Publications by authors named "Yandong Li"

99 Publications

miR-15a and miR-20b sensitize hepatocellular carcinoma cells to sorafenib through repressing CDC37L1 and consequent PPIA downregulation.

Cell Death Discov 2022 Jun 27;8(1):297. Epub 2022 Jun 27.

Department of Oncology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China.

Sorafenib is a classical targeted drug for the treatment of advanced hepatocellular carcinoma (HCC), but intrinsic resistance severely limited its therapeutic effects. In the present study, we aimed to identify crucial genes in HCC cells that affect sorafenib resistance by a CRISPR/Cas9 genome-scale screening. The results indicated that the deficiency of miR-15a and miR-20b contributed to sorafenib resistance, whereas exogenous expression of miR-15a and miR-20b enhanced sorafenib sensitivity of HCC cells by cell viability, colony formation, and flow cytometry analyses. Further analyses revealed that cell division cycle 37 like 1 (CDC37L1) as a common target of miR-15a and 20b, was negatively regulated by the two miRNAs and could enhance sorafenib resistance of HCC cells in vitro and in vivo. Mechanistically, CDC37L1, as a cochaperone, effectively increased the expression of peptidylprolyl isomerase A (PPIA) through strengthening the binding between heat shock protein 90 (HSP90) and PPIA. The results from immunohistochemical staining of a HCC tissue microarray revealed a positive association between CDC37L1 and PPIA expression, and high expression of CDC37L1 and PPIA predicted worse prognosis of HCC patients after sorafenib therapy. Taken together, our findings reveal crucial roles of miR-15a, miR-20b, CDC37L1, and PPIA in sorafenib response of HCC cells. These factors may serve as therapeutic targets and predict prognosis for HCC treated with sorafenib.
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http://dx.doi.org/10.1038/s41420-022-01094-2DOI Listing
June 2022

A Novel Classification Model for Lower-Grade Glioma Patients Based on Pyroptosis-Related Genes.

Brain Sci 2022 May 28;12(6). Epub 2022 May 28.

Clinical Molecular Medicine Testing Center, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.

Recent studies demonstrated that pyroptosis plays a crucial role in shaping the tumor-immune microenvironment. However, the influence of pyroptosis on lower-grade glioma regarding immunotherapy and targeted therapy is still unknown. This study analyzed the variations of 33 pyroptosis-related genes in lower-grade glioma and normal tissues. Our study found considerable genetic and expression alterations in heterogeneity among lower-grade gliomas and normal brain tissues. There are two pyroptosis phenotypes in lower-grade glioma, and they exhibited differences in cell infiltration characteristics and clinical characters. Then, a PyroScore model using the lasso-cox method was constructed to measure the level of pyroptosis in each patient. PyroScore can refine the lower-grade glioma patients with a stratified prognosis and a distinct tumor immune microenvironment. Pyscore may also be an effective factor in predicting potential therapeutic benefits. In silico analysis showed that patients with a lower PyroScore are expected to be more sensitive to targeted therapy and immunotherapy. These findings may enhance our understanding of pyroptosis in lower-grade glioma and might help optimize risk stratification for the survival and personalized management of lower-grade glioma patients.
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http://dx.doi.org/10.3390/brainsci12060700DOI Listing
May 2022

A Novelly Developed Bipolar Needle Knife Can Be an Alternative Device Choice for Endoscopic Submucosal Dissection (With Video).

Front Med (Lausanne) 2022 13;9:888635. Epub 2022 May 13.

Department of Endoscopy, Institute of Basic Medicine and Cancer (IBMC), Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Chinese Academy of Sciences, Hangzhou, China.

Background: Endoscopic submucosal dissection (ESD) is technically difficult with high rates of complications, such as perforation and bleeding. We aimed to explore the safety and cutting efficiency of a novelly devised bipolar knife for ESD procedure.

Methods: Taking a traditional monopolar knife as a reference, the safety and feasibility of the novel bipolar knife were evaluated by an animal experiment and a human study. Furthermore, we assessed the usefulness and advantage of this novel bipolar knife by using the finite element method.

Results: A porcine experiment confirmed that there was no significant difference in wound size and cutting speed between the monopolar and bipolar knives. The thermal damage and histopathological scores produced by the two knives were similar. In addition, the porcine experiment and patients' study identified that the incidence of postoperative complications, such as bleeding, perforation, and infection, had no statistical difference between the monopolar and bipolar groups. Finally, the finite element model showed that the length and depth of thermal damage caused by the bipolar knife were, respectively, 102.77-117.98% and 80.87-84.53% of those caused by the monopolar knife at the same power.

Conclusion: The novel bipolar knife was theoretically safer than the monopolar knife and, at least, was confirmed not inferior to the monopolar knife in operability and cutting efficiency. Thus, the novel bipolar knife can be an alternative device choice for ESD.
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http://dx.doi.org/10.3389/fmed.2022.888635DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9136242PMC
May 2022

Effect of lentivirus-mediated peroxiredoxins 6 gene silencing on the phenotype of human gastric cancer BGC-823 cells.

J Cancer Res Ther 2022 Apr;18(2):411-417

Pharmacy College of Beihua University, Jilin, Jilin, P. R. China.

Aims: Peroxiredoxins (PRDX6) regulates the occurrence and progression of cancer. The aim of this study is to investigate the effect of PRDX6 knockdown on the biological behavior of human gastric cancer cell line BGC-823 cells.

Settings And Design: Research article.

Subjects And Methods: The differential expression of PRDX6 in gastric cancer and normal gastric tissues was tested by immunohistochemistry. Ribonucleic acid plasmid of PRDX6 gene was packaged using a lentivirus, and BGC-823 cells were transfected with the lentivirus to obtain a BGC-823 cell line in which the expression of PRDX6 was stably silenced.

Statistical Analysis Used: The proliferation activity of BGC-823 cells was detected using the cell counting kit-8 method. The effect of PRDX6 on the migration and invasion of BGC-823 cells was evaluated using the scratch test and Transwell assay, and the expression of related proteins was detected by western blot.

