Publications by authors named "Danyang Chen"

106 Publications

Exploring synthetic lethal network for the precision treatment of clear cell renal cell carcinoma.

Sci Rep 2022 Aug 2;12(1):13222. Epub 2022 Aug 2.

Department of Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China.

The emerging targeted therapies have revolutionized the treatment of advanced clear cell renal cell carcinoma (ccRCC) over the past 15 years. Nevertheless, lack of personalized treatment limits the development of effective clinical guidelines and improvement of patient prognosis. In this study, large-scale genomic profiles from ccRCC cohorts were explored for integrative analysis. A credible method was developed to identify synthetic lethality (SL) pairs and a list of 72 candidate pairs was determined, which might be utilized to selectively eliminate tumors with genetic aberrations using SL partners of specific mutations. Further analysis identified BRD4 and PRKDC as novel medical targets for patients with BAP1 mutations. After mapping these target genes to the comprehensive drug datasets, two agents (BI-2536 and PI-103) were found to have considerable therapeutic potentials in the BAP1 mutant tumors. Overall, our findings provided insight into the overview of ccRCC mutation patterns and offered novel opportunities for improving individualized cancer treatment.
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http://dx.doi.org/10.1038/s41598-022-16657-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9345903PMC
August 2022

Inhibition of H1N1 Influenza Virus-induced Apoptosis by Ebselen Through ROS-mediated ATM/ATR Signaling Pathways.

Biol Trace Elem Res 2022 Jul 27. Epub 2022 Jul 27.

Center Laboratory, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Yuexiu District, No 318 Renminzhong Road, Guangzhou, 510120, China.

Influenza A viruses can cause global outbreaks and seasonal pandemics. However, the use of conventional anti-influenza drugs leads to an increase in drug-resistant mutations in influenza viruses worldwide. Therefore, numerous studies have focused on developing effective anti-influenza drugs. It is feasible to treat influenza by targeting influenza-mediated oxidative damage. Ebselen is a synthetic organoselenium compound which provides glutathione peroxidase-like activity. It has been shown to play a role in anti-influenza therapy, but the mechanism remains to be further explored. This experiment verified the anti-influenza effect of ebselen. CCK-8 and PCR showed that ebselen had a significant inhibitory effect on virus replication compared with the virus group. In addition, the mechanistic investigations revealed that ebselen could inhibit influenza-mediated apoptosis, mitochondrial damage, accumulation of reactive oxygen species, and DNA breakage. At the same time, ebselen significantly inhibited the phosphorylation of ATM and ATR and promoted the activation of PARP and Caspase-3. Ebselen, on the other hand, reduced the inflammatory response caused by influenza. These results suggest that ebselen is a promising inhibitor for H1N1.
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http://dx.doi.org/10.1007/s12011-022-03369-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9330958PMC
July 2022

Self-healing hydrogel based on polyphosphate-conjugated pectin with hemostatic property for wound healing applications.

Biomater Adv 2022 Aug 6;139:212974. Epub 2022 Jun 6.

College of Chemistry and Environmental Science, Hebei University, Baoding City 071002, China; Key Laboratory of Pathogenesis mechanism and control of inflammatory-autoimmune diseases in Hebei Province, Hebei University, Baoding City 071002, China. Electronic address:

Self-healing hydrogels have important application in hemostasis and wound repairing. In this research, pectin based self-healing hydrogel was fabricated with conjugated polyphosphate for hemostatic and wound healing applications. The hydrogel formed without any stimulus and hydrogel kept its biocompatibility; at the same time, the hydrogel degraded completely by enzyme and in vivo. The polyphosphate conjugated hydrogel also showed self-healing property and sustained release performance with strong coagulation characteristic. More importantly, the in vivo experiment revealed that the polyphosphate conjugated hydrogel reduced the blood loss and hemostasis time in hemorrhage model; meanwhile, the hydrogel accelerated the wound repairing rate of the open wound by preventing bacterial invasion. Altogether, the PolyP conjugated hemostatic pectin-based hydrogel is a good candidate as wound dressing material applied in clinic or open wound repairing.
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http://dx.doi.org/10.1016/j.bioadv.2022.212974DOI Listing
August 2022

Smoke-induced SAV1 Gene Promoter Hypermethylation Disrupts YAP Negative Feedback and Promotes Malignant Progression of Non-small Cell Lung Cancer.

Int J Biol Sci 2022 11;18(11):4497-4512. Epub 2022 Jul 11.

Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou Key Laboratory of "Translational Medicine on Malignant Tumor Treatment", Guangzhou city, Guangdong, P. R. China.

YAP (gene symbol ) as a potential oncoprotein, is positively correlated with the malignancy of various tumors. However, overexpression of YAP alone in multiple normal tissue cells has failed to induce tumor formation and the underlying mechanism is poorly understood. Herein, we show that YAP activation directly induces transcription of its negative regulator, SAV1, to constitute a negative feedback loop, which plays a vital role in maintaining lung epithelial cell homeostasis and was dysregulated in non-small cell lung cancer (NSCLC). Notably, smoking promotes the hypermethylation of the promoter region, which disrupts YAP negative feedback by inactivating the Hippo pathway. Besides, exogenous overexpression of SAV1 can act as a traffic protein, activating the Hippo signaling and concurrently inhibiting the WNT pathway to decrease cancer cell growth. Furthermore, using the lung cancer organoids, we found that lentivirus-mediated SAV1 gene transfer combined with methylation inhibitor and YAP-TEAD inhibitor is a potential feasible clinical medication regimen for the lung cancer patient, especially among the smoking population. Thus, this SAV1 mediated feedback loop provides an efficient mechanism to establish the robustness and homeostasis of YAP regulation and as a potential target of gene therapy for the smoking NSCLC population.
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http://dx.doi.org/10.7150/ijbs.73428DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9295071PMC
July 2022

Epigallocatechin-3-gallate induced HepG2 cells apoptosis through ROS-Mediated AKT /JNK and p53 signaling pathway..

Curr Cancer Drug Targets 2022 Jul 5. Epub 2022 Jul 5.

Center Laboratory, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.

