Publications by authors named "Guobin Wang"

188 Publications

pH-Triggered nanoreactors as oxidative stress amplifiers for combating multidrug-resistant biofilms.

Chem Commun (Camb) 2021 May;57(38):4662-4665

Department of Clinical Laboratory, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. and Research Center for Tissue Engineering and Regenerative Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.

Developing radical oxygen species (ROS)-generating nanoreactors as new "antibiotics" is a promising strategy for the treatment of multidrug-resistant (MDR) biofilm infections. Herein, we designed and fabricated silver nanoparticle-decorated calcium peroxide (CaO2) nanoreactors (CPA) for combating MDR biofilms. CPA could locally boost ROS production as oxidative stress amplifiers in a pH-triggered and self-catalytic manner in acidic biofilms, where H2O2 was released by the hydrolysis of CaO2 and sequentially catalyzed by Ag NPs in situ to generate O2˙-, thereby efficiently disrupting mature biofilms and killing bacteria.
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http://dx.doi.org/10.1039/d1cc00247cDOI Listing
May 2021

Role of Indole-3-Acetic Acid in NAFLD Amelioration After Sleeve Gastrectomy.

Obes Surg 2021 May 10. Epub 2021 May 10.

Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.

Background: This study aimed to investigate the weight-independent mechanism of sleeve gastrectomy on the relief of nonalcoholic fatty liver disease (NAFLD).

Methods: A total of 58 obese patients who had undergone sleeve gastrostomy (SG) were recruited. Plasma levels of indole-3-acetic acid (I3A), a metabolite from gut microbiota before and after SG were investigated. In addition, we had 78 C57BL/6J mice included in the study. High-fat diet (HFD) was used to induce obesity in mice. Sleeve gastrectomy (SG) was then performed. The liver of the mice was analyzed by HE and oil red staining to study lipid accumulation. Fluorescence-activated cell sorting (FACS) analysis was performed to study the phenotype of macrophages in the liver. The levels of I3A in serum, stool, and liver were tested by ELISA. Macrophages and hepatocytes were cultured in vitro and stimulated with I3A to study the effects on differentiation and proliferation/apoptosis.

Results: In human samples, I3A increased after SG and plasma I3A levels were positively correlated with liver CT values and negatively correlated with liver fat attenuation. In mice models, after surgery, the percentage of M2 macrophages significantly increased in the liver. Both oral gavage and in vitro stimulation of I3A could promote M2 differentiation and did not significantly affect the state of hepatocytes.

Conclusions: This study suggested that increased I3A from the intestine after SG could reduce the M1/M2 ratio in the liver and thus promote relief of NAFLD in obese individuals. Graphical Abstract.
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http://dx.doi.org/10.1007/s11695-021-05321-0DOI Listing
May 2021

Nkx2.5 Functions as a Conditional Tumor Suppressor Gene in Colorectal Cancer Cells Acting as a Transcriptional Coactivator in p53-Mediated p21 Expression.

Front Oncol 2021 1;11:648045. Epub 2021 Apr 1.

Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

NK2 homeobox 5 (Nkx2.5), a homeobox-containing transcription factor, is associated with a spectrum of congenital heart diseases. Recently, Nkx2.5 was also found to be differentially expressed in several kinds of tumors. In colorectal cancer (CRC) tissue and cells, hypermethylation of Nkx2.5 was observed. However, the roles of Nkx2.5 in CRC cells have not been fully elucidated. In the present study, we assessed the relationship between Nkx2.5 and CRC by analyzing the expression pattern of Nkx2.5 in CRC samples and the adjacent normal colonic mucosa (NCM) samples, as well as in CRC cell lines. We found higher expression of Nkx2.5 in CRC compared with NCM samples. CRC cell lines with poorer differentiation also had higher expression of Nkx2.5. Although this expression pattern makes Nkx2.5 seem like an oncogene, and tumor suppressive effects of Nkx2.5 were detected in HCT116 cells by establishing Nkx2.5-overexpressed CRC cells. However, Nkx2.5 overexpression was incapacitated in SW480 cells. To further assess the mechanism, different expression levels and mutational status of p53 were observed in HCT116 and SW480 cells. The expression of p21, a downstream antitumor effector of p53, in CRC cells depends on both expression level and mutational status of p53. Overexpressed Nkx2.5 could elevate the expression of p21 only in CRC cells with wild-type p53 (HCT116), rather than in CRC cells with mutated p53 (SW480). Mechanistically, Nkx2.5 could interact with p53 and increase the transcription of p21 without affecting the expression of p53. In conclusion, our findings demonstrate that Nkx2.5 could act as a conditional tumor suppressor gene in CRC cells with respect to the mutational status of p53. The tumor suppressive effect of Nkx2.5 could be mediated by its role as a transcriptional coactivator in wild-type p53-mediated p21 expression.
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http://dx.doi.org/10.3389/fonc.2021.648045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8047315PMC
April 2021

TRIM39 deficiency inhibits tumor progression and autophagic flux in colorectal cancer via suppressing the activity of Rab7.

Cell Death Dis 2021 Apr 12;12(4):391. Epub 2021 Apr 12.

Research Center for Tissue Engineering and Regenerative Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430022, Wuhan, China.

