with ESCC prognosis. Multivariate analysis revealed that patients with the two unfavorable genotypes had the worst overall survival (OS) or disease-free survival (DFS) (HR=6.099, 95%CI=1.903-19.552; HR=3.994, 95%CI=1.49-10.702, respectively). Additionally, combination of SNPs and tumor stage could better predict OS (for AUC, 0.774 vs. 0.709) and PFS (for AUC, 0.773 vs. 0.704) than tumor stage alone. In conclusion, genetic variants of the EGFR/PLCE1 may be predictors of the prognosis of ESCC after surgery. The individuals with the CC genotype of PLCE1 rs17109671 and EGFR rs2072454 should receive more aggressive treatments.
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http://dx.doi.org/10.1007/s11596-019-2047-xDOI Listing
June 2019

Redundant and Nonredundant Information for Model Calibration or Hydraulic Tomography.

Ground Water 2020 01 1;58(1):79-92. Epub 2019 Apr 1.

Safety, Health, and Environmental Center, Group Administration, Formosa Plastics Group, 201, Tunghwa North Road, Taipei, 10508, Taiwan.

Drawdown data from independent pumping tests have widely been used to validate the estimated hydraulic parameters from inverse modeling or hydraulic tomography (HT). Yet, the independent pumping test has not been clearly defined. Therefore, the goal of this paper is to define this independent pumping test concept, based on the redundant or nonredundant information about aquifer heterogeneity embedded in the observed heads during cross-hole pumping tests. The definition of complete, moderate redundancy and high nonredundancy of information are stipulated using cross-correlation analysis of the relationship between the head and heterogeneity. Afterward, data from numerical experiments and field sequential pumping test campaigns reinforce the concept and the definition.
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http://dx.doi.org/10.1111/gwat.12879DOI Listing
January 2020

Improving antitumor outcomes for palliative intratumoral injection therapy through lecithin- chitosan nanoparticles loading paclitaxel- cholesterol complex.

Int J Nanomedicine 2019 23;14:689-705. Epub 2019 Jan 23.

State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, P.R. China,

Background: Intratumoral injection is a palliative treatment that aims at further improvement in the survival and quality of life of patients with advanced or recurrent carcinomas, or cancer patients with severe comorbidities or those with a poor performance status.

Methods: In this study, a solvent-injection method was used to prepare paclitaxel-cholesterol complex-loaded lecithin-chitosan nanoparticles (PTX-CH-loaded LCS_NPs) for intratumoral injection therapy, and the physicochemical properties of NPs were well characterized.

Results: The particle size and zeta potential of PTX-CH-loaded LCS_NPs were 142.83±0.25 nm and 13.50±0.20 mV, respectively. Release behavior of PTX from PTX-CH-loaded LCS_NPs showed a pH-sensitive pattern. The result of cell uptake assay showed that PTX-CH-loaded LCS_NPs could effectively enter cells via the energy-dependent caveolae-mediated endocytosis and macropinocytosis in company with the Golgi apparatus. Meanwhile, PTX-CH-loaded LCS_NPs had a better ability to induce cell apoptosis than PTX solution. The in vivo antitumor results suggested that PTX-CH-loaded LCS_NPs effectively inhibited mouse mammary cancer growth and metastasis to distant organs and significantly improved the survival rate of tumor-bearing mice by intratumoral administration.

Conclusion: In general, our study demonstrated that PTX-CH-loaded LCS_NPs used for palliative treatment by intratumoral injection showed improved safety and antitumor efficacy, which provided an alternative approach in the field of palliative chemotherapy.
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http://dx.doi.org/10.2147/IJN.S188667DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6361321PMC
March 2019

Sirtuin 4 Depletion Promotes Hepatocellular Carcinoma Tumorigenesis Through Regulating Adenosine-Monophosphate-Activated Protein Kinase Alpha/Mammalian Target of Rapamycin Axis in Mice.

Hepatology 2019 04 12;69(4):1614-1631. Epub 2019 Mar 12.

Berkeley Biomedical Data Science Center, Lawrence Berkeley National Laboratory, Berkeley, CA.