Background: Hepatocarcinoma is the third leading cause of cancer-related deaths around the world. Recently, some studies have reported that Epigallocatechin-3-gallate (EGCG) may have the potential for anti-cancer. However, the affection and putative mechanisms of cytotoxicity induced by EGCG in HepG2 cells remain unknown. Based on the above, the present study evaluated the effect of EGCG on the cytotoxic and anti-cancer mechanisms on HepG2 cells. Methods The effect of EGCG on the apoptosis of Hep-G2 cells and its mechanism were studied by cell counting kit-8, mitochondrial membrane potential assay with JC-1, Annexin V-FITC apoptosis detection, cell cycle, and apoptosis analysis, one step TUNEL apoptosis assay, caspase 3 activity assay, caspase 9 activity Assay, Reactive Oxygen Species assay, and Western blot. Results EGCG-induced HepG2 cell apoptosis was confirmed by accumulation of the sub-G1 cells population, translocation of phosphatidylserine, depletion of mitochondrial membrane potential, DNA fragmentation, caspase-3 activation, caspase-9 activation, and poly (ADP-ribose) polymerase cleavage. Furthermore, EGCG enhanced cytotoxic effects on HepG2 cells and triggered intracellular reactive oxygen species; the signaling pathways of AKT, JNK, and p53 were activated to advance cell apoptosis.

Conclusion: The results reveal that EGCG may provide useful information on EGCG-induced HepG2 cell apoptosis and be an appropriate candidate for cancer chemotherapy.
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http://dx.doi.org/10.2174/1568009622666220705101642DOI Listing
July 2022

L-Selenocysteine induced HepG-2 cells apoptosis through reactive oxygen species-mediated signaling pathway.

Mol Biol Rep 2022 Jun 18. Epub 2022 Jun 18.

Center Laboratory, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, 510120, Guangzhou, China.

Background: Currently, Liver cancer is the fifth most common tumor and the second most important reason for cancer-related death in the world. However, there are still many limitations of the clinical treatment of liver cancer, and new treatment options are clearly needed. Fortunately, studies have shown that L-Selenocysteine has a certain effect on cancer. This study was to investigate the effects of L-Selenocysteine on the inhibition of cell proliferation and the promotion of apoptosis of HepG-2 cells through ROS mediated fine signaling pathway.

Materials And Methods: CCK-8 assay was applied to evaluating the cytotoxic effect of L-Selenocysteine on HepG-2 cells. Electron microscopy, flow cytometry and Western Blot was utilization in further researching cells signaling pathways.

Results: The growth of HepG-2 cells was inhibited by L-selenocysteine ​​treatment in a dose-dependent manner. The cell viability decreased to 52.20%, 43.20% and 30.83% under the treatment of 4, 8, 16 µM L-selenocysteine, respectively. L-Selenocysteine had higher cytotoxicity towards HepG-2 cells than normal cells. L-Selenocysteine can induce the apoptosis of HepG-2 cells by increasing the DNA fragmentation, and activating the Caspase-3. In addition, it was found that the mechanism of the induction to HepG-2 cell apoptosis by L-Selenocysteine was closely related to the overproduction of ROS and promoted apoptosis through the Bcl-2 signaling pathway.

Conclusions: Our data suggest that L-selenocysteine ​​may cause mitochondrial damage and subsequently stimulate ROS production. ROS can damage cellular DNA and mediate the production of Casapase-8, Bid, Bcl-2 and other proteins, affecting downstream signaling pathways, and ultimately induced apoptosis.
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http://dx.doi.org/10.1007/s11033-022-07655-zDOI Listing
June 2022

Tumor-associated macrophages promote epithelial-mesenchymal transition and the cancer stem cell properties in triple-negative breast cancer through CCL2/AKT/β-catenin signaling.

Cell Commun Signal 2022 06 17;20(1):92. Epub 2022 Jun 17.

Guangzhou Key Laboratory of "Translational Medicine on Malignant Tumor Treatment", Affiliated Cancer Hospital & Institute of Guangzhou Medical University, No.78 Hengzhigang Road, Guangzhou, 510095, Guangdong, China.

Background: Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer with poor prognosis and limited treatment. As a major component of the tumor microenvironment, tumor-associated macrophages (TAMs) play an important role in facilitating the aggressive behavior of TNBC. This study aimed to explore the novel mechanism of TAMs in the regulation of epithelial-mesenchymal transition (EMT) and cancer stem cell (CSC) properties in TNBC.

Methods: Expression of the M2-like macrophage marker CD163 was evaluated by immunohistochemistry in human breast cancer tissues. The phenotype of M2 macrophages polarized from Tohoku-Hospital-Pediatrics-1 (THP1) cells was verified by flow cytometry. Transwell assays, wound healing assays, western blotting, flow cytometry, ELISA, quantitative polymerase chain reaction (qPCR), luciferase reporter gene assays, and immunofluorescence assays were conducted to investigate the mechanism by which TAMs regulate EMT and CSC properties in BT549 and HCC1937 cells.

Results: Clinically, we observed a high infiltration of M2-like tumor-associated macrophages in TNBC tissues and confirmed that TAMs were associated with unfavorable prognosis in TNBC patients. Moreover, we found that conditioned medium from M2 macrophages (M2-CM) markedly promoted EMT and CSC properties in BT549 and HCC1937 cells. Mechanistically, we demonstrated that chemokine (C-C motif) ligand 2 (CCL2) secretion by TAMs activated Akt signaling, which in turn increased the expression and nuclear localization of β-catenin. Furthermore, β-catenin knockdown reversed TAM-induced EMT and CSC properties.

Conclusions: This study provides a novel mechanism by which TAMs promote EMT and enhance CSC properties in TNBC via activation of CCL2/AKT/β-catenin signaling, which may offer new strategies for the diagnosis and treatment of TNBC. Video Abstract.
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http://dx.doi.org/10.1186/s12964-022-00888-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9205034PMC
June 2022

Efficient capture of circulating tumor cells with low molecular weight folate receptor-specific ligands.

Sci Rep 2022 05 20;12(1):8555. Epub 2022 May 20.

Department of Chemistry, Purdue Center for Cancer Research, Purdue Institute for Drug Discovery, Purdue University, 720 Clinic Drive, West Lafayette, IN, 47907, USA.