The biological function of TRIM39, a member of TRIM family, remains largely unexplored in cancer, especially in colorectal cancer (CRC). In this study, we show that TRIM39 is upregulated in tumor tissues compared to adjacent normal tissues and associated with poor prognosis in CRC. Functional studies demonstrate that TRIM39 deficiency restrains CRC progression in vitro and in vivo. Our results further find that TRIM39 is a positive regulator of autophagosome-lysosome fusion. Mechanistically, TRIM39 interacts with Rab7 and promotes its activity via inhibiting its ubiquitination at lysine 191 residue. Depletion of TRIM39 inhibits CRC progression and autophagic flux in a Rab7 activity-dependent manner. Moreover, TRIM39 deficiency suppresses CRC progression through inhibiting autophagic degradation of p53. Thus, our findings uncover the roles as well as the relevant mechanisms of TRIM39 in CRC and establish a functional relationship between autophagy and CRC progression, which may provide promising approaches for the treatment of CRC.
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http://dx.doi.org/10.1038/s41419-021-03670-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8041807PMC
April 2021

Transcription factor SP1-induced microRNA-146b-3p facilitates the progression and metastasis of colorectal cancer via regulating FAM107A.

Life Sci 2021 Apr 5;277:119398. Epub 2021 Apr 5.

Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address:

Background: Recent studies have provided compelling evidence regarding the association of microRNAs (miRNAs) with the progression and development of tumors. Among the miRNAs, the dysregulation of miR-146b-3p expression has been reported in several cancers, however, its effect on colorectal cancer (CRC) remains unexplored. Many studies have suggested a close correlation between the transcription factor (TF)-miRNA signal and cancer. The present study explored the effects of TF-miR-146b-3p axis on CRC and elucidated its downstream regulatory molecule.

Materials And Methods: The expression levels of miR-146b-3p in CRC tissues and cell lines were assessed via quantitative real-time polymerase chain reaction (qRT-PCR). The impact of miR-146b-3p on CRC cell proliferation, migration, and invasion were analyzed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) cell proliferation assay and transwell migration and invasion assay. Additionally, the impact of miR-146b-3p on CRC cell cycle and apoptosis was investigated using flow cytometry. The targets of miR-146b-3p, predicted by miRWalk database, were verified using a dual-luciferase reporter system. The expression levels of TFs were detected using qRT-PCR. The effects of miR-146b-3p and SP1 on FAM107A expression were assessed by performing qRT-PCR and western blotting. Chromatin Immunoprecipitation (ChIP) Assay was performed and JASPAR database was utilized to explore the regulatory relationship between the SP1 and miR-146b-3p.

Results: Increased expression of miR-146b-3p in CRC tissues and cell lines correlated with poor overall survival (OS). Upregulation of miR-146b-3p expression remarkably promoted the proliferation, migration, and invasion of CRC cells and suppressed their apoptosis. Furthermore, SP1 overexpression significantly elevated the miR-146b-3p expression, decreased the FAM107A expression, and promoted the G1/S transition. The miR-146b-3p overexpression also enhanced the effects of SP1 overexpression on CRC cell proliferation, migration, and invasion, whereas miR-146b-3p knockdown led to the opposite results.

Conclusion: Mechanistically, miR-146b-3p functions as an oncogene by directly targeting FAM107A. Our results highlight the critical regulatory role played by SP1-induced miR-146b-3p expression in CRC development. Our results suggest that SP1/miR-146b-3p/FAM107A axis may be a potential therapeutic target for CRC.
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http://dx.doi.org/10.1016/j.lfs.2021.119398DOI Listing
April 2021

Biological control technology and application based on agricultural unmanned aerial vehicle (UAV) intelligent delivery of insect natural enemies (Trichogramma) carrier.

Pest Manag Sci 2021 Mar 24. Epub 2021 Mar 24.

National Center for International Collaboration Research on Precision Agricultural Aviation Pesticides Spraying Technology (NPAAC), South China Agricultural University, Guangzhou, China.

Background: Agricultural pests and diseases affect grain yield and quality. In addition to the use of chemical agents, the biological control of diseases and insect pests has attracted more and more attention due to an urgent need for environmental protection. However, traditional operational methods do not integrate well with biological control technology. With the advantages of simple operation, low operating cost, high operating efficiency and wide application range, use of multirotor unmanned aerial vehicles (UAVs) in biological control is of great significance.

Results: An intelligent delivery system comprising an insect natural enemy (Trichogramma) capsule based on an M45 electric multirotor UAV was built to release Trichogramma ostriniae in corn fields under full autonomous mode. During operation, the M45 UAV can fly accurately in accordance with operational requirements; average deviation between the actual and planned routes was 0.24 m, the average flight speed was 9.18 m s and the average altitude was 5.08 m. The effective coverage rate of natural enemies was 99.33% and the coverage redundancy was 36.75%. After delivery, an investigation into the field control effect showed an average control effect of 83.70%, which can result in effective pest control.

Conclusion: A natural enemy carrier intelligent delivery system based on an M45 electric multirotor UAV was found to have good flight performance. In addition, natural enemies were evenly distributed, giving even coverage of the target fields. The system had a good control effect.
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http://dx.doi.org/10.1002/ps.6371DOI Listing
March 2021

Injectable silk sericin scaffolds with programmable shape-memory property and neuro-differentiation-promoting activity for individualized brain repair of severe ischemic stroke.