Results: The expression of PRDX6 in gastric cancer was significantly increased (P < 0.05). Compared with those in the untransfected and negative control groups. The proliferation, migration, and invasion of gastric cancer BGC-823 cells were significantly inhibited, and the apoptotic rates were significantly increased in the lentivirus-transfected (short hairpin-PRDX6) group. Western blot analysis showed that the expression of Bax protein increased, whereas that of proliferating cell nuclear antigen, Bcl-2, PI3K, phospho (p-Akt), and phosphorylated-mammalian target of rapamycin (mTOR) decreased significantly compared with that in WT and vector groups (P < 0.05).

Conclusion: The knockdown of PRDX6 gene expression in BGC-823 cells can inhibit the proliferation, migration, and invasion of gastric cancer cells and promote apoptosis, thereby affecting gastric cancer cells.
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http://dx.doi.org/10.4103/jcrt.jcrt_1083_21DOI Listing
April 2022

UHMK1 aids colorectal cancer cell proliferation and chemoresistance through augmenting IL-6/STAT3 signaling.

Cell Death Dis 2022 May 2;13(5):424. Epub 2022 May 2.

Department of Oncology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China.

UHMK1, a serine/threonine kinase with a U2AF homology motif, is implicated in RNA processing and protein phosphorylation. Increasing evidence has indicated its involvement in tumorigenesis. However, it remains to be elucidated whether UHMK1 plays a role in the development of colorectal cancer (CRC). Here, we demonstrated that UHMK1 was frequently upregulated in CRC samples compared with adjacent normal tissue and high expression of UHMK1 predicted poor outcomes. Knockdown of UHMK1 by siRNAs restrained CRC cell proliferation and increased oxaliplatin sensitivity, whereas overexpression of UHMK1 promoted CRC cell growth and oxaliplatin resistance, suggesting that UHMK1 plays important oncogenic roles in CRC. Mechanistically, we showed that UHMK1 had a significant effect on IL6/STAT3 signaling by interacting with STAT3. The interaction of UHMK1 with STAT3 enhanced STAT3 activity in regulating gene transcription. Furthermore, we found that STAT3 could in turn transcriptionally activate UHMK1 expression in CRC cells. The complementary experiments for cell growth and oxaliplatin resistance indicated the interdependent relationship between UHMK1 and STAT3. Thus, these collective findings uncovered a new UHMK1/STAT3 positive feedback regulatory loop contributing to CRC development and chemoresistance.
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http://dx.doi.org/10.1038/s41419-022-04877-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9061793PMC
May 2022

Landscape and perspectives of macrophage -targeted cancer therapy in clinical trials.

Mol Ther Oncolytics 2022 Mar 22;24:799-813. Epub 2022 Feb 22.

National Central Cancer Registry, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.

Tumor-associated macrophages (TAMs) exert integrated effects in all aspects of tumor progression, including tumor cell proliferation, angiogenesis, invasion, and metastasis. Recently, considerable preclinical and clinical trials have demonstrated that TAM-targeted therapy is an effective antitumor therapeutic approach, especially as a complementary strategy in combination with conventional chemotherapy, radiotherapy, or emerging immunotherapy. Here, we review all of the current clinical trials targeting TAMs worldwide up to May 2021 and highlight instances of the synergetic therapeutic efficacy of TAM-targeted combined therapeutic strategies. In total, 606 clinical trials were conducted, including 143 tested products. There has been explosive growth in macrophage-targeted therapy around the world during the past decade. Most trials were at early phase, and two-thirds used macrophage-targeting therapy as part of a combination approach. The most common combination is that of traditional chemotherapy with TAM-targeted therapy, followed by immune checkpoint inhibitors and targeted drugs. TAM-targeted therapeutic approaches are a newly emerging but rapidly developing area of anticancer therapy, especially as a combinatorial therapeutic approach. Further investigation of promising combination strategies will pave the way to more effective anticancer therapies.
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http://dx.doi.org/10.1016/j.omto.2022.02.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8908037PMC
March 2022

TNFAIP3 alleviates pain in lumbar disc herniation rats by inhibiting the NF-κB pathway.

Ann Transl Med 2022 Jan;10(2):80

Department of Surgery, Shuguang Hospital, Zhangye, China.

Background: It's been reported that the tumor necrosis factor alpha inducible protein 3 () gene played an important role in the pathogenesis of autoimmune and chronic inflammation diseases. Moreover, in degenerative diseases of the lumbar spine the nuclear factor-κB (NF-κB) pathway is significantly activated. This study aimed to explore the role of the tumor necrosis protein-induced zinc finger protein A20 (A20) protein in degenerative diseases of the lumbar spine on the NF-κBp65 pathway.

Methods: A total of 96 rats were randomly divided into 4 groups. Lumbar disc herniation (DH) was set as a sham operation group (Sham group), DH + A20 group and DH + control group (Control group); measured changes in rat paw withdrawal threshold (PWT) and paw withdrawal latency (PWL); detected the proportion of apoptotic cells in a single nucleus pulposus cell suspension, analyzed the correlation between tumor necrosis factor-α (TNF-α) content and pain in DH rats, and the expression changes of NF-κB pathway in nucleus pulposus tissue.

Results: compared with the DH + Control group, the PWT and PWL of the DH + A20 group increased significantly (P<0.05); apoptosis in the DH + A20 group was significantly reduced (P<0.01); the nucleus pulposus tissue and serum levels of TNF-α and interleukin-6 (IL-6) in the DH + A20 rat group were significantly lower than those in the DH + Control group (P<0.05); the protein expression of rats in the DH + A20 group (p-p65) was significantly lower than that in the DH + Control group (P<0.05).

Conclusions: The pain of lumbar disc herniation rats is related to TNF-α, and overexpression of A20 protein can reduce the pain of lumbar disc herniation by inhibiting the NF-κB pathway.

Keywords: Lumbar disc herniation (lumbar DH); tumor necrosis factor-α (TNF-α); interleukin-6 (IL-6); tumor necrosis factor alpha inducible protein 3 (TNFAIP3).
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http://dx.doi.org/10.21037/atm-21-6499DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8848453PMC
January 2022

Analysis of Behaviors of the Railway Subgrade with a New Waterproof Seal Layer.