Retrieval of circulating tumor cells (CTC) has proven valuable for assessing a patient's cancer burden, evaluating response to therapy, and analyzing which drug might treat a cancer best. Although most isolation methods retrieve CTCs based on size, shape, or capture by tumor-specific antibodies, we explore here the use of small molecule tumor-specific ligands linked to magnetic beads for CTC capture. We have designed folic acid-biotin conjugates with different linkers for the capture of folate receptor (FR) + tumor cells spiked into whole blood, and application of the same technology to isolate FR + CTCs from the peripheral blood of both tumor-bearing mice and non-small cell lung patients. We demonstrate that folic acid linked via a rigid linker to a flexible PEG spacer that is in turn tethered to a magnetic bead enables optimal CTC retrieval, reaching nearly 100% capture when 100 cancer cells are spiked into 1 mL of aqueous buffer and ~ 90% capture when the same quantity of cells is diluted into whole blood. In a live animal model, the same methodology is shown to efficiently retrieve CTCs from tumor-bearing mice, yielding cancer cell counts that are proportional to total tumor burden. More importantly, the same method is shown to collect ~ 29 CTCs/8 mL peripheral blood from patients with non-small cell lung cancer. Since the ligand-presentation strategy optimized here should also prove useful in targeting other nanoparticles to other cells, the methods described below should have general applicability in the design of nanoparticles for cell-specific targeting.
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http://dx.doi.org/10.1038/s41598-022-12118-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9122947PMC
May 2022

Assessment of the Novel, Practical, and Prognosis-Relevant TNM Staging System for Stage I-III Cutaneous Melanoma.

Front Oncol 2022 29;12:738298. Epub 2022 Apr 29.

Department of Plastic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China.

Background: The clinical TNM staging system does not differ between the 7 and 8 editions of the American Joint Committee on Cancer (AJCC) staging manual. A more practical TNM staging system for patients with stage I-III cutaneous melanoma are needed.

Methods: Data were accessed from the Surveillance, Epidemiology, and End Results (SEER) open database. We divided the patients into 32 groups based on the T and N categories. The Kaplan-Meier survival curves and treatment guidelines were used to proposed a new TNM staging system. Cox proportional hazards model and 1000-person-years were used to verify accuracy.

Results: This retrospective study included 68 861 patients from 2010 to 2015. The new proposed staging system was as follows: stage IA, T1aN0M0; stage IB, T1b/T2aN0M0; stage IIA, T3-4aN0M0 and T2bN0M0; stage IIB, T1-4aN1-2M0 and T3-4bN0M0; and stage III, T1-4aN3M0 and T1-4bN1-3M0. Hazard ratios for the new stages IB, IIA, IIB, and III, with stage IA as reference, were 4.311 (95% confidence interval [CI]: 3.217-5.778), 8.993 (95% CI: 6.637-12.186), 13.179 (95% CI: 9.435-18.407), and 20.693 (95% CI: 13.655-31.356), respectively (all p-values < 0.001). Cancer-specific mortality rates per 1000-person-years were 0.812 (95% CI: 0.674-0.978), 6.612 (95% CI: 5.936-7.364), 22.228 (95% CI: 20.128-24.547), 50.863 (95% CI: 47.472-54.496) and 120.318 (95% CI: 112.596-128.570) for stages IA, IB, IIA, IIB and III, respectively.

Conclusion: We developed a more practical and prognosis-relevant staging system than that of the 8 edition AJCC manual for patients with stage I-III cutaneous melanoma. Treatments using this new model would improve the quality of life and survival rates of patients with melanoma.
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http://dx.doi.org/10.3389/fonc.2022.738298DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9104117PMC
April 2022

Mesh-like electrospun membrane loaded with atorvastatin facilitates cutaneous wound healing by promoting the paracrine function of mesenchymal stem cells.

Stem Cell Res Ther 2022 05 7;13(1):190. Epub 2022 May 7.

Department of Plastic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China.

Background: Functional electrospun membranes are promising dressings for promoting wound healing. However, their microstructure and drug loading capacity need further improvements. It is the first time to design a novel mesh-like electrospun fiber loaded with atorvastatin (ATV) and investigated its effects on paracrine secretion by bone marrow-derived mesenchymal stem cells (BMSCs) and wound healing in vivo.

Methods: We fabricated a mesh-like electrospun membrane using a copper mesh receiver. The physical properties of the membranes were evaluated by SEM, FTIR spectroscopy, tensile strength analysis, and contrast angle test. Drug release was measured by plotting concentration as a function of time. We tested the effects of conditioned media (CM) derived from BMSCs on endothelial cell migration and angiogenesis. We used these BMSCs and performed RT-PCR and ELISA to evaluate the expressions of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (b-FGF) genes and proteins, respectively. The involvement of FAK and AKT mechanotransduction pathways in the regulation of BMSC secretion by material surface topography was also investigated. Furthermore, we established a rat model of wound healing, applied ATV-loaded mesh-like membranes (PCL/MAT) seeded with BMSCs on wounds, and assessed their efficacy for promoting wound healing.

Results: FTIR spectroscopy revealed successful ATV loading in PCL/MAT. Compared with random electrospun fibers (PCL/R) and mesh-like electrospun fibers without drug load (PCL/M), PCL/MAT induced maximum promotion of human umbilical vein endothelial cell (HUVEC) migration. In the PCL/MAT group, the cell sheet scratches were nearly closed after 24 h. However, the cell sheet scratches remained open in other treatments at the same time point. The PCL/MAT promoted angiogenesis and led to the generation of longer tubes than the other treatments. Finally, the PCL/MAT induced maximum gene expression and protein secretion of VEGF and b-FGF. As for material surface topography effect on BMSCs, FAK and AKT signaling pathways were shown to participate in the modulation of MSC morphology and its paracrine function. In vivo, PCL/MAT seeded with BMSCs significantly accelerated healing and improved neovascularization and collagen reconstruction in the wound area compared to the other treatments.