Sirtuin 4 (SIRT4) has been reported to play a vital role in the maintenance of glutamine catabolism and adenosine triphosphate (ATP) homeostasis, but its character in hepatocellular carcinomas (HCCs) remains obscure. In this study, we observed low expression of SIRT4 in both HCC cell lines and HCCs from patients. Decreased disease-free survival time is associated with low tumor levels of SIRT4 in patients. Deficiency of SIRT4 facilitated liver tumor development and lung metastasis in xenografts and knockout (KO) mice by promoting colony formation and migration of hepatoma cells and enhancing sphere formation of HCCs. Mechanistically, SIRT4 deletion augmented mammalian target of rapamycin (mTOR) signaling by inactivating adenosine-monophosphate (AMP)-activated protein kinase alpha (AMPKα) through regulation of glutamine catabolism and subsequent AM)/liver kinase B1 (LKB1) axis. Blockage of mTOR by rapamycin or inhibition of glutaminolysis abolished the discrepancy in tumorigenic capacity between SIRT4-depleted hepatoma cells and control cells. Suppression of LKB1 or promotion of AMP by metformin also abrogated the hyperproliferative phenotype caused by SIRT4 loss, which further confirmed that the LKB1/AMPKα/mTOR axis is required in SIRT4-deficiency-promoted HCC tumorigenesis. Conclusion: SIRT4 could exert its tumor suppressive function in HCC by inhibiting glutamine metabolism and thereby increasing the adenosine diphosphate (ADP)/AMP levels to phosphorylate AMPKα by LKB1, which blocks the mTOR signaling pathway.
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http://dx.doi.org/10.1002/hep.30421DOI Listing
April 2019

Coordination of cell migration mediated by site-dependent cell-cell contact.

Authors:
David Li Yu-Li Wang

Proc Natl Acad Sci U S A 2018 10 1;115(42):10678-10683. Epub 2018 Oct 1.

Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, PA 15213

Contact inhibition of locomotion (CIL), the repulsive response of cells upon cell-cell contact, has been the predominant paradigm for contact-mediated responses. However, it is difficult for CIL alone to account for the complex behavior of cells within a multicellular environment, where cells often migrate in cohorts such as sheets, clusters, and streams. Although cell-cell adhesion and mechanical interactions play a role, how individual cells coordinate their migration within a multicellular environment remains unclear. Using micropatterned substrates to guide cell migration and manipulate cell-cell contact, we show that contacts between different regions of cells elicit different responses. Repulsive responses were limited to interaction with the head of a migrating cell, while contact with the tail of a neighboring cell promoted migration toward the tail. The latter behavior, termed contact following of locomotion (CFL), required the Wnt signaling pathway. Inhibition of the Wnt pathway disrupted not only CFL but also collective migration of epithelial cells, without affecting the migration of individual cells. In contrast, inhibition of myosin II with blebbistatin disrupted the migration of both individual epithelial cells and collectives. We propose that CFL, in conjunction with CIL, plays a major role in guiding and coordinating cell migration within a multicellular environment.
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http://dx.doi.org/10.1073/pnas.1807543115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6196508PMC
October 2018

miR-34a Regulates Multidrug Resistance via Positively Modulating OAZ2 Signaling in Colon Cancer Cells.

J Immunol Res 2018 2;2018:7498514. Epub 2018 Aug 2.

Department of Medical Oncology, First Affiliated Hospital of Medical College of Shihezi University, Shihezi, Xinjiang Uygur Autonomous Region 832000, China.

Although aberrant expression of miR-34a, an essential tumor suppressor miRNA, has been frequently observed in colon cancer (CCa), whether miR-34a can regulate CCa progression by modulating other facets of this malignancy (such as multidrug resistance, MDR) remains unknown. Here, we report for the first time that miR-34a expression was significantly downregulated in clinical CCa samples from oxaliplatin-resistant patients and in experimentally established multidrug-resistant CCa cells. By using histoculture drug response assay, we further confirmed that clinical CCa samples with lower miR-34a expression appeared to be more resistant to chemotherapy. Functionally, ectopic expression of exogenous miR-34a resensitized multidrug-resistant HCT-8/OR cells to oxaliplatin treatment, whereas miR-34a inhibition augmented the oxaliplatin resistance in chemosensitive HCT-8 cells. Mechanistically, miR-34a positively regulated the mRNA stability of the ornithine decarboxylase antizyme 2 (OAZ2) by directly targeting its three prime untranslated region (3'UTR). Consequently, suppression of the expression of miR-34a/OAZ2 signaling by chemotherapeutic agents significantly enhanced the activation of MDR-associated ATP-binding cassette (ABC) transporters and antiapoptosis pathways, thus leading to MDR development in CCa cells. Collectively, our combined analysis reveals a critical role of miR-34a/OAZ2 cascade in conferring a proper cellular response to CCa chemotherapy.
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http://dx.doi.org/10.1155/2018/7498514DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6098920PMC
November 2018

[Simulating the effects of climate change and fire disturbance on aboveground biomass of boreal forests in the Great Xing'an Mountains, Northeast China].