Bioact Mater 2021 Jul 29;6(7):1988-1999. Epub 2020 Dec 29.

Department of Clinical Laboratory, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.

Severe ischemic stroke damages neuronal tissue, forming irregular-shaped stroke cavities devoid of supporting structure. Implanting biomaterials to provide structural and functional support is thought to favor ingrowth of regenerated neuronal networks. Injectable hydrogels capable of gelation are often utilized for stroke repair, but challenged by incomplete gelation and imprecise control over end-macrostructure. Injectable shape-memory scaffolds might overcome these limitations, but are not explored for stroke repair. Here, we report an injectable, photoluminescent, carbon-nanotubes-doped sericin scaffold (CNTs-SS) with programmable shape-memory property. By adjusting CNTs' concentrations, CNTs-SS' recovery dynamics can be mathematically calculated at the scale of seconds, and its shapes can be pre-designed to precisely match any irregular-shaped cavities. Using a preclinical stroke model, we show that CNTs-SS with the customized shape is successfully injected into the cavity and recovers its pre-designed shape to well fit the cavity. Notably, CNTs-SS' near-infrared photoluminescence enables non-invasive, real-time tracking after implantation. Moreover, as a cell carrier, CNTs-SS not only deliver bone marrow mesenchymal stem cells (BMSCs) into brain tissues, but also functionally promote their neuronal differentiation. Together, we for the first time demonstrate the feasibility of applying injectable shape-memory scaffolds for stroke repair, paving the way for personalized stroke repair.
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http://dx.doi.org/10.1016/j.bioactmat.2020.12.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7786039PMC
July 2021

Kupffer Cell-targeting strategy for the protection of Hepatic Ischemia/Reperfusion Injury.

Nanotechnology 2021 Jan 20. Epub 2021 Jan 20.

First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, CHINA.

Hepatic ischemia/reperfusion injury (IRI) seriously affects the prognosis of patients undergoing liver surgery. Liver-resident Kupffer cells have been reported to promote IRI. Nanomedicines are known to be effective in the treatment of liver diseases, however, Kupffer cell-targeting nanomedicines for the treatment of IRI are yet to be developed. As potential bioimaging nanomaterials, rare earth upconversion nanoparticles (UCNs) have been found to specifically deplete Kupffer cells, but the underlying mechanism is unknown. In this study, we found that UCNs specifically depleted Kupffer cells by pyroptosis, while the co-administration of the caspase-1 inhibitor VX-765 rescued the UCN-induced Kupffer cell pyroptosis in mice. Furthermore, the pre-depletion of Kupffer cells by the UCNs significantly suppressed the release of inflammatory cytokines and effectively improved hepatic IRI. The rescue of the pyroptosis of the Kupffer cells by VX-765 abrogated the protective effect of UCNs on the liver. These results suggest that UCNs are highly promising for the development of Kupffer cell-targeting nanomedicines for intraoperative liver protection.
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http://dx.doi.org/10.1088/1361-6528/abde02DOI Listing
January 2021

[Master genes and co-expression network analysis in peripheral blood mononuclear cells of patients with gram-positive and gram-negative sepsis].

Zhejiang Da Xue Xue Bao Yi Xue Ban 2020 Dec;49(6):732-742

Surgical Intensive Care Unit, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.

Objective: To investigate the functional pathways enriched and differentially expressed genes (DEGs) in peripheral blood mononuclear cells (PBMCs) of patients with gram-positive and gram-negative sepsis.

Methods: Dataset GSE9960 obtained from NCBI GEO database containing PBMC samples from 16 non-infectious systematic inflammatory response syndrome (SIRS) patients, 17 gram-positive septic patients and 18 gram-negative septic patients were included in the study. Functional pathway annotations were conducted by gene set enrichment analysis and weighted gene co-expression network analysis. DEGs were filtered and master DEGs were then validated in PBMCs of gram-positive septic, gram-negative septic and non-infectious SIRS patients.

Results: The enriched gene sets in gram-positive sepsis and gram-negative sepsis were significantly different. The results indicated the opposite co-expression networks in SIRS and gram-negative sepsis, and the entirely different co-expression networks in gram-positive and gram-negative sepsis. Furthermore, we validated that was up-regulated in gram-positive sepsis (<0.05), was down-regulated in gram-negative sepsis (<0.01), while was up-regulated in gram-negative sepsis (<0.05).

Conclusions: The results indicate that there are differences in the mechanism and pathogenesis of gram-positive and gram-negative sepsis, which may provide potential markers for sepsis diagnosis and empirical antimicrobial therapy.
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http://dx.doi.org/10.3785/j.issn.1008-9292.2020.12.08DOI Listing
December 2020

Comparative efficacy and tolerability of adjuvant systemic treatments against resectable colon cancer: a network meta-analysis.

Ther Adv Med Oncol 2020 14;12:1758835920974195. Epub 2020 Dec 14.

Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jiefang Avenue, Wuhan 430022, China.

Background: Currently, 6-month oxaliplatin-based chemotherapy has been recommended as the preferred adjuvant treatment against high-risk stage 2 and stage 3 colon cancer patients.

Methods: Record retrieval was conducted in PubMed, Web of Science, Cochrane Central Register of Controlled Trials, American Society of Clinical Oncology and European Society for Medical Oncology meeting libraries from inception to November 2019. Regarding survival and tolerability, randomized controlled trials comparing different adjuvant systemic regimens against high-risk stage 2 and stage 3 colon cancer were eligible. Disease-free survival was primary endpoint. Network calculation was based on a random-effects model, and relative ranking of each node was numerically indicated by score.