Materials (Basel) 2022 Feb 3;15(3). Epub 2022 Feb 3.

School of Civil Engineering, Southwest Jiaotong University, Chengdu 610031, China.

This study proposes a new waterproof sealing layer to reduce the impact of water on subgrade beds. The proposed waterproof sealing layer is composed of a polyurethane adhesive (PA) mixture, which aims to control interlaminar deformation and prevent seepage. A variety of laboratory tests were first performed to analyze the attenuation characteristics and mechanical properties of various polyurethane polymer (PP)-improved gravel mixtures under thermohydraulic coupling effects. In addition, a waterproof performance model test of the PP-improved gravel layer was conducted to investigate its waterproof and drainage performance and hydraulic damage mechanism. Finally, the feasibility and effectiveness of the surface structure of the waterproof drainage subgrade bed containing the PA mixture was tested in combination with the treatment project of the Ciyaowan station of the Baoshen heavy-haul railway. According to the experimental and model results, (1) the waterproof layer containing the polyurethane mixture exhibited satisfactory stiffness, elasticity and flexibility. The waterproof layer containing the polyurethane mixture also controlled the deformation between layers, and its mechanical properties remained stable. (2) The waterproof layer with the dense polyurethane mixture performed well in terms of the waterproof aspect, and no infiltration occurred under cyclic load (3). Long-term field monitoring revealed that the effect of the implementation of a PP-improved gravel layer to treat mud pumping was remarkable. The settlement of the PP-improved gravel layer only reached 13.21 mm, and the settlement remained stable in the later stage.
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http://dx.doi.org/10.3390/ma15031180DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8838606PMC
February 2022

CEA-regulated Oncolytic Virus Anticancer Therapy: A Promising Strategy for Rare Solid Tumors.

Curr Cancer Drug Targets 2022 ;22(2):126-132

National Cancer Center, Cancer Hospital of Chinese Academy of Medical Sciences, Beijing, China.

Background: Rare solid tumors have attracted much more attention due to the great unmet clinical need, limited treatment options, and poor prognosis. As the most thoroughly studied tumor marker, carcinoembryonic antigen (CEA) can not only overexpress in various common solid tumors but also in several rare solid tumors. Oncolytic virus therapy has achieved excellent anticancer effects in the past decades. Due to the specific high expression of CEA in certain tumor tissues but not in normal tissues, CEA has been applied to improve the tumor specificity of gene expression.

Methods: The studies of CEA expression in rare solid tumors and CEA-regulated oncolytic virus therapy were reviewed.

Results: We showed the types of rare solid tumors with the overexpression of CEA. Elevated serum CEA levels can indicate the diagnosis, response of surgery or system therapy, distal metastasis, recurrence, and survival. Due to high tumor specificity, CEA-regulated OA therapy has demonstrated a surprising antitumor effect for common CEA-positive tumors in preclinical trials.

Conclusion: These data suggested that CEA could be a diagnostic and prognostic biomarker for several rare solid tumors. We proposed the hypothesis that CEA-regulated oncolytic virus therapy could be a promising therapeutic strategy for CEA-positive rare solid tumors.
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http://dx.doi.org/10.2174/1568009622666220202143852DOI Listing
January 2022

"Pink Pattern" Visualized in Magnifying Endoscopy With Narrow-Band Imaging Is a Novel Feature of Early Differentiated Gastric Cancer: A Bridge Between Endoscopic Images and Histopathological Changes.

Front Med (Lausanne) 2021 15;8:763675. Epub 2021 Nov 15.

Department of Endoscopy, Zhejiang Cancer Hospital, Institute of Cancer and Basic Medicine, University of Chinese Academy of Sciences, Hangzhou, China.

A pink color change occasionally found by us under magnifying endoscopy with narrow-band imaging (ME-NBI) may be a special feature of early gastric cancer (EGC), and was designated the "pink pattern". The purposes of this study were to determine the relationship between the pink pattern and the cytopathological changes in gastric cancer cells and whether the pink pattern is useful for the diagnosis of EGC. The color features of ME-NBI images and pathological images of cancerous gastric mucosal surfaces were extracted and quantified. The cosine similarity was calculated to evaluate the correlation between the pink pattern and the nucleus-to-cytoplasm ratio of cancerous epithelial cells. Two diagnostic tests were performed by 12 endoscopists using stored ME-NBI images of 185 gastric lesions to investigate the diagnostic efficacy of the pink pattern for EGC. The diagnostic values, such as the area under the curve (AUC), the accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), of test 1 and test 2 were compared. The cosine similarity between the color values of ME-NBI images and pathological images of 20 lesions was at least 0.744. The median AUC, accuracy, sensitivity, specificity, PPV, and NPV of test 2 were significantly better than those of test 1 for all endoscopists and for the junior and experienced groups. The pink pattern observed in ME-NBI images correlated strongly with the change in the nucleus-to-cytoplasm ratio of gastric epithelial cells, and could be considered a useful marker for the diagnosis of differentiated EGC.
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http://dx.doi.org/10.3389/fmed.2021.763675DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8634361PMC
November 2021

Equilibrium Phase Relations of a SiO-AlO-FeO System with 10 wt % CaO Addition for the Production of Continuous Basalt Fibers.

ACS Omega 2021 Aug 13;6(33):21465-21471. Epub 2021 Aug 13.

School of Material Science and Engineering, Northeastern University, Shenyang, Liaoning 110819, P. R. China.

The continuous basalt fibers have been regarded as one of the most promising green materials in modern society; however, key thermodynamic equilibrium data are insufficient for a better understanding of the crystallization mechanism during the fiber forming process. In the present study, the equilibrium phase relations of the core SiO-AlO-FeO subsystem with fixed 10 wt % CaO were experimentally determined using the classic equilibrium-quenching technique with the scanning electron microscopy-energy-dispersive X-ray spectroscopy analysis. All samples were presented as liquid-silica coexisting within the basalt composition range. The 1300 and 1400 °C isotherms were constructed based on the experimental results. However, significant discrepancies were confirmed with further comparison of the experimental results with FactSage predictions, indicating that more efforts are needed for the optimization of the basalt oxide-related thermodynamic databases.
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http://dx.doi.org/10.1021/acsomega.1c02287DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8388073PMC
August 2021

Genome-scale CRISPRa screening identifies MTX1 as a contributor for sorafenib resistance in hepatocellular carcinoma by augmenting autophagy.