Conclusions: The mesh-like topography of fibrous scaffolds combined with ATV release creates a unique microenvironment that promotes paracrine secretion of BMSCs, thereby accelerating wound healing. Hence, drug-loaded mesh-like electrospun membranes may be highly efficacious for wound healing and as artificial skin. It is a promising approach to solve the traumatic skin defect and accelerate recovery, which is essential to developing functional materials for future regenerative medicine.
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http://dx.doi.org/10.1186/s13287-022-02865-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9080129PMC
May 2022

Adaptive feedback threshold based demodulation for mobile visible light communication and positioning integrated system.

Opt Express 2022 Apr;30(8):13331-13344

In this paper, a novel adaptive feedback threshold (AFT) based demodulation for mobile visible light communication and positioning (VLCP) integrated system is proposed. The AFT can vary with the received signal without excessive fluctuation and support communication and positioning in mobile environment. For the VLCP integrated system with single light emitting diodes (LED) and multiple photodetectors (PDs), maximal ratio combining (MRC) and received optical power ratio (ROPR) based on the AFT is further achieved for communication and positioning with high performance, respectively. It is demonstrated that high credible communication and high accuracy positioning for the mobile integrated VLCP system can be realized by using the proposed AFT based demodulation. As a result, the implemented VLCP system with a moving speed of 1 m/s is evaluated experimentally. Average positioning error of 3.43 cm with 800 mA current and the bit error ratio (BER) with different currents are also obtained.
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http://dx.doi.org/10.1364/OE.456076DOI Listing
April 2022

TCRP1 activated by mutant p53 promotes NSCLC proliferation via inhibiting FOXO3a.

Oncogenesis 2022 Apr 22;11(1):19. Epub 2022 Apr 22.

Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou Key Laboratory of "Translational Medicine on Malignant Tumor Treatment", Hengzhigang Road 78#, Guangzhou, 510095, Guangdong, China.

Previously, our lab explored that tongue cancer resistance-associated protein (TCRP1) plays a central role in cancer chemo-resistance and progression. Absolutely, TCRP1 was significantly increased in lung cancer. But the mechanism is far from elucidated. Here, we found that TCRP1 was increased in p53-mutant non-small-cell lung cancer (NSCLC), comparing to that in NSCLC with wild type p53. Further study showed that mutant p53 couldn't bind to the promoter of TCRP1 to inhibit its expression. While the wild type p53 did so. Next, loss-and gain-of-function assays demonstrated that TCRP1 promoted cell proliferation and tumor growth in NSCLC. Regarding the mechanism, TCRP1 encouraged AKT phosphorylation and blocked FOXO3a nuclear localization through favoring FOXO3a ubiquitination in cytoplasm, thus, promoted cell cycle progression. Conclusionly, TCRP1 was upregulated in NSCLC cells with mutant p53. TCRP1 promoted NSCLC progression via regulating cell cycle.
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http://dx.doi.org/10.1038/s41389-022-00392-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9033812PMC
April 2022

Selenium nanoparticles inhibited H1N1 influenza virus-induced apoptosis by ROS-mediated signaling pathways.

RSC Adv 2022 Jan 31;12(7):3862-3870. Epub 2022 Jan 31.

Center Laboratory, Guangzhou Women and Children's Medical Center, Guangzhou Medical University No. 318 Renminzhong Road, Yuexiu District Guangzhou 510120 People's Republic of China

Influenza A (H1N1) viruses are distributed around the world and pose a threat to public health. Vaccination is the main treatment strategy to prevent influenza infection, but antiviral drugs also play an important role in controlling seasonal and pandemic influenza. Currently, as influenza viruses may be developing antiviral resistance, new agents with different modes of action are being investigated. Recently, selenium nanoparticles (SeNPs), which have antiviral effects, have attracted increasing attention in biomedical interventions. The appearance of nanotechnology has attracted great attention in the field of nanomedicine. SeNPs constitute an attractive vector platform for delivering a variety of drugs to action targets. SeNPs are being explored for potential therapeutic efficacy in a variety of oxidative stress and inflammation-mediated diseases, such as cancer, arthritis, diabetes, and kidney disease. SeNPs could inhibit infection of Madin-Darby canine kidney (MDCK) cells with H1N1 and prevent chromatin condensation and DNA fragmentation. ROS play a key role in physiological processes for apoptosis. SeNPs significantly inhibited the production of reactive oxygen species (ROS) in MDCK cells. Mechanistic investigation revealed that SeNPs inhibited the apoptosis induced by H1N1 virus infection in MDCK cells by improving the level of GPx1. Our results suggest that SeNPs are an effective selenium source and a promising H1N1 influenza antiviral candidate.
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http://dx.doi.org/10.1039/d1ra08658hDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8981154PMC
January 2022

Duvira Antarctic polysaccharide inhibited H1N1 influenza virus-induced apoptosis through ROS mediated ERK and STAT-3 signaling pathway.

Mol Biol Rep 2022 Jul 12;49(7):6225-6233. Epub 2022 Apr 12.

Center Laboratory, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510120, China.

Background: The H1N1 influenza virus causes acute respiratory tract infection, and its clinical symptoms are very similar to those of ordinary influenza. The disease develops rapidly. If the flu is not treated, complications such as pneumonia, respiratory failure, and multiple organ damage can occur, resulting in a high fatality rate. Influenza virus mutates rapidly. At present, there is no specific drug for H1N1, so it is an urgent need for clinical care to find new drugs to treat H1N1.

Materials And Methods: The polysaccharide derived from Durvillaea Antarctica green algae has a certain antiviral effect. In this study, the results of CCK-8, apoptosis cycle detection, JC-1 and Western blotting proved that Duvira Antarctic polysaccharide (DAPP) has the ability to inhibit H1N1 infection.

Results: CCK-8 test showed that the DAPP with concentration at 32 μg/mL had no toxicity to MDCK cells. In addition, DAPP reduced cell apoptosis by inhibiting the ERK signaling pathway. Meanwhile, DAPP could increase the expression of STAT3 and significantly inhibited proinflammatory cytokines.

Conclusions: In summary, these results suggested that DAPP may be potential with the ability to resist the H1N1 influenza virus.
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http://dx.doi.org/10.1007/s11033-022-07418-wDOI Listing
July 2022

Targeting nicotinamide N-methyltransferase overcomes resistance to EGFR-TKI in non-small cell lung cancer cells.