Results: A total of 30 trials were included, corresponding to 54,109 patients. Regarding disease-free survival, none of the analyzed regimens displayed significant superiority against common comparator 6-month capecitabine plus oxaliplatin (XELOX), while 12-month [network hazard ratio (HR) 0.81 (0.60-1.10); 0.79 (0.57-1.10)] and 3-month XELOX [0.95 (0.86-1.04); 0.93 (0.83-1.05)] were top-ranking regimens showing non-inferiority among overall and stage 3 patients. Moreover, by pairwise meta-analysis, 3-month XELOX demonstrated significant superiority against 6-month XELOX among low-risk stage 3 patients [pairwise HR 0.78 (0.63-0.97)]. Concerning adverse events, 3-month oxaliplatin-based chemotherapy was significantly better than the 6-month counterpart with respect to peripheral sensory neuropathy, thrombocytopenia and fatigue. The 12-month capecitabine monotherapy failed to display non-inferiority among other major adverse events.

Conclusions: The 3-month XELOX treatment could be an alternative option of the 6-month regimen among low-risk stage 3 patients. Among high-risk stage 3 patients, 6-month oxaliplatin-based regimens still seem more competitive. In addition, clinical application of 12-month capecitabine monotherapy should be cautious, despite its top rankings, especially among non-Asian countries.
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http://dx.doi.org/10.1177/1758835920974195DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7739130PMC
December 2020

RYGB increases postprandial gastric nesfatin-1 and rapid relieves NAFLD via gastric nerve detachment.

PLoS One 2020 10;15(12):e0243640. Epub 2020 Dec 10.

Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Background: Roux-en-Y gastric bypass (RYGB) could reduce nonalcoholic fatty liver disease (NAFLD) ahead of the weight-loss effects. But the detailed mechanisms remain unclear.

Material And Methods: A high-fat diet (HFD) was fed to induce obesity. RYGB was then performed. Gastric nesfatin-1 was measured by enzyme-linked immunosorbent assay (ELISA) in portal vein and polymerase chain reaction (PCR) in gastric tissues. Modified surgeries including vagus-preserved bypass and vagectomy were performed and postprandial gastric nesfatin-1 were analyzed. The effects of nesfatin-1 on hepatocytes were studied by PCR and immunohistochemistry. Both intraperitoneal and intracerebroventricular injection (ICV) were performed to analyze the in vivo effects on liver lipid metabolism.

Results: Increased postprandial portal vein nesfatin-1 was observed in RYGB but not in control groups. This increase is mainly due to induction of gastric nesfatin-1. A modified RYGB in which the gastric vagus is preserved is conducted and, in this case, this nesfatin-1 induction effect is diminished. Mere vagectomy could also induce a similar nesfatin-1 increase pattern. The infusion of nesfatin-1 in the brain could inhibit the expression of gastric nesfatin-1, and the effects are diminished after gastric vagectomy. In vivo and in vitro nesfatin-1 stimulation in the liver resulted in improvements in lipid metabolism.

Conclusions: Severing the gastric vagus during RYGB could cut off the negative control from the central nervous system (CNS) and result in increased postprandial gastric nesfatin-1 post surgery, which in turn, improves NAFLD.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0243640PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7728189PMC
February 2021

Comment on "Telemedicine for Surgical Consultations- Pandemic Response or Here to Stay?: A Report of Public Perceptions.": Strategies for Telemedicine Services of General Surgery in the Post-COVID-19 Era-Experiences from Frontline Surgeons in Wuhan.

Ann Surg 2020 Nov 17. Epub 2020 Nov 17.

Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China Department of Clinical Laboratory, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.

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http://dx.doi.org/10.1097/SLA.0000000000004515DOI Listing
November 2020

IDO-inhibitor potentiated immunogenic chemotherapy abolishes primary tumor growth and eradicates metastatic lesions by targeting distinct compartments within tumor microenvironment.

Biomaterials 2021 Feb 17;269:120388. Epub 2020 Sep 17.

Research Center for Tissue Engineering and Regenerative Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China; Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. Electronic address:

Immunogenic chemotherapy (IC) is a type of chemotherapy where certain chemodrugs induce immunogenic cancer cell death (ICD), which in turn arouses T cell antitumor immunity. However, IC concurrently upregulates a key immune suppressor, indoleamine-2,3-dioxygenase (IDO), in both cancer cells and immune cells. IDO-mediated immunosuppression significantly offsets IC's therapeutic benefits in cancer patients, suggesting a necessity of combination with IDO inhibitors. Here, we report an enzyme-, pH-, and redox-triple-sensitive nanosystem using mesoporous silica nanoparticles (MSNs) as a core encapsulating doxorubicin (DOX, an immunogenic chemodrug); the core is coated with a shell (β-CD-PEI/Ge1MT) for co-delivering 1-methyl-D-tryptophan (1 MT, an IDO inhibitor). By using these responsivenesses sequentially triggering the release of 1 MT into tumor extracellular compartment and DOX into intracellular endo/lysosomal compartment, this nanosystem (DOX@GMTMSNs) precisely delivers the drugs to their target cells residing in different compartments. Released 1 MT uptake by IDO-expressing dendritic cells (DCs) and cancer cells suppresses IDO activity, reducing immunosuppressive Tregs' presence; DOX unloaded within cancer cells induces ICD, promoting effector T-cell infiltration. In two preclinical cancer models, DOX@GMTMSNs potentiate both tumor local and systemic antitumor immunity, suppressing primary tumor growth by 78% with an 83% reduction in metastatic foci, as well as extending animal survival, thus strongly demonstrating DOX@ GMTMSNs' clinical translational potential.
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http://dx.doi.org/10.1016/j.biomaterials.2020.120388DOI Listing
February 2021