Int J Biol Sci 2021 25;17(12):3133-3144. Epub 2021 Jul 25.

Department of Oncology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200120, China.

Sorafenib is the standard first-line drug for the treatment of advanced hepatocellular carcinoma (HCC), however, its therapeutic efficacy is not satisfactory due to primary or secondary resistance of HCC cells. In the present study, we identified Metaxin 1 (MTX1) as a new regulator of sorafenib resistance in HCC through genome-scale CRISPR activation (CRISPRa) screening. We found that MTX1 was frequently upregulated in HCC tissues and overexpression of MTX1 promoted HCC cell proliferation and . As well, MTX1 overexpression increased cell growth rate and decreased cell apoptosis upon sorafenib treatment. Consistently, the resistance induced by MTX1 was also observed in subcutaneous xenograft tumor model. Clinically, high expression of MTX1 was closely related with poor outcomes in HCC patients who received sorafenib treatment. Mechanistically, overexpression of MTX1 could promote HCC cell autophagy via interacting with and inhibiting CDGSH iron sulfur domain 1 (CISD1), an autophagy negative regulator. Taken together, our findings suggest that MTX1 is upregulated in HCC and contributes to sorafenib resistance via a possible mechanism involving CISD1 mediated autophagy.
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http://dx.doi.org/10.7150/ijbs.62393DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8375235PMC
March 2022

A Genome-Scale CRISPR Knock-Out Screen Identifies MicroRNA-5197-5p as a Promising Radiosensitive Biomarker in Colorectal Cancer.

Front Oncol 2021 30;11:696713. Epub 2021 Jul 30.

Department of Oncology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.

Radioresistance is one of the main reasons causing unsatisfactory curative effects of ionizing radiation (IR) against colorectal cancer (CRC). However, its underlying mechanisms remain unclear yet. In the present study, we applied a genome-scale CRISPR knockout screen in combination of NGS sequencing upon CRC cell lines to explore regulatory factors involved radioresistance of CRC, and 3 candidate genes were identified. Cytotoxicity of IR was determined by Cell Counting Kit-8 (CCK-8) assay, colony formation assay and apoptosis assay, and microRNA-5197-5p (miR-5197) was found to significantly enhance the cytotoxicity of IR to CRC cells. By further mechanistic investigation, we demonstrated that miR-5197 directly targeted CDK6 and inhibited its expression in RKO cells, which induced cell cycle arrest at G1/S phase and inhibited cell division, thereby radiosensitivity was enhanced by miR-5197. Our findings revealed that miR-5197 might be a critical factor regulating CRC cell radiosensitivity and provided novel insights into the development of therapeutic strategies for CRC patients who are resistant to IR.
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http://dx.doi.org/10.3389/fonc.2021.696713DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8362832PMC
July 2021

Effect of Mg Addition on the Microstructure and Properties of a Heat-Affected Zone in Submerged Arc Welding of an Al-Killed Low Carbon Steel.

Materials (Basel) 2021 May 8;14(9). Epub 2021 May 8.

School of Metallurgy, Northeastern University, Shenyang 110819, China.

To reveal the effect of Mg treatment on the microstructure evolution behavior in the actual steel welding process, the microstructure and properties of Al-deoxidized high-strength ship plate steel with Mg addition were analyzed after double-side submerged arc welding. It was found that the Al-Mg-O + MnS inclusion formed under 26 ppm Mg treatment could promote acicular ferrite (AF) nucleation in the coarse-grained heat-affected zone (CGHAZ) and inhibit the formation of widmanstätten ferrite and coarse grain boundary ferrite. In the fine-grained heat-affected zone (FGHAZ) and intercritical heat-affected zone (ICHAZ), polygonal ferrite and pearlite were dominant. Al-Mg-O+MnS cannot play a role in inducing AF, but the grain size of ferrite was refined by Mg addition. The impact toughness in HAZ of the Mg-added steel was higher than that of Mg-free steel. With the heat-input rising from 29.55 to 44.11 kJ/cm, it remained relatively stable in Mg-treated steel. From the fusion line to the base metal, the micro-hardness of the fusion zone, CGHAZ, ICHAZ and FGHAZ decreased to some extent after Mg addition, which means the cold cracking tendency in the welding weak zone could be reduced. Finally, the mechanisms of Mg-containing inclusion-induced AF were also systematically discussed.
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http://dx.doi.org/10.3390/ma14092445DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8125884PMC
May 2021

Diagnosis, treatment, and misdiagnosis analysis of 28 cases of central nervous system echinococcosis.

Chin Neurosurg J 2021 May 21;7(1):30. Epub 2021 May 21.

Department of Neurosurgery, The First Teaching Hospital of Xinjiang Medical University, Xinjiang, 830054, China.

Background: To explore central nervous system (CNS) involvement in this disease, from the perspectives of diagnosis, treatment, and misdiagnosis METHODS: Twenty-eight patients with CNS echinococcosis were included in this retrospective study, including 18 males (64.3%) and 10 (35.7%) females. The average age of all the patients were 23.5 years (ranged 4-60 years). Twenty-three (23) patients (82.1%) received the first surgical resection in our hospital. Five (5) patients (17.9%) gave up surgical treatment for multiple-organ hydatidosis and previous surgery history at other hospitals, and albendazole was applied for a long-term (3-6 months) adjunct therapy for the 5 patients. The average follow-up time was 8 years.

Results: For the 28 patients, 23 cases received surgical treatments, and the diagnosis was confirmed by pathological examinations. The diagnosis of 4 cases of brain echinococcosis and 2 cases of spinal cord echinococcosis could not be confirmed, resulting in a misdiagnosis rate of 21.4% (6/28). For the pathological examination, a total of 17 cases were infected with Echinococcus granulosus (including 2 cases of spinal cord echinococcosis), and 6 cases were infected with Echinococcus alveolaris.