Ying Yong Sheng Tai Xue Bao 2018 Mar;29(3):713-724

Faculty of Architectural, Civil Engineering and Environment, Ningbo University, Ningbo 315211, Zhejiang, China.

Predicting the effects of climate warming and fire disturbance on forest aboveground biomass is a central task of studies in terrestrial ecosystem carbon cycle. The alteration of temperature, precipitation, and disturbance regimes induced by climate warming will affect the carbon dynamics of forest ecosystem. Boreal forest is an important forest type in China, the responses of which to climate warming and fire disturbance are increasingly obvious. In this study, we used a forest landscape model LANDIS PRO to simulate the effects of climate change on aboveground biomass of boreal forests in the Great Xing'an Mountains, and compared direct effects of climate warming and the effects of climate warming-induced fires on forest aboveground biomass. The results showed that the aboveground biomass in this area increased under climate warming scenarios and fire disturbance scenarios with increased intensity. Under the current climate and fire regime scenario, the aboveground biomass in this area was (97.14±5.78) t·hm, and the value would increase up to (97.93±5.83) t·hm under the B1F2 scenario. Under the A2F3 scenario, aboveground biomass at landscape scale was relatively higher at the simulated periods of year 100-150 and year 150-200, and the value were (100.02±3.76) t·hm and (110.56±4.08) t·hm, respectively. Compared to the current fire regime scenario, the predicted biomass at landscape scale was increased by (0.56±1.45) t·hm under the CF2 scenario (fire intensity increased by 30%) at some simulated periods, and the aboveground biomass was reduced by (7.39±1.79) t·hm in CF3 scenario (fire intensity increased by 230%) at the entire simulation period. There were significantly different responses between coniferous and broadleaved species under future climate warming scenarios, in that the simulated biomass for both Larix gmelinii and Betula platyphylla showed decreasing trend with climate change, whereas the simulated biomass for Pinus sylvestris var. mongolica, Picea koraiensis and Populus davidiana showed increasing trend at different degrees during the entire simulation period. There was a time lag for the direct effect of climate warming on biomass for coniferous and broadleaved species. The response time of coniferous species to climate warming was 25-30 years, which was longer than that for broadleaf species. The forest landscape in the Great Xing'an Mountains was sensitive to the interactive effect of climate warming (high CO emissions) and high intensity fire disturbance. Future climate warming and high intensity forest fire disturbance would significantly change the composition and structure of forest ecosystem.
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http://dx.doi.org/10.13287/j.1001-9332.201803.011DOI Listing
March 2018

Finite analytic method for modeling variably saturated flows.

Sci Total Environ 2018 Apr 13;621:1151-1162. Epub 2017 Nov 13.

Key Laboratory of Subsurface Hydrology and Ecological Effects in Arid Region, Chang'an University, Ministry of Education, PR China; School of Environmental Science and Engineering, Chang'an University, PR China.

This paper develops a finite analytic method (FAM) for solving the two-dimensional Richards' equation. The FAM incorporates the analytic solution in local elements to formulate the algebraic representation of the partial differential equation of unsaturated flow so as to effectively control both numerical oscillation and dispersion. The FAM model is then verified using four examples, in which the numerical solutions are compared with analytical solutions, solutions from VSAFT2, and observational data from a field experiment. These numerical experiments show that the method is not only accurate but also efficient, when compared with other numerical methods.
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http://dx.doi.org/10.1016/j.scitotenv.2017.10.112DOI Listing
April 2018

Centrosome defines the rear of cells during mesenchymal migration.

Mol Biol Cell 2017 Nov 30;28(23):3240-3251. Epub 2017 Aug 30.

Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, PA 15213

The importance of centrosome in directional cell migration has long been recognized. However, the conventional view that centrosome determines cell's front, based on its often-observed position in front of the nucleus, has been challenged by contradictory observations. Here we show that centrosome defines the rear instead of the front, using cells plated on micropatterned adhesive strips to facilitate directional migration. We found that centrosome is always located proximal to the future rear before polarity is established through symmetry breaking or reversed as the cell reaches a dead end. In addition, using microsurgery to alter the distance of centrosomes from cells' ends, we show that centrosomal proximity is predictive of the placement of the rear. Removal of centrosome impairs directional cell migration, whereas the removal of nucleus alone makes no difference in most cells. Computer modeling under the framework of a local-enhancement/global-inhibition mechanism further demonstrates that positioning of rear retraction, mediated by signals concentrated near the centrosome, recapitulates all the experimental observations. Our results resolve a long-standing controversy and explain how cells use centrosome and microtubules to maintain directional migration.
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http://dx.doi.org/10.1091/mbc.E17-06-0366DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5687026PMC
November 2017

Clinical significance of circulating tumor cells in patients with small-cell lung cancer.