Comment on "COVID-19 Outbreak and Surgical Practice: Unexpected Fatality in Perioperative Period": Challenges and strategies for General Surgery Departments During Post-COVID-19 Era in Wuhan: Experiences and Recommendations From the Frontline.

Ann Surg 2020 Oct 14. Epub 2020 Oct 14.

Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China Department of Clinical Laboratory, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

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http://dx.doi.org/10.1097/SLA.0000000000004381DOI Listing
October 2020

A Sequentially Responsive Nanosystem Breaches Cascaded Bio-barriers and Suppresses P-Glycoprotein Function for Reversing Cancer Drug Resistance.

ACS Appl Mater Interfaces 2020 Dec 24;12(49):54343-54355. Epub 2020 Nov 24.

Research Center for Tissue Engineering and Regenerative Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.

Cancer chemotherapy is challenged by multidrug resistance (MDR) mainly attributed to overexpressed transmembrane efflux pump P-glycoprotein (P-gp) in cancer cells. Improving drug delivery efficacy while co-delivering P-gp inhibitors to suppress drug efflux is an often-used nanostrategy for combating MDR, which is however challenged by cascaded bio-barriers en route to cancer cells and P-gp inhibitors' adverse effects. To effectively breach the cascaded bio-barriers while avoiding P-gp inhibitors' adverse effects, a stealthy, sequentially responsive doxorubicin (DOX) delivery nanosystem (RCMSNs) is fabricated, composed of an extracellular-tumor-acidity-responsive polymer shell (PEG--PLLDA), pH/redox dual-responsive mesoporous silica nanoparticle-based carriers (MSNs-SS-Py), and cationic β-cyclodextrin-PEI (CD-PEI) gatekeepers. The PEG--PLLDA corona makes RCMSNs stealthy with prolonged blood circulation time. Once tumors are reached, extracellular acidity degrades PEG--PLLDA, reversing nanosystem's surface charges to be positive, which drastically improves RCMSNs' tumor accumulation, penetration, and cellular internalization. Within cancer cells, CD-PEI gatekeepers detach to allow DOX unloading in response to intracellular acidity and glutathione and functionally act as a P-gp inhibitor, dampening P-gp's efflux activity by impairing ATP production. Thus, the resultant high-efficacy drug delivery along with reduced P-gp function cooperatively reverses MDR . Importantly, in preclinical tumor models, DOX@RCMSNs potently suppress MDR tumor growth without eliciting systemic toxicity, demonstrating their potential of clinical translation.
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http://dx.doi.org/10.1021/acsami.0c13852DOI Listing
December 2020

A disintegrin and metalloproteinase 8 induced epithelial-mesenchymal transition to promote the invasion of colon cancer cells via TGF-β/Smad2/3 signalling pathway.

J Cell Mol Med 2020 11 20;24(22):13058-13069. Epub 2020 Sep 20.

Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

A disintegrin and metalloproteinase 8 (ADAM8) protein is a multi-domain transmembrane glycoprotein which involves in extracellular matrix remodelling, cell adhesion, invasion and migration. ADAM8 and epithelial-mesenchymal transition (EMT) play an important role in tumour invasion has been well established. However, the interaction between ADAM8 and EMT has remained unclear. The data of colon cancer patients obtained from TCGA (The Cancer Genome Atlas) and GTEx (Genotype-Tissue Expression Project) were analysed by the bioinformatics research method. The expression of ADAM8 in colon cancer cells was up-regulated and down-regulated by transfecting with the expression plasmid and small interfering RNA, respectively. Transwell invasion assay, immunohistochemistry, immunocytochemistry, Western blotting and qRT-PCR were utilized to study the effect of ADAM8 on colon cancer cell's EMT and its related mechanisms. Analysis of TCGA and GTEx data revealed that ADAM8 was linked to poor overall survival in colon cancer patients. Besides, ADAM8 was correlated with multiple EMT biomarkers (E-cadherin, N-cadherin, Vimentin, Snail2 and ZEB2). In vitro, we also proved that the up-regulation of ADAM8 could promote EMT effect and enhance the invasive ability of colon cancer cells. On the contrary, the down-regulation of ADAM8 in colon cancer cells attenuated these effects above. Further studies suggested that ADAM8 modulated EMT on colon cancer cells through TGF-β/Smad2/3 signalling pathway. Our research suggested that ADAM8 could be a potential biomarker for the prognosis of colon cancer and induced EMT to promote the invasion of colon cancer cells via activating TGF-β/Smad2/3 signalling pathway.
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http://dx.doi.org/10.1111/jcmm.15907DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7701584PMC
November 2020

Sericin microparticles enveloped with metal-organic networks as a pulmonary targeting delivery system for intra-tracheally treating metastatic lung cancer.