Cell Death Discov 2022 Apr 6;8(1):170. Epub 2022 Apr 6.

Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Key Laboratory of "Translational Medicine on Malignant Tumor Treatment,", Guangzhou, Guangdong, China.

Activating mutations of epidermal growth factor receptor (EGFR) contributes to the progression of non-small cell lung cancer (NSCLC). EGFR tyrosine kinase inhibitor (TKI)-targeted therapy has become the standard treatment for NSCLC patients with EGFR-mutations. However, acquired resistance to these agents remains a major obstacle for managing NSCLC. Here, we investigated a novel strategy to overcome EGFR TKI resistance by targeting the nicotinamide N-methyltransferase (NNMT). Using iTRAQ-based quantitative proteomics analysis, we identified that NNMT was significantly increased in EGFR-TKI-resistant NSCLC cells. Moreover, we found that NNMT expression was increased in EGFR-TKI-resistant NSCLC tissue samples, and higher levels were correlated with shorter progression-free survival in EGFR-TKI-treated NSCLC patients. Knockdown of NNMT rendered EGFR-TKI-resistant cells more sensitive to EGFR-TKI, whereas overexpression of NNMT in EGFR-TKI-sensitive cells resulted in EGFR-TKI resistance. Mechanically, upregulation of NNMT increased c-myc expression via SIRT1-mediated c-myc deacetylation, which in turn promoted glycolysis and EGFR-TKI resistance. Furthermore, we demonstrated that the combination of NNMT inhibitor and EGFR-TKI strikingly suppressed the growth of EGFR-TKI-resistant NSCLC cells both in vitro and in vivo. In conclusion, our research indicated that NNMT overexpression is important for acquired resistance to EGFR-TKI and that targeting NNMT might be a potential therapeutic strategy to overcome resistance to EGFR TKI.
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http://dx.doi.org/10.1038/s41420-022-00966-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8986855PMC
April 2022

A nanoconcrete welding strategy for constructing high-performance wound dressing.

Bioact Mater 2022 Aug 18;14:31-41. Epub 2021 Dec 18.

Central Laboratory, Longgang District People's Hospital of Shenzhen & the Third Affiliated Hospital (Provisional) of the Chinese University of Hong Kong, Shenzhen, Guangdong, China.

Engineering biomaterials to meet specific biomedical applications raises high requirements of mechanical performances, and simultaneous strengthening and toughening of polymer are frequently necessary but very challenging in many cases. In this work, we propose a new concept of nanoconcrete welding polymer chains, where mesoporous CaCO (mCaCO) nanoconcretes which are composed of amorphous and nanocrystalline phases are developed to powerfully weld polymer chains through siphoning-induced occlusion, hydration-driven crystallization and dehydration-driven compression of nanoconcretes. The mCaCO nanoconcrete welding technology is verified to be able to remarkably augment strength, toughness and anti-fatigue performances of a model polymer poly(3-hydroxybutyrate--3-hydroxyvalerate)-based porous membrane. Mechanistically, we have revealed polymer-occluded nanocrystal structure and welding-derived microstress which is much stronger than interfacial Van der Waals force, thus efficiently preventing the generation of microcracks and repairing initial microcracks by microcracks-induced hydration, crystallization and polymer welding of mCaCO nanoconcretes. Constructed porous membrane is used as wound dressing, exhibiting a special nanoplates-constructed surface topography as well as a porous structure with plentiful oriented, aligned and opened pore channels, improved hydrophilicity, water vapor permeability, anti-bacterial and cell adherence, in support of wound healing and skin structural/functional repairing. The proposed nanoconcrete-welding-polymer strategy breaks a new pathway for improving the mechanical performances of polymers.
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http://dx.doi.org/10.1016/j.bioactmat.2021.12.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8892149PMC
August 2022

Poly(aspartic acid) based self-healing hydrogel with blood coagulation characteristic for rapid hemostasis and wound healing applications.

Colloids Surf B Biointerfaces 2022 Jun 1;214:112430. Epub 2022 Mar 1.

College of Chemistry and Environmental Science, Hebei University, Baoding, Hebei 071002, China; Key Laboratory of Pathogenesis mechanism and control of inflammatory-autoimmune diseases in Hebei Province, Hebei University, Baoding, Hebei 071002, China. Electronic address:

External hemorrhage, caused by insufficient hemostasis or surgical failure, could leads to shock or even tissue necrosis as the results of excessive blood loss. Furthermore, delayed coagulation, chronic inflammation, bacterial infection and slow cell proliferation are also major challenges to effective wound repairing. In this study, a novel hemostatic hydrogel was prepared by cross-linking inorganic polyphosphate (PolyP) conjugated poly(aspartic acid) hydrazide (PAHP) and PEO dialdehyde (PEO DA). Based on the dynamic characteristics of the acylhydrazone bond, the hydrogel could repair its cracks when broken under external forces. At the same time, the hydrogel showed outstanding biocompatibility and tissue adhesion with remarkable hemostatic performance. The New Zealand rabbit ear artery used as a in vivo hemostasis model and the results showed the PAHP hydrogel could stop bleeding of traumatic wound and reduce blood loss significantly. Meanwhile, the PAHP hydrogel presented intrinsic antibacterial activity, thus could inhibit the bacterial infection. In addition, the hydrogel loaded with mouse epidermal growth factor (mEGF) accelerated the wound repair rate and promoted the regeneration of fresh tissue in the mouse full thickness skin defect model. Altogether, the PAHP hydrogels exhibits great potential in the biomedical application, especially in wound dressing materials and tissue repairing.
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http://dx.doi.org/10.1016/j.colsurfb.2022.112430DOI Listing
June 2022

Investigation on the Correlation between Dispersion Characteristics at Terahertz Range and Dielectric Permittivity at Low Frequency of Epoxy Resin Nanocomposites.

Polymers (Basel) 2022 Feb 21;14(4). Epub 2022 Feb 21.

State Key Laboratory of Electrical Insulation and Power Equipment, Xi'an Jiaotong University, Xi'an 710049, China.