Tumori 2017 May 15;103(3):242-248. Epub 2017 Feb 15.

Department of Oncology, Shihezi University School of Medicine, The First Affiliated Hospital, Shihezi - China.

Background: This study investigated the correlation of the presence of circulating tumor cells (CTCs) with clinical characteristics, and the predictive value of CTCs for progression-free survival (PFS) in patients with small-cell lung cancer (SCLC).

Methods: Samples were obtained from 42 patients with SCLC before and after the first cycle of chemotherapy. CTCs were quantitated by negative immunomagnetic enrichment and immunocytochemistry using anti-CD45 and anti-pancytokeratin antibodies.

Results: CTCs were positive (≥2) in 76.19% of patients with SCLC and negative in the control group. The presence of CTCs was positively correlated with 6 clinical characteristics. PFS was 6.055 and 10.670 months for patients with ≥2 and <2 CTCs/7.5 mL of blood before chemotherapy; after chemotherapy PFS was 4.862 and 10.535 months, respectively.

Conclusions: This study showed that both baseline CTC numbers and the change in CTC numbers after 1 cycle of chemotherapy are significant prognostic factors of PFS for SCLC.
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http://dx.doi.org/10.5301/tj.5000601DOI Listing
May 2017

Auto-Induction Effect of Chloroxoquinoline on the Cytochrome P450 Enzymes of Rats Associated with CYP 3A and 1A.

PLoS One 2015 23;10(9):e0138875. Epub 2015 Sep 23.

Beijing Institute of Pharmacology and Toxicology, Beijing, China.

To investigate the auto-induction of cytochrome P450 (CYP450) by Chloroxoquinoline (CXL), a novel anticancer drug. Three experiments related to the induction of CYP450 were performed: a) In vitro use of the rat fresh hepatocytes model; b) In vivo 'cocktail' of CYP450 probe model; c) Pharmacokinetic (PK) study of the single and multiple doses. Some typical CYP enzyme probes and inducers were used in these experiments and were all determined by HPLC-MS/MS. The expression levels of CYP3A and CYP1A mRNA were analyzed by the real time polymerase chain reaction (RT-PCR) technique. The PK studies showed that the area under the curve (AUC0-t) and the peak concentration (Cmax) of the multiple doses were approximately 2.4-fold and 1.9-fold lower than those of the single dose, respectively (p < 0.05). Subsequent studies were conducted to study the possible induction of CXL on CYP 450. The in vivo 'cocktail' administration of CYP450 probe model indicated that 5 d pretreatment with CXL resulted in a mean 4.6 times increase in the metabolites/probe plasma ratios for CYP 3A and a 336% increase for CYP 1A than those of the negative control (p < 0.05). The induction effect of CXL on CYP450 was further evaluated on rat hepatocytes with four concentrations (1, 10, 50 and 100 μmol/L). Compared with the negative control, the mRNA levels of CYP 1A2 increased significantly in rat hepatocytes after treatment with 10, 50 and 100 μmol/L CXL (p < 0.05). While significant inductions of CYP 3A1 were observed in the entire treated groups. The results of the present study demonstrate enhanced and induced expression of CYP 3A and CYP 1A in response to CXL exposure in rats, suggesting that CXL is an auto-inducer of CYP 3A and CYP 1A.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0138875PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4580629PMC
May 2016

Non-muscle myosin IIB is critical for nuclear translocation during 3D invasion.

J Cell Biol 2015 Aug 10;210(4):583-94. Epub 2015 Aug 10.

Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 441195 Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH 44195

Non-muscle myosin II (NMII) is reported to play multiple roles during cell migration and invasion. However, the exact biophysical roles of different NMII isoforms during these processes remain poorly understood. We analyzed the contributions of NMIIA and NMIIB in three-dimensional (3D) migration and in generating the forces required for efficient invasion by mammary gland carcinoma cells. Using traction force microscopy and microfluidic invasion devices, we demonstrated that NMIIA is critical for generating force during active protrusion, and NMIIB plays a major role in applying force on the nucleus to facilitate nuclear translocation through tight spaces. We further demonstrate that the nuclear membrane protein nesprin-2 is a possible linker coupling NMIIB-based force generation to nuclear translocation. Together, these data reveal a central biophysical role for NMIIB in nuclear translocation during 3D invasive migration, a result with relevance not only to cancer metastasis but for 3D migration in other settings such as embryonic cell migration and wound healing.
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http://dx.doi.org/10.1083/jcb.201502039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4539979PMC
August 2015

Functional maturation of human pluripotent stem cell derived cardiomyocytes in vitro--correlation between contraction force and electrophysiology.