Bioact Mater 2021 Jan 22;6(1):273-284. Epub 2020 Aug 22.

Research Center for Tissue Engineering and Regenerative Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.

Chemotherapy is one of the major approaches for the treatment of metastatic lung cancer. However, systemic chemotherapy is limited by poor therapeutic efficiency and severe toxic side effects, due to the extremely low delivery efficacy and non-specificity of anticancer drugs. Herein, we report a sericin microparticles enveloped with metal-organic networks as a pulmonary delivery system for treating lung metastasis of breast cancer in an animal model. The sericin microparticles (SMPs) were prepared using water in oil (w/o) emulsification method. After doxorubicin (DOX) loading, tannic acid (TA)/ferric irons (Fe) based metal organic networks (MON) were coated on the particles to obtain DOX-loaded microparticles (DOX@SMPs-MON). The SMPs-MON with good biocompatibility could effectively encapsulate DOX and sustainably unload cargos in a pH-dependent manner. The DOX-loaded microparticles could be uptaken by 4T1 cells, and effectively kill the cancer cells. In vivo, DOX@SMPs-MON was deposited in the lungs and remained for over 5 days after pulmonary administration. In contrast to conventional DOX treatment that did not show significantly inhibitory effects on lung metastatic tumor, DOX@SMPs-MON markedly decreased the number and size of metastatic nodules in lungs, and the lung weight and appearance were similar to those of healthy mice. In summary, the sericin microparticles with MON wrapping might be a promising pulmonary delivery system for treating lung metastatic cancer.
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http://dx.doi.org/10.1016/j.bioactmat.2020.08.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7451883PMC
January 2021

Strategies for perioperative management of general surgery in the post-COVID-19 era: experiences and recommendations from frontline surgeons in Wuhan.

Br J Surg 2020 Sep 4;107(10):e437. Epub 2020 Aug 4.

Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

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http://dx.doi.org/10.1002/bjs.11886DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7436704PMC
September 2020

Comment on "Approaching Surgical Triage During the COVID-19 Pandemic": Triage Outpatients of Surgical Departments for Hospitalization During Post-COVID-19 Era-Experience and Recommendations From Frontline Surgeons in Wuhan.

Ann Surg 2020 Jul 24. Epub 2020 Jul 24.

Department of Clinical Laboratory, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.

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http://dx.doi.org/10.1097/SLA.0000000000004290DOI Listing
July 2020

Field evaluation of spray drift and environmental impact using an agricultural unmanned aerial vehicle (UAV) sprayer.

Sci Total Environ 2020 Oct 29;737:139793. Epub 2020 May 29.

Shandong Provincial Engineering Technology Research Center for Agricultural Aviation Intelligent Equipment, College of Agricultural Engineering and Food Science, Shandong University of Technology, Zibo 255022, China; National Center for International Collaboration Research on Precision Agricultural Aviation Pesticides Spraying Technology (NPAAC), College of Electronic Engineering, South China Agricultural University, Guangzhou 510642, China; Department of Biological and Agricultural Engineering, Texas A&M University, College Station, TX 77845, USA. Electronic address:

Unmanned Aerial Vehicle (UAV) applications at low-volume using fine and very fine size droplets have been adopted in several commercial spray scenarios allowing water-saving and high-efficiency operation in delivery of pesticides. However, spray drift associated with UAV applications, especially for fine droplets generated from spinning disk nozzles, has not been fully understood, raising environmental and regulatory concerns. The objectives of this study were to compare the drift potential of three different volume median diameter (VMD, or Dv) of 100, 150 and 200 μm from a commercial quadcopter equipped with centrifugal nozzles exposed to different wind speeds under field conditions. Prior to field test, the droplet size of the centrifugal nozzle was measured by a laser-diffraction particle-size analyzer. The results showed that the relationship between rotation speed and Dv agrees with the negative power function. Field tests found that the deposition at 12 m downwind direction decreased by an order of magnitude compared with the average deposition within the in-swath zone. The deposition of almost all the treatments at 50 m downwind is lower than the detection limits of 0.0002 μL/cm. Based on the results from this study, the drift distance of this specific very popular UAV model is much less than that of manned aerial applicators. Based on the predicted equation (R = 0.83), the detected drift amount increased with increasing wind speed and decreasing Dv. This work provides basic information to quantify the effect of wind speeds and droplet sizes on UAV spray drift potential which supports on-going regulatory guideline development for spray buffer zone and drift risk assessment protocols.
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http://dx.doi.org/10.1016/j.scitotenv.2020.139793DOI Listing
October 2020

DNA methylation profiling to predict overall survival risk in gastric cancer: development and validation of a nomogram to optimize clinical management.

J Cancer 2020 27;11(15):4352-4365. Epub 2020 Apr 27.

Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.