Conclusion: The diagnosis should be specifically considered in endemic regions. The clinical features of CNS hydatidosis were intracranial space-occupying lesions. For the treatment, the surgical removal of cysts should be necessary. In addition, the adjuvant therapy with drug and intraoperative prophylaxis is also suggested. The misdiagnosis may have resulted from atypical clinical features and radiographic manifestations, as well as the accuracy of hydatid immunologic test.
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http://dx.doi.org/10.1186/s41016-021-00248-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8139029PMC
May 2021

CDC37L1 acts as a suppressor of migration and proliferation in gastric cancer by down-regulating CDK6.

J Cancer 2021 31;12(11):3145-3153. Epub 2021 Mar 31.

Department of Thoracic Surgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China.

The co-chaperone protein CDC37 (Cell division cycle 37) is well known to regulate multiple protein kinases and involved in tumor progression. However to date, little is known about its analogue CDC37L1 (Cell division cycle 37 like 1) in tumorigenesis. This study aimed to explore the expression and function of CDC37L1 in gastric cancer (GC). The immunohistochemical staining in a tissue microarray showed a weak expression of CDC37L1 in high grade GC tissues compared with low grade tissues. Consistently, data from online database analysis demonstrated that CDC37L1 level was decreased in stage 4 patients and low expression of CDC37L1 indicated a poor prognosis. Functional studies revealed that CDC37L1 could inhibit GC cell proliferation and migration in CCK8, EdU incorporation, colony formation and transwell assays. In the meantime, CDC37L1 also inhibited the tumorigenicity of GC cells in nude mice. Mechanistically, we found that CDC37L1 had an impact on CDK6 protein expression by western blotting. Palbociclib, a specific CDK4/6 inhibitor, was discovered to block the rapid growth phenotype of GC cells induced by CDC37L1 silencing. Taken together, these findings unveiled a tumor-suppressive role of CDC37L1 in GC, and CDK6 may act as a downstream effector in this process.
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http://dx.doi.org/10.7150/jca.56097DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100790PMC
March 2021

FOXM1-induced miR-552 expression contributes to pancreatic cancer progression by targeting multiple tumor suppressor genes.

Int J Biol Sci 2021 1;17(4):915-925. Epub 2021 Mar 1.

Department of Oncology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China.

Dysregulation of microRNAs (miRNAs) plays important roles during carcinogenesis. Forkhead box M1 (FOXM1), a well-known oncogenic transcription factor, has been implicated in the progression of multiple cancer types. To find out FOXM1-induced abnormal miRNAs in pancreatic cancer, we analyzed TCGA database and figured out miR-552 as the most relevant miRNA with FOXM1. Molecular experimental results demonstrated that FOXM1 transcriptionally activated miR-552 expression by directly binding to the promoter region of miR-552. In a pancreatic cancer tissue microarray, miR-552 expression was positively correlated with FOXM1 and high expression of miR-552 could predict poor patient outcome. Functionally, overexpression of miR-552 promoted pancreatic cancer cell migration and inhibition of miR-552 attenuated this phenotype. The inhibitory effect on cell migration caused by FOXM1 knockdown could be restored by exogenous expression of miR-552. By informatics analysis, we identified three tumor suppressor genes: DACH1, PCDH10 and SMAD4, all of which were negatively associated with FOXM1 and validated as functionally relevant targets of miR-552. Taken together, our findings provide a new FOXM1-miR-552-DACH1/PCDH10/SMAD4 axis to regulate pancreatic cancer cell progression and new opportunities for therapeutic intervention against this disease.
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http://dx.doi.org/10.7150/ijbs.56733DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040302PMC
January 2022

Response by Li et al to Letter Regarding Article, "gp130 Controls Cardiomyocyte Proliferation and Heart Regeneration".

Circulation 2021 04 12;143(15):e813-e814. Epub 2021 Apr 12.

State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

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http://dx.doi.org/10.1161/CIRCULATIONAHA.120.052610DOI Listing
April 2021

Transplantation of Neonatal Mouse Cardiac Macrophages into Adult Mice.

J Vis Exp 2021 03 20(169). Epub 2021 Mar 20.

Fuwai Hospital & Chinese Academy of Medical Sciences, State Key Laboratory of Cardiovascular Disease, Cardiovascular Institute, National Center for Cardiovascular Diseases, Peking Union Medical College; National Health Commission Key Laboratory of Cardiovascular Regenerative Medicine, Fuwai Central-China Hospital, Central-China Subcenter of National Center for Cardiovascular Diseases;

In an injured neonatal myocardium, macrophages facilitate cardiomyocyte proliferation and angiogenesis and promote heart regeneration. The present study reveals that transplantation of neonatal cardiac macrophages recruited by injury promotes adult heart regeneration after myocardial infarction with improvement of cardiac function and cardiomyocyte proliferation. The results indicate that neonatal cardiac macrophage transplantation could be a promising strategy for cardiac injury treatment. Here, we provide the technical details, including the isolation of neonatal cardiac macrophages from apical resection-injured neonatal mouse hearts, the transplantation of macrophages into myocardial-infarcted adult mice, and the estimation of heart regeneration after a macrophage graft.
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http://dx.doi.org/10.3791/62108DOI Listing
March 2021

Immunogenic Cell Death (ICD) of Murine H22 Cells Induced by Lentinan.

Nutr Cancer 2022 15;74(2):640-649. Epub 2021 Mar 15.

College of Biological Science and Engineering, Hebei University of Science and Technology, Shijiazhuang, China.