Biomaterials 2015 May 18;51:138-150. Epub 2015 Feb 18.

Department of Anatomy & Embryology, Leiden University Medical Center, Leiden, The Netherlands. Electronic address:

Cardiomyocytes from human pluripotent stem cells (hPSC-CM) have many potential applications in disease modelling and drug target discovery but their phenotypic similarity to early fetal stages of cardiac development limits their applicability. In this study we compared contraction stresses of hPSC-CM to 2nd trimester human fetal derived cardiomyocytes (hFetal-CM) by imaging displacement of fluorescent beads by single contracting hPSC-CM, aligned by microcontact-printing on polyacrylamide gels. hPSC-CM showed distinctly lower contraction stress than cardiomyocytes isolated from hFetal-CM. To improve maturation of hPSC-CM in vitro we made use of commercial media optimized for cardiomyocyte maturation, which promoted significantly higher contraction stress in hPSC-compared with hFetal-CM. Accordingly, other features of cardiomyocyte maturation were observed, most strikingly increased upstroke velocities and action potential amplitudes, lower resting membrane potentials, improved sarcomeric organization and alterations in cardiac-specific gene expression. Performing contraction force and electrophysiology measurements on individual cardiomyocytes revealed strong correlations between an increase in contraction force and a rise of the upstroke velocity and action potential amplitude and with a decrease in the resting membrane potential. We showed that under standard differentiation conditions hPSC-CM display lower contractile force than primary hFetal-CM and identified conditions under which a commercially available culture medium could induce molecular, morphological and functional maturation of hPSC-CM in vitro. These results are an important contribution for full implementation of hPSC-CM in cardiac disease modelling and drug discovery.
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http://dx.doi.org/10.1016/j.biomaterials.2015.01.067DOI Listing
May 2015

Fibroblasts probe substrate rigidity with filopodia extensions before occupying an area.

Proc Natl Acad Sci U S A 2014 Dec 17;111(48):17176-81. Epub 2014 Nov 17.

Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, PA 15219

Rigidity sensing and durotaxis are thought to be important elements in wound healing, tissue formation, and cancer treatment. It has been challenging, however, to study the underlying mechanism due to difficulties in capturing cells during the transient response to a rigidity interface. We have addressed this problem by developing a model experimental system that confines cells to a micropatterned area with a rigidity border. The system consists of a rigid domain of one large adhesive island, adjacent to a soft domain of small adhesive islands grafted on a nonadhesive soft gel. This configuration allowed us to test rigidity sensing away from the cell body during probing and spreading. NIH 3T3 cells responded to the micropatterned rigidity border similarly to cells at a conventional rigidity border, by showing a strong preference for staying on the rigid side. Furthermore, cells used filopodia extensions to probe substrate rigidity at a distance in front of the leading edge and regulated their responses based on the strain of the intervening substrate. Soft substrates inhibited focal adhesion maturation and promoted cell retraction, whereas rigid substrates allowed stable adhesions and cell spreading. Myosin II was required for not only the generation of probing forces but also the retraction in response to soft substrates. We suggest that a myosin II-driven, filopodia-based probing mechanism ahead of the leading edge allows cells to migrate efficiently, by sensing physical characteristics before moving over a substrate to avoid backtracking.
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http://dx.doi.org/10.1073/pnas.1412285111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4260597PMC
December 2014

Microtubules stabilize cell polarity by localizing rear signals.

Proc Natl Acad Sci U S A 2014 Nov 3;111(46):16383-8. Epub 2014 Nov 3.

Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, PA 15219

Microtubules are known to play an important role in cell polarity; however, the mechanism remains unclear. Using cells migrating persistently on micropatterned strips, we found that depolymerization of microtubules caused cells to change from persistent to oscillatory migration. Mathematical modeling in the context of a local-excitation-global-inhibition control mechanism indicated that this mechanism can account for microtubule-dependent oscillation, assuming that microtubules remove inhibitory signals from the front after a delayed generation. Experiments further supported model predictions that the period of oscillation positively correlates with cell length and that oscillation may be induced by inhibiting retrograde motors. We suggest that microtubules are required not for the generation but for the maintenance of cell polarity, by mediating the global distribution of inhibitory signals. Disassembly of microtubules induces cell oscillation by allowing inhibitory signals to accumulate at the front, which stops frontal protrusion and allows the polarity to reverse.
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http://dx.doi.org/10.1073/pnas.1410533111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4246331PMC
November 2014
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