DNA methylation has been reported to serve an important role in the carcinogenesis and development of gastric cancer. Our aim was to systematically develop an individualized prediction model of the survival risk combing clinical and methylation factors in gastric cancer. A univariate Cox proportional risk regression analysis was used to identify the prognosis-associated methylation sites based on the differentially expressed methylation sites between early and advanced gastric cancer group, then we applied least absolute shrinkage and selection operator (LASSO) Cox regression model to screen candidate methylation sites. Subsequently, multivariate Cox proportional risk regression analysis was conducted to identify predictive signature according to the candidate sites. Relative operating characteristic curve (ROC) analysis manifested that an 11-methylation signature exhibited great predictive efficiency for 1-, 3-, 5-year survival events. Patients in the low-risk group classified according to 11-methylation signature-based risk score yield significantly better survival than that in high-risk group. Moreover, Cox regression analysis combing methylation-based risk score and other clinical factors indicated that 11-methylation signature served as an independent risk factor. The predictive value of risk score was validated in the testing dataset. In addition, a nomogram was constructed and the ROC as well as calibration plots analysis demonstrated the good performance and clinical application of the nomogram. In conclusion, the result suggested the 11-DNA methylation signature may be potentially independent prognostic marker and functioned as a significant tool for guiding the clinical prediction of gastric cancer patients' overall survival.
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http://dx.doi.org/10.7150/jca.44436DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7255367PMC
April 2020

Safety and feasibility of prolonged versus early laparoscopic cholecystectomy for acute cholecystitis: a single-center retrospective study.

Surg Endosc 2021 May 22;35(5):2297-2305. Epub 2020 May 22.

Department of Emergency Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, 430022, Hubei, People's Republic of China.

Background: Laparoscopic cholecystectomy (LC) is the standard treatment for acute cholecystitis (AC), and it should be performed within 72 h of symptoms onset if possible. In many undesired situations, LC was performed beyond the golden 72 h. However, the safety and feasibility of prolonged LC (i.e., performed more than 72 h after symptoms onset) are largely unknown, and therefore were investigated in this study.

Methods: We retrospectively enrolled the adult patients who were diagnosed as AC and were treated with LC at the same admission between January 2015 and October 2018 in an emergency department of a tertiary academic medical center in China. The primary outcome was the rate and severity of adverse events, while the secondary outcomes were length of hospital stay and costs.

Results: Among the 104 qualified patients, 70 (67.3%) underwent prolonged LC and 34 (32.7%) underwent early LC (< 72 h of symptom onset). There were no differences between the two groups in mortality rate (none for both), conversion rates (prolonged LC 5.4%, and early LC 8.8%, P = 0.68), intraoperative and postoperative complications (prolonged LC 5.7% and early LC 2.9%, P ≥ 0.99), operation time (prolonged LC 193.5 min and early LC 198.0 min, P = 0.81), and operation costs (prolonged LC 8,700 Yuan, and early LC 8,500 Yuan, P = 0.86). However, the prolonged LC was associated with longer postoperative hospitalization (7.0 days versus 6.0 days, P = 0.03), longer total hospital stay (11.0 days versus 8.0 days, P < 0.01), and subsequently higher total costs (40,400 Yuan versus 31,100 Yuan, P < 0.01).

Conclusions: Prolonged LC is safe and feasible for patients with AC for having similar rates and severity of adverse events as early LC, but it is also associated with longer hospital stay and subsequently higher total cost.
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http://dx.doi.org/10.1007/s00464-020-07643-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8057981PMC
May 2021

Dual-engineered, "Trojanized" macrophages bio-modally eradicate tumors through biologically and photothermally deconstructing cancer cells in an on-demand, NIR-commanded, self-explosive manner.

Biomaterials 2020 08 9;250:120021. Epub 2020 Apr 9.

Research Center for Tissue Engineering and Regenerative Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China; Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. Electronic address:

To engineer tumor-tropic cells as drug delivery vehicles is a promising strategy to improve therapeutic specificity and efficacy for cancer treatment. However, conventional genetically engineered cell-based drug delivery systems are often capable of initiating single-mode therapy, and lack precise spatiotemporal control over the release of therapeutic payloads at tumor local, thus possibly causing severe systemic toxicity. Here, the macrophages are genetically engineered to encode a non-secreted form of EGFP-TNFα fusion protein and intracellularly carry near-infrared (NIR)-responsive heat-nanogenerators (HIMs). Owing to macrophages' intrinsic tumor tropism and HIMs' photo-responsiveness to NIR, these macrophages (HIMs@eM) can actively accumulate at tumor sites and undergo controlled photothermolysis induced by NIR-induced HIMs-mediated photothermal effects (PTE). Such heat-induced cell explosion enables spatiotemporally controlled release of non-secreted TNFα from macrophages and effectively kills cancer cells. Importantly, in a preclinical tumor model, HIMs@eM actively migrate to tumors where PTE and released EGFP-TNFα exhibit an enhanced antitumor effect, suppressing tumor growth and significantly prolonging animal survival without eliciting adverse side effects. Thus, this study demonstrates the potential of such dual-engineered macrophages in bi-modal cancer therapy.
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http://dx.doi.org/10.1016/j.biomaterials.2020.120021DOI Listing
August 2020

Endoscopic diagnosis and treatment of complete anastomosis stenosis after colorectal resection without protective ileostomy: report of two cases and literature review.

J Int Med Res 2020 Apr;48(4):300060520914833

Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China.

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http://dx.doi.org/10.1177/0300060520914833DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7153199PMC
April 2020

Ursodeoxycholyl lysophosphatidylethanolamide protects against hepatic ischemia/reperfusion injury via phospholipid metabolism-mediated mitochondrial quality control.

FASEB J 2020 05 12;34(5):6198-6214. Epub 2020 Mar 12.

Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Mitochondrial dysfunction is the leading cause of reactive oxygen species (ROS) burst and apoptosis in hepatic ischemia/reperfusion (I/R) injury. Ursodeoxycholyl lysophosphatidylethanolamide (UDCA-LPE) is a hepatotargeted agent that exerts hepatoprotective roles by regulating lipid metabolism. Our previous studies have shown that UDCA-LPE improves hepatic I/R injury by inhibiting apoptosis and inflammation. However, the role of UDCA-LPE in lipid metabolism and mitochondrial function in hepatic I/R remains unknown. In the present study, we investigated the role of UDCA-LPE in hepatic I/R by focusing on the interface of phospholipid metabolism and mitochondrial homeostasis. Livers from 28-week-old mice, primary hepatocytes and HepG2 cells were subjected to in vivo and in vitro I/R, respectively. Analyses of oxidative stress, imaging, ATP generation, genetics, and lipidomics showed that I/R was associated with mitochondrial dysfunction and a reduction in phospholipids. UDCA-LPE alleviated mitochondria-dependent oxidative stress and apoptosis and prevented the decrease of phospholipid levels. Our study found that cytosolic phospholipase A (cPLA ), a phospholipase that is activated during I/R, hydrolyzed mitochondrial membrane phospholipids and led to mitochondria-mediated oxidative stress and apoptosis. UDCA-LPE inhibited the interaction between cPLA and mitochondria and reduced phospholipid hydrolysis-mediated injury. UDCA-LPE might regulate the crosstalk between the phospholipid metabolism and the mitochondria, restore mitochondrial function and ameliorate I/R injury.
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http://dx.doi.org/10.1096/fj.201902013RRRDOI Listing
May 2020

SPIB promotes anoikis resistance via elevated autolysosomal process in lung cancer cells.

FEBS J 2020 11 24;287(21):4696-4709. Epub 2020 Mar 24.

Department of Immunology, Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University, China.

Anoikis (detachment-induced cell death) is a specific type of programmed cell death which occurs in response to the loss of the correct extracellular matrix connections. Anoikis resistance is an important mechanism in cancer invasiveness and metastatic behavior. Autophagy, on the other hand, involves the degradation of damaged organelles and the recycling of misfolded proteins and intracellular components. However, the intersection of these two cellular responses in lung cancer cells has not been extensively studied. Here, we identified that upon matrix deprivation, the lymphocyte lineage-specific Ets transcription factor SPIB was activated and directly enhanced SNAP47 transcription in certain lung cancer cells. Loss of attachment-induced autophagy significantly increased anoikis resistance by SPIB activation. Consistent with this function, SPIB depletion by short hairpin RNA abrogated SNAP47 transcriptional activation upon matrix deprivation. Therefore, these data delineate an important role of SPIB in autophagy-mediated anoikis resistance in lung cancer cells. Accordingly, these findings suggest that manipulating SPIB-regulated pathways in vivo and evaluating the impact of anoikis resistance warrant further investigation. DATABASE: RNA sequencing and ChIP sequencing data are available in Gene Expression Omnibus database under the accession numbers GSE106592 and GSE125561, respectively.
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http://dx.doi.org/10.1111/febs.15272DOI Listing
November 2020

Long noncoding RNA metastasis-associated lung adenocarcinoma transcript 1 cooperates with enhancer of zeste homolog 2 to promote hepatocellular carcinoma development by modulating the microRNA-22/Snail family transcriptional repressor 1 axis.

Cancer Sci 2020 May 30;111(5):1582-1595. Epub 2020 Apr 30.

Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is an oncogenic long noncoding RNA that has been found to promote carcinogenesis and metastasis in many tumors. However, the underlying role of MALAT1 in the progression and metastasis of hepatocellular carcinoma (HCC) remains unclear. In this study, aberrantly elevated levels of MALAT1 were detected in both HCC specimens and cell lines. We found that knockdown of MALAT1 caused retardation in proliferation, migration, and invasion both in vivo and in vitro. Mechanistic investigations showed that Snail family transcriptional repressor 1 (SNAI1) is a direct target of microRNA (miR)-22 and that MALAT1 modulates SNAI1 expression by acting as a competing endogenous RNA for miR-22. Inhibition of miR-22 restored SNAI1 expression suppressed by MALAT1 knockdown. Furthermore, MALAT1 facilitated the enrichment of enhancer of zeste homolog 2 (EZH2) at the promoter region of miR-22 and E-cadherin, which was repressed by MALAT1 knockdown. Cooperating with EZH2, MALAT1 positively regulated SNAI1 by repressing miR-22 and inhibiting E-cadherin expression, playing a vital role in epithelial to mesenchymal transition. In conclusion, our results reveal a mechanism by which MALAT1 promotes HCC progression and provides a potential target for HCC therapy.
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http://dx.doi.org/10.1111/cas.14372DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7226208PMC
May 2020

Correction to: IL-33 facilitates proliferation of colorectal cancer dependent on COX2/PGE.

J Exp Clin Cancer Res 2020 Jan 17;39(1):15. Epub 2020 Jan 17.

Research Center for Tissue Engineering and Regenerative Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.

In the original publication of this manuscript [1], there are three errors in Fig. 1. The identified errors do not affect the conclusions of the work.
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http://dx.doi.org/10.1186/s13046-020-1524-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6966836PMC
January 2020