Lentinan can lead to apoptosis of tumor cells and improve immune function. However, limited research focused on the immunogenic death regulation mechanism of lentinan on mouse H22 cells. The study aimed to explore the effect of Lentinan on the expression of immunogenic death-related proteins in mice H22 cells. MTT method was used to detect and evaluate the effect of 200-1000 μg/mL lentinan on the survival rate of H22 cells after 24 h, 48 h, and 72 h, respectively. Flow cytometry was employed to collect the apoptotic rate of lentinan at different concentrations (200-800μg/mL) on H22 cells for 48 h, and obtain the apoptotic rate of 600 μg/mL lentinan at different times (12-72 h). The effect of Lentinan on the expression of H22 Immunogenic Cell Death proteins was analyzed by ELISA and HPLC-MS afterward. Results suggest that lentinan cytotoxic and pro-apoptotic have a concentration-dependent manner with the H22 cells. Moreover, the rate of apoptosis increased significantly ( < 0.05) in 24 h. Lentinan can induce the expression of Calreticulin(CRT), High mobility protein 1(HMGB1), ATP and Heat shock protein 70 (HSP70) .Therefore, the antitumor effect of lentinan may be related to the regulation of immunogenic death-related protein expression, which was beneficial to the future development of liver cancer vaccines.
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http://dx.doi.org/10.1080/01635581.2021.1897632DOI Listing
March 2022

Do we need to conduct full-thickness closure after endoscopic full-thickness resection of gastric submucosal tumors?

Turk J Gastroenterol 2020 12;31(12):942-947

The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, China.

Background/aims: Successful closure of gastric wall defects is a pivotal step for endoscopic full-thickness resection (EFTR). Our study indicates that for submucosal tumors (SMTs) smaller than 2.5 cm, closing the mucosal layer is safe and feasible when the modified method, ZIP, is used.

Materials And Methods: We retrospectively analyzed 37 patients with gastric SMTs arising from the muscularis propria (MP) who underwent EFTR with defect closure of the mucosal layer. The main procedure involved: (1) making a longitudinal incision of the mucosal and submucosal layers above the lesion, (2) fully exposing the lesion and symmetrically punching holes on both sides of the incision into the submucosal layer, (3) en bloc resection of the lesion using an electrosurgical snare or knife, (4) hooking of metallic clips into the holes and clipping of the mucosal layer successively to close the gastric wall defect. This modified method was named ZIP.

Results: Successful complete resection by EFTR was achieved in 37 cases (100%). The median procedure time was 60 min (range: 30-120 min), whereas the closure procedure took a median of 8 min (range: 5-20 min). The median lesion size was 1.0 cm (range: 0.5-2.5 cm). No patients had severe complications. No residual lesions or tumor recurrence were found during the follow-up period.

Conclusion: Closing the mucosal layer of gastric wall defects after EFTR by ZIP is feasible and effective.
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http://dx.doi.org/10.5152/tjg.2020.19685DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7928250PMC
December 2020

A Novel Bipolar Polypectomy Snare Can Be an Alternative Choice for Endoscopic Resection.

Front Med (Lausanne) 2020 20;7:619844. Epub 2021 Jan 20.

Department of Endoscopy, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Cancer and Basic Medicine (IBMC), Chinese Academy of Sciences, Hangzhou, Zhejiang, China.

Endoscopic resection (ER) is more difficult and has a higher rate of complications, such as perforation and bleeding. The aim of this study was to evaluate the safety and feasibility of a bipolar polypectomy snare for ER. Initial ER procedures in live pigs were carried out. Then, a human feasibility study was performed in patients with colorectal polyps. Finally, the finite element method was used to evaluate the safety and effectiveness of the new bipolar snare. In the live animal model, there were no significant differences in wound size and cutting time between monopolar and bipolar groups. The histological results (histological scores) of the two groups in porcine experiments were almost the same except that the incision flatness of bipolar group was better than that of the monopolar group. Incidence of bleeding and perforation was similar between the two groups in pigs' and patients' study. At last, the finite element model showed that the vertical thermal damage depth produced by bipolar snare system was approximately 71-76% of that produced by monopolar snare system at the same power. The novel bipolar snare is feasible in patients with colorectal polyps and can be an alternative choice for ERs.
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http://dx.doi.org/10.3389/fmed.2020.619844DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7855578PMC
January 2021

Overexpression of NELFE contributes to gastric cancer progression via Wnt/β-catenin signaling-mediated activation of CSNK2B expression.

J Exp Clin Cancer Res 2021 Feb 1;40(1):54. Epub 2021 Feb 1.

Department of Oncology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China.

Background: Accumulating evidence has highlighted the importance of negative elongation factor complex member E (NELFE) in tumorigenesis. However, the relationship between NELFE and gastric cancer (GC) remains unclear. This study aimed to explore the expression pattern and specific function of NELFE in GC.

Methods: NELFE expression was evaluated by immunohistochemistry and qRT-PCR in GC tissues, respectively. Cell proliferation, migration and invasion were measured by CCK-8, colony formation, transwell assays, and nude mice model. Bioinformatics analysis was performed to search potential target genes of NELFE, and a Cignal Finder 10-Pathway Reporter Array was used to explore potential signaling pathways regulated by NELFE. Dual-luciferase reporter assays, qRT-PCR and western blotting were conducted to verify their regulatory relationship. The expression correlations among NELFE, β-catenin and CSNK2B were further explored by immunohistochemistry on consecutive resections.

Results: NELFE was significantly overexpressed in GC tissues both in protein and mRNA level and negatively correlated with the prognosis of GC patients. Gain- and loss-of-function experiments showed that NELFE potentiated GC cell proliferation and metastasis in vitro and in vivo. CSNK2B was identified as a downstream effector of NELFE. Wnt/β-catenin signaling may mediate the regulation of CSNK2B by NELFE. In addition, NELFE, β-catenin and CSNK2B were all remarkably upregulated in tumor tissues compared with adjacent normal tissues, and their expression levels in GC were positively correlated with each other.

Conclusion: Our findings reveal a new NELFE-Wnt/β-catenin-CSNK2B axis to promote GC progression and provide new candidate targets against this disease.
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http://dx.doi.org/10.1186/s13046-021-01848-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7851912PMC
February 2021

CD63 negatively regulates hepatocellular carcinoma development through suppression of inflammatory cytokine-induced STAT3 activation.

J Cell Mol Med 2021 01 4;25(2):1024-1034. Epub 2020 Dec 4.

Department of Oncology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.