Despite the extensive research on nanocomposites, a fundamental theory on the interface region is still difficult to achieve. In the present paper, we chose epoxy resin and nano-SiO, nano-SiC, nano-ZnO to prepare three kinds of nanocomposites. The dispersion characteristics at the terahertz range and dielectric permittivity at 1 Hz of epoxy resin-based nanocomposites were investigated. The reduction of the permittivity of nanocomposites at a slight filler concentration was absent at the terahertz range. The measurement results at 1 Hz show that the interaction between nano-SiO, nano-SiC particles and epoxy resin was strong with the modification of the silane coupling agent. However, the modification of nano-ZnO particles was invalid. The Lorentz harmonic oscillator model was employed to fit the dispersion characteristics. The relevance between the damping constant and the dielectric permittivity at low frequency was established, indicating that the increase in the damping coefficient results from the restriction of the molecular chain motion by the interfacial region. The present results in this paper reveal a bright prospect of terahertz time-domain spectroscopy in establishing the theory of nanocomposite dielectric.
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http://dx.doi.org/10.3390/polym14040827DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8879792PMC
February 2022

Decidual macrophage derived MMP3 contributes to extracellular matrix breakdown in spiral artery remodeling in early human pregnancy.

J Reprod Immunol 2022 03 11;150:103494. Epub 2022 Feb 11.

Division of Uterine Vascular Biology, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China. Electronic address:

Remodeling of the uterine spiral arteries is required for a successful pregnancy. This process requires the co-ordinated activity of a number of different cell types including uterine natural killer cells, decidual macrophages, extravillous trophoblast cells, vascular smooth muscle cells and endothelial cells. We have previously demonstrated that decidual macrophages facilitate breakdown of fibronectin and laminin in a model of spiral artery remodeling. The aim of the current study was to determine which matrix metalloproteinases (MMPs) decidual macrophages express and play roles in extracellular matrix (ECM) breakdown in vascular remodeling. Decidual macrophages were isolated from first trimester decidua and cultured for 24 h to obtain conditioned medium. MMP secretion was assessed by a membrane based array and immunohistochemistry of decidual sections. In addition, the chorionic plate artery (CPA) model was used with decidual macrophage conditioned medium, with and without a MMP3 inhibitor and ECM protein expression assessed using quickscore. The decidual macrophages secreted a wide range of MMPs, with MMP3 being the most predominant. Co-localization of MMP3 to decidual macrophages was confirmed by immunohistochemistry. Decidual macrophage conditioned medium facilitated breakdown of laminin and fibronectin in the CPA model, an effect that was abrogated by the MMP3 inhibitor. These data further support the role of decidual macrophages in tissue remodeling in the first trimester of pregnancy. An alteration in their numbers or phenotype would impact spiral artery remodeling and contribute to the etiology of a number of complications of pregnancy.
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http://dx.doi.org/10.1016/j.jri.2022.103494DOI Listing
March 2022

Light-triggered nitric oxide release and structure transformation of peptide for enhanced intratumoral retention and sensitized photodynamic therapy.

Bioact Mater 2022 Jun 28;12:303-313. Epub 2021 Oct 28.

Marshall Laboratory of Biomedical Engineering, School of Biomedical Engineering, Health Science Center, Shenzhen University, No. 1066 Xueyuan Avenue, Shenzhen, 518060, Guangdong, China.

Tumor-targeted delivery of nanomedicine is of great importance to improve therapeutic efficacy of cancer and minimize systemic side effects. Unfortunately, nowadays the targeting efficiency of nanomedicine toward tumor is still quite limited and far from clinical requirements. In this work, we develop an innovative peptide-based nanoparticle to realize light-triggered nitric oxide (NO) release and structural transformation for enhanced intratumoral retention and simultaneously sensitizing photodynamic therapy (PDT). The designed nanoparticle is self-assembled from a chimeric peptide monomer, TPP-RRRKLVFFK-Ce6, which contains a photosensitive moiety (chlorin e6, Ce6), a β-sheet-forming peptide domain (Lys-Leu-Val-Phe-Phe, KLVFF), an oligoarginine domain (RRR) as NO donor and a triphenylphosphonium (TPP) moiety for targeting mitochondria. When irradiated by light, the constructed nanoparticles undergo rapid structural transformation from nanosphere to nanorod, enabling to achieve a significantly higher intratumoral accumulation by 3.26 times compared to that without light irradiation. More importantly, the conversion of generated NO and reactive oxygen species (ROS) in a light-responsive way to peroxynitrite anions (ONOO) with higher cytotoxicity enables NO to sensitize PDT in cancer treatment. Both and studies demonstrate that NO sensitized PDT based on the well-designed transformable nanoparticles enables to eradicate tumors efficiently. The light-triggered transformable nanoplatform developed in this work provides a new strategy for enhanced intratumoral retention and improved therapeutic outcome.
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http://dx.doi.org/10.1016/j.bioactmat.2021.09.035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8783071PMC
June 2022

Acid-Degradable Hydrogen-Generating Metal-Organic Framework for Overcoming Cancer Resistance/Metastasis and Off-Target Side Effects.

Adv Sci (Weinh) 2022 04 31;9(10):e2101965. Epub 2022 Jan 31.

School of Biomedical Engineering, Health Science Center, Shenzhen University, Shenzhen, Guangdong, 518060, China.

The development of stimuli-responsively degradable porous carriers for both controlled drug release and high biosafety is vitally important to their clinical translation, but still challenging at present. A new type of porphyrin-iron metal organic framework (Fe-MOF) nanocrystals is engineered here as acid-degradable drug carrier and hydrogen donor by the coordination between porphyrin and zero-valence Fe atom. Fe-MOF nanocrystals exhibit excellent acid-responsive degradation for H generation and simultaneous release of the loaded drug for combined hydrogen-chemotherapy of cancer multidrug resistance (MDR) and metastasis and for local hydrogen eradication of the off-target induced toxic side effects of the drug to normal cells/tissues. Mechanistically, released H assists chemotherapeutic drug to efficiently inhibit cancer metastasis by immunoactivating intratumoral M1-phenotype macrophages and consequently downregulating the expression of metastasis-related matrix metalloproteinase-2 (MMP-2) and can also downregulate the expressions of both P-glycoprotein (P-gp) protein and adenosine triphosphate (ATP) in MDR cancer cells to sensitize chemotherapeutic drug for enhanced damage to mitochondria and DNA. High anti-MDR/antimetastasis efficacies and high biocompatibility endow Fe-MOF nanocrystals and the Fe-MOF-based nanomedicine with high potential for clinical translation.
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http://dx.doi.org/10.1002/advs.202101965DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8981430PMC
April 2022

Changes of Host Immunity Mediated by IFN-γ CD8 T Cells in Children with Adenovirus Pneumonia in Different Severity of Illness.

Viruses 2021 11 28;13(12). Epub 2021 Nov 28.

Center Laboratory, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510120, China.

The host immunity of patients with adenovirus pneumonia in different severity of illness is unclear. This study compared the routine laboratory tests and the host immunity of human adenovirus (HAdV) patients with different severity of illness. A co-cultured cell model in vitro was established to verify the T cell response in vitro. Among 140 patients with confirmed HAdV of varying severity, the number of lymphocytes in the severe patients was significantly reduced to 1.91 × 10/L compared with the healthy control (3.92 × 10/L) and the mild patients (4.27 × 10/L). The levels of IL-6, IL-10, and IFN-γ in patients with adenovirus pneumonia were significantly elevated with the severity of the disease. Compared with the healthy control (20.82%) and the stable patients (33.96%), the percentage of CD8 T cells that produced IFN-γ increased to 56.27% in the progressing patients. Adenovirus infection increased the percentage of CD8 T and CD4 T cells that produce IFN-γ in the co-culture system. The hyperfunction of IFN-γ CD8 T cells might be related to the severity of adenovirus infection. The in vitro co-culture cell model could also provide a usable cellular model for subsequent experiments.
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http://dx.doi.org/10.3390/v13122384DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8708941PMC
November 2021

An Activity-Based Ratiometric Fluorescent Probe for In Vivo Real-Time Imaging of Hydrogen Molecules.

Angew Chem Int Ed Engl 2022 02 14;61(9):e202114594. Epub 2022 Jan 14.

Center of Hydrogen Science, Shanghai Jiao Tong University, Shanghai, 200240, China.

To reveal the biomedical effects and mechanisms of hydrogen molecules urgently needs hydrogen molecular imaging probes as an imperative tool, but the development of these probes is extremely challenging. A catalytic hydrogenation strategy is proposed to design and synthesize a ratiometric fluorescent probe by encapsulating Pd nanoparticles and conjugating azido-/coumarin-modified fluorophore into mesoporous silica nanoparticles, realizing in vitro and in vivo fluorescence imaging of hydrogen molecules. The developed hydrogen probe exhibits high sensitivity, rapid responsivity, high selectivity and low detection limit, enabling rapid and real-time detection of hydrogen molecules both in cells and in the body of animal and plant. By application of the developed fluorescent probe, we have directly observed the super-high transmembrane and ultrafast transport abilities of hydrogen molecules in cells, animals and plants, and discovered in vivo high diffusion of hydrogen molecules.
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http://dx.doi.org/10.1002/anie.202114594DOI Listing
February 2022

Primary Brainstem Hemorrhage: A Review of Prognostic Factors and Surgical Management.

Front Neurol 2021 10;12:727962. Epub 2021 Sep 10.

Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Primary brainstem hemorrhage (PBSH) is the most fatal subtype of intracerebral hemorrhage and is invariably associated with poor prognosis. Several prognostic factors are involved, of which the two most predominant and consistent are the initial level of consciousness and hemorrhage size. Other predictors, such as age, hyperthermia, and hydrocephalus, are generally not dependable indicators for making prognoses. Scoring systems have now been developed that can predict mortality and functional outcomes in patients suffering from PBSH, which can thus guide treatment decision-making. A novel grading scale, entitled "the new primary pontine hemorrhage (PPH) score," represents the latest approach in scoring systems. In this system, patients with a score of 2-3 points appear to benefit from surgical management, although this claim requires further verification. The four main surgical options for the treatment of PBSH are craniotomy, stereotactic hematoma puncture and drainage, endoscopic hematoma removal, and external ventricular drainage. Nevertheless, the management of PBSH still primarily involves conservative treatment methods and surgery is generally not recommended, according to current practice. However, the ongoing clinical trial, entitled Safety and Efficacy of Surgical Treatment in Severe Primary Pontine Hemorrhage Evacuation (STIPE), should provide additional evidence to support the surgical treatment of PBSH. Therefore, we advocate the update of epidemiological data and re-evaluation of PBSH treatment in a contemporary context.
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http://dx.doi.org/10.3389/fneur.2021.727962DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8460873PMC
September 2021

Inhibition of enterovirus 71 infection by polysaccharides extracted from Picochlorum sp. 122 via the AKT and ATM/ATR signaling pathways.

Arch Virol 2021 Dec 18;166(12):3269-3274. Epub 2021 Sep 18.

Center Laboratory, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510120, China.

Enterovirus 71 (EV71) poses a major threat to public health globally due to severe and even fatal hand, foot, and mouth disease (HFMD). However, no effective antiviral agents are available to treat HFMD caused by this virus. Polysaccharides have been shown to exhibit antiviral activity, and polysaccharides extracted from Picochlorum sp. 122 (PPE) could potentially be used to treat HFMD, but reports on their antiviral activity are limited. In this study, the antiviral activity of PPE against EV71 was verified in Vero cells. PPE was shown to limit EV71 infection, as demonstrated using an MTT assay and by observing the cellular cytopathic effect. In addition, a decrease in VP1 RNA and protein levels indicated that PPE effectively inhibits proliferation of EV71 in Vero cells. An annexin V affinity assay also indicated that PPE protects host cells from apoptosis through the AKT and ATM/ATR signalling pathways. These results demonstrate that PPE has potential as an antiviral drug to treat HFMD caused by EV71.
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http://dx.doi.org/10.1007/s00705-021-05229-1DOI Listing
December 2021

β-Catenin-CCL2 feedback loop mediates crosstalk between cancer cells and macrophages that regulates breast cancer stem cells.

Oncogene 2021 09 3;40(39):5854-5865. Epub 2021 Aug 3.

Guangzhou Key Laboratory of "Translational Medicine on Malignant Tumor Treatment", Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, Guangdong, China.

Breast cancer is the most frequently diagnosed cancer among women worldwide. Though advances in diagnosis and treatment have prolonged overall survival (OS) for patients with breast cancer, metastasis remains the major obstacles to improved survival for breast cancer patients. The existence of breast cancer stem cells (BCSCs) is a major reason underlying cancer metastasis and recurrence. Therefore, understanding the molecular pathways sustaining BCSC properties and targeting BCSCs will ultimately improve breast cancer treatments. In this study, we found that activation of β-Catenin directly regulated CCL2 expression at the transcriptional level, and in turn promoted macrophages infiltration and M2 polarization. Moreover, macrophages co-cultured with breast cancer cells showed a significant increase in CCL2 expression and promoted β-Catenin-induced BCSCs properties, whereas depletion of CCL2 by adding neutralizing antibodies suppressed BSCSs properties. In addition, we found that β-Catenin-mediated CCL2 secretion recruited macrophages into tumor microenvironment and promoted breast cancer growth and metastasis in vivo. Clinically, we observed a significant positive correlation between β-Catenin, CCL2 and CD163 expression, and increased expression of β-Catenin, CCL2 and CD163 predicted poor prognosis in breast cancer. Furthermore, pharmacological inhibition of CCR2 and β-Catenin synergistically suppressed BCSC properties and breast cancer growth. Collectively, our findings suggested that β-Catenin-mediated CCL2 secretion forms a paracrine feedback loop between breast cancer cells and macrophages, which in turn promotes BCSC properties and supports breast cancer growth and metastasis. Targeting β-Catenin/CCL2 signaling might be an effective strategy for breast cancer therapy.
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http://dx.doi.org/10.1038/s41388-021-01986-0DOI Listing
September 2021

[FOXC1 Knockdown Reverses Gefitinib Resistance in Non-small Cell Lung Cancer].

Zhongguo Fei Ai Za Zhi 2021 Aug 2;24(8):538-547. Epub 2021 Aug 2.

Department of Thoracic Surgery, Affiliated Cancer Hospital of 
Guangzhou Medical University, Guangzhou 510095, China.

Background: Lung cancer is the malignant tumor with the highest incidence and mortality in China, among which non-small cell lung cancer (NSCLC) accounts for about 80%. Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) targeted therapy has been playing an important role in treatment of NSCLC. However, unavoidable therapeutic resistance significantly limits the clinical efficacy of EGFR-TKI. As a key member of the forkhead box protein family, FOXC1 is aberrantly expressed in NSCLC and involved in NSCLC progression. The aim of this work is to investigate the effect and potential mechanism of FOXC1 on gefitinib resistance in NSCLC.

Methods: Western blot was performed to assess the expression of FOXC1 protein in HCC827/GR cells. Immunohistochemistry (IHC) assays were performed in human NSCLC tissues with gefitinib resistance. HCC827/GR cells were transfected with shRNA specifically targeting FOXC1 mRNA and stable cell lines were established. The effects of FOXC1 on cell viability and apoptosis were analyzed using a new methyl thiazolyl tetrazolium assay (MTS assay) and flow cytometry. Self-renewal ability was determined by mammosphere-formation analysis. Quantitative real-time PCR (qRT-PCR) and Western blot were employed to detect the expression of SOX2, Nanog, OCT4 and CD133. Flow cytometry analysis were further used to detect the level of CD133. IHC assays were used to detect the levels of SOX2 and CD133 in NSCLC tissues with genfitiinb resistance. Correlations of the expressions of FOXC1, CD133 and SOX2 with each other in lung adenocarcinoma samples were analyzed based on The Cancer Genome Atlas (TCGA) database.

Results: The expression of FOXC1 is significantly increased in HCC827/GR cells compared with HCC827 cells (P<0.05). IHC results showed FOXC1 was highly expressed in NSCLC tissues with gefitinib resisitance. Knockdown of FOXC1 significantly increased the sensitivity of HCC827/GR cells to gefitinib. The cell viability was decreased and the apoptosis was promoted (P<0.05). Moreover, FOXC1 knockdown apparently inhibited the expression of SOX2 and CD133, and decreased the mammosphere-formation capacity in HCC827/GR cells. In NSCLC tissues with gefitinib resistance, the expressions of SOX2 and CD133 were significantly higher compared with gefitinib-sensitive tissues (P<0.01). Meanwhile, the expressions of FOXC1, CD133 and SOX2 with each other were positively correlated (P<0.05).

Conclusions: FOXC1 could increase gefitinib resitance in NSCLC, by which mechanism is related to the regulation of cancer stem cell properties.
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http://dx.doi.org/10.3779/j.issn.1009-3419.2021.103.11DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8387653PMC
August 2021

Curcumin induced G2/M cycle arrest in SK-N-SH neuroblastoma cells through the ROS-mediated p53 signaling pathway.

J Food Biochem 2021 09 31;45(9):e13888. Epub 2021 Jul 31.

Department of Pediatric Urology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.

Neuroblastoma (NB) is a solid tumor in the nervous system and has a high mortality rate in children. Curcumin has well-characterized anticancer properties, while there is no effective method in clinical treatment. MTT assays revealed that curcumin dramatically inhibited the proliferation of SK-N-SH cells. Compared with the control group, curcumin markedly restrained the migration of SK-N-SH cells. Curcumin induced SK-N-SH cell apoptosis by G2/M cycle arrest and activated caspase-3 activity. Furthermore, curcumin promoted the overproduction of intracellular ROS and apoptosis induced by activating p53 and Bcl-2 signal pathways. This finding demonstrated the application of curcumin is an effective strategy for the therapeutics of NB.
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http://dx.doi.org/10.1111/jfbc.13888DOI Listing
September 2021

Heptazoline exerts antiproliferative effects on human melanoma cells by inducing apoptosis, cell cycle arrest and targeting MAPK signalling pathway.

J BUON 2021 May-Jun;26(3):1184

Department of Plastic Surgery, Zhongnan Hospital of Wuhan University, Wuhan , Hubei , 430071, China.

The Editors of JBUON issue an Expression of Concern to 'Heptazoline exerts antiproliferative effects on human melanoma cells by inducing apoptosis, cell cycle arrest and