Tetraspanin CD63 has been widely implicated in tumour progression of human malignancies. However, its role in the tumorigenesis and metastasis of hepatocellular carcinoma (HCC) remains unclear yet. In the present study, we aimed to investigate the specific function and underlying mechanisms of CD63 in HCC progression. CD63 expression in HCC tissues was detected using immunohistochemistry and quantitative real-time PCR analyses; effects of CD63 on HCC cell proliferation and migration were investigated by CCK-8 assay, colony formation assay, transwell assay and a xenograft model of nude mice. RNA-sequencing, bioinformatics analysis, dual-luciferase reporter assay and Western blot analysis were performed to explore the underlying molecular mechanisms. Results of our experiments showed that CD63 expression was frequently reduced in HCC tissues compared with adjacent normal tissues, and decreased CD63 expression was significantly associated with larger tumour size, distant site metastasis and higher tumour stages of HCC. Overexpression of CD63 inhibited HCC cell proliferation and migration, whereas knockdown of CD63 promoted these phenotypes. IL-6, IL-27 and STAT3 activity was regulated by CD63, and blockade of STAT3 activation impaired the promotive effects of CD63 knockdown on HCC cell growth and migration. Our findings identified a novel CD63-IL-6/IL-27-STAT3 axis in the development of HCC and provided a potential target for the diagnosis and treatment of this disease.
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http://dx.doi.org/10.1111/jcmm.16167DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7812266PMC
January 2021

Topology-Controlled Photonic Cavity Based on the Near-Conservation of the Valley Degree of Freedom.

Phys Rev Lett 2020 Nov;125(21):213902

School of Applied and Engineering Physics, Cornell University, Ithaca, New York 14853, USA.

We demonstrate a novel path to localizing topologically nontrivial photonic edge modes along their propagation direction. Our approach is based on the near-conservation of the photonic valley degree of freedom associated with valley-polarized edge states. When the edge state is reflected from a judiciously oriented mirror, its optical energy is localized at the mirror surface because of an extended time delay required for valley index flipping. The degree of energy localization at the resulting topology-controlled photonic cavity is determined by the valley-flipping time, which is in turn controlled by the geometry of the mirror. Intuitive analytic descriptions of the "leaky" and closed topology-controlled photonic cavities are presented, and two specific designs-one for the microwave and the other for the optical spectral ranges-are proposed.
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http://dx.doi.org/10.1103/PhysRevLett.125.213902DOI Listing
November 2020

Mydgf promotes Cardiomyocyte proliferation and Neonatal Heart regeneration.

Theranostics 2020 11;10(20):9100-9112. Epub 2020 Jul 11.

State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China.

Myeloid-derived growth factor (Mydgf), a paracrine protein secreted by bone marrow-derived monocytes and macrophages, was found to protect against cardiac injury following myocardial infarction (MI) in adult mice. We speculated that Mydgf might improve heart function myocardial regeneration, which is essential for discovering the target to reverse heart failure. Two genetic mouse lines were used: global Mydgf knockout () and mice. Two models of cardiac injury, apical resection was performed in neonatal and MI was performed in adult mice. Quantitative reverse transcription-polymerase chain reaction, western blot and flow cytometry were performed to study the protein expression. Immunofluorescence was performed to detect the proliferation of cardiomyocytes. Heart regeneration and cardiac function were evaluated by Masson's staining and echocardiography, respectively. RNA sequencing was employed to identify the key involved in Mydgf-induced cardiomyocyte proliferation. Mydgf recombinant protein injection was performed as a therapy for cardiac repair post MI in adult mice. Mydgf expression could be significantly induced in neonatal mouse hearts after cardiac injury. Unexpectedly, we found that Mydgf was predominantly expressed by endothelial cells rather than macrophages in injured neonatal hearts. Mydgf deficiency impeded neonatal heart regeneration and injury-induced cardiomyocyte proliferation. Mydgf recombinant protein promoted primary mouse cardiomyocyte proliferation. Employing RNA sequencing and functional verification, we demonstrated that c-Myc/FoxM1 pathway mediated Mydgf-induced cardiomyocyte expansion. Mydgf recombinant protein improved cardiac function in adult mice after MI injury with inducing cardiomyocyte proliferation. Mydgf promotes cardiomyocyte proliferation by activating c-Myc/FoxM1 pathway and improves heart regeneration both in neonatal and adult mice after cardiac injury, providing a potential target to reverse cardiac remodeling and heart failure.
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http://dx.doi.org/10.7150/thno.44281DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7415811PMC
June 2021

Vicenin-2 Treatment Attenuated the Diethylnitrosamine-Induced Liver Carcinoma and Oxidative Stress through Increased Apoptotic Protein Expression in Experimental Rats.

J Environ Pathol Toxicol Oncol 2020 ;39(2):113-123

Beihua University, Jilin, China.

Liver cancer or hepatocellular carcinoma is considered to be the third leading cause of death among all other cancers. The rate of liver cancer occurrence is high, and the rate of recovery is low. In this study, we investigated the therapeutic efficacy of vicenin-2 against the diethylnitrosamine-induced liver carcinoma in experimental rats. Diethylnitrosamine was widely employed as a carcinogenic agent to stimulate the cancer in animal models. Our results indicated that vicenin-2 administration effectively attenuates the diethylnitrosamine-induced physiological and pharmacological alterations in the experimental rats. Vicenin-2 treatment significantly enhanced the pathological lesions and decreased the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and α-fetoprotein (AFP) in serum. We also observed that vicenin-2 reduced the production of reactive oxygen species, decreased the liver weight, upregulated expression of apoptotic proteins, and decreased the histological changes in the liver, which are induced by the diethylnitrosamine in rats. Moreover, vicenin-2 downregulates antiapoptotic Bcl-2 and Bcl-xL, and upregulates the proapoptotic Bax and caspase. Hence, our results suggested that vicenin-2 had a highly therapeutic effect in reversing diethylnitrosamine-induced liver carcinoma in rats, which might be related to the apoptosis induced by vicenin-2. Therefore vicenin-2 could be a good candidate for future therapeutic use to inhibit chemically induced liver cancer.
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http://dx.doi.org/10.1615/JEnvironPatholToxicolOncol.2020031892DOI Listing
August 2020

Camrelizumab in advanced or metastatic solid tumour patients with DNA mismatch repair deficient or microsatellite instability high: an open-label prospective pivotal trial.

J Cancer Res Clin Oncol 2020 Oct 4;146(10):2651-2657. Epub 2020 Jul 4.

Shanghai East Hospital, Tongji University School of Medicine, No. 150 Ji-Mo Rd., Shanghai, 200120, China.

Purpose: Patients with DNA mismatch repair-deficient (dMMR)/microsatellite instability-high (MSI-H) cancers are prone to response to programmed cell death-1 (PD-1) checkpoint inhibitors. Therefore, we explored the efficacy and safety of a PD-1 checkpoint inhibitor camrelizumab in advanced or metastatic solid tumour with dMMR/MSI-H.

Methods: Patients with dMMR/MSI-H advanced or metastatic solid tumours who had received at least one line of prior systemic chemotherapy were recruited. Camrelizumab was given intravenously 200 mg every 2-week treatment cycle. The primary endpoint was objective response rate according to Response Evaluation Criteria in Solid Tumours v1.1.

Results: Twelve patients were enrolled. As data cutoff, eight patients (66.7%, 95% CI 34.9-90.1) achieved objective response. Disease control rate reached 100% (95% CI 73.5-100). Progression-free survival rate at 12 months was 83.3% (95% CI 48.2-95.6), and overall survival rate at 12 months was 90% (95% CI 47.3-98.5). The most common treatment-related adverse events were reactive cutaneous capillary endothelial proliferation (100%), increased alanine aminotransferase (41.7%), and increased aspartate aminotransferase (41.7%).

Conclusions: Camrelizumab provided durable objective response and disease control in pre-treated patients with dMMR/MSI-H advanced or metastatic solid tumour, being a promising treatment option for these patients.
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http://dx.doi.org/10.1007/s00432-020-03251-5DOI Listing
October 2020

gp130 Controls Cardiomyocyte Proliferation and Heart Regeneration.

Circulation 2020 09 30;142(10):967-982. Epub 2020 Jun 30.

State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (Yandong Li, J.F., S.S., H. Li, H. Lian, L.L., S.H., Y.N.).

Background: A key cause of the high mortality of cardiovascular diseases is the cardiomyocyte inability to renew after cardiac injury. As a promising strategy to supplement functional myocytes for cardiac repair, there is a pressing need to understand the cellular and molecular mechanisms of heart regeneration.

Methods: Seven genetic mouse lines were used: global OSM (oncostatin M) knockout, monocyte-/macrophage-specific OSM deletion, cardiomyocyte-specific lines, including OSM receptor deletion, gp130 (glycoprotein 130) deletion, gp130 activation, and Yap (yes-associated protein) ablation with gp130 activation mice. A series of molecular signaling experiments, including RNA sequencing, immunostaining, coimmunoprecipitation, and imaging flow cytometry, were conducted. Two models of cardiac injury, apical resection and myocardial infarction operation, were performed in neonatal, juvenile, and adult mice. Heart regeneration and cardiac function were evaluated by Masson staining and echocardiography, respectively. Gene recombinant adenovirus-associated virus was constructed and infected myocardial-infarcted mice as a gene therapy.

Results: OSM was identified by RNA sequencing as a key upstream regulator of cardiomyocyte proliferation during neonatal heart regeneration in mice. Cardiomyocyte proliferation and heart regeneration were suspended in neonatal mice after cardiac injury when OSM was conditionally knockout in macrophages. The cardiomyocyte-specific deficiency of the OSM receptor heterodimers, OSM receptor and gp130, individually in cardiomyocytes reduced myocyte proliferation and neonatal heart regeneration. Conditional activation of gp130 in cardiomyocytes promoted cardiomyocyte proliferation and heart regeneration in juvenile and adult mice. Using RNA sequencing and functional screening, we found that Src mediated gp130-triggered cardiomyocyte proliferation by activating Yap (yes-associated protein) with Y357 phosphorylation independently of the Hippo pathway. Cardiomyocyte-specific deletion of Yap in mice blocked the effect of gp130 activation-induced heart regeneration in juvenile mice. Gene therapy with adenovirus-associated virus encoding constitutively activated gp130 promoted cardiomyocyte proliferation and heart regeneration in adult mice after myocardial infarction.

Conclusions: Macrophage recruitment is essential for heart regeneration through the secretion of OSM, which promotes cardiomyocyte proliferation. As the coreceptor of OSM, gp130 activation is sufficient to promote cardiomyocyte proliferation by activating Yap through Src during heart regeneration. gp130 is a potential therapeutic target to improve heart regeneration after cardiac injury.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.119.044484DOI Listing
September 2020

The enhanced treatment efficacy of invasive brain glioma by dual-targeted artemether plus paclitaxel micelles.

Artif Cells Nanomed Biotechnol 2020 Dec;48(1):983-996

Shanxi Key Laboratory of Innovative Drug for the Treatment of Serious Diseases Basing on the Chronic Inflammation, Shanxi University of Chinese Medicine, Jinzhong, China.

High grade-gliomas are highly invasive and prone to metastasis, leading to poor survival and prognosis. Currently, we urgently need a new treatment strategy to effectively inhibit glioma. In this study, artemether and paclitaxel were used as two agents for tumour suppression. Two functional materials were synthesised and modified on the surface of the micelle as targeting molecules. The addition of two functional materials confers the ability of the micelles to effectively cross the blood-brain barrier (BBB) and then target the glioma cells. Thus, this dual-targeted delivery system allows the drug to play a better role in inhibiting tumour invasion and vasculogenic mimicry (VM) channels. In this paper, the anticancer effects of dual-targeted artemether plus paclitaxel micelles on glioma U87 cells were studied in three aspects: (I) and targeting assessment, including the role of penetrating BBB and targeting glioma; (II) regulation of invasion-associated proteins; (III) Inhibition of VM channels formation and invasion ; (IV) The study of pharmacodynamics in tumour-bearing mice. These results suggest that dual-targeted artemether plus paclitaxel micelle may provide a new strategy to treat glioma inhibiting invasive and VM channels.
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http://dx.doi.org/10.1080/21691401.2020.1773489DOI Listing
December 2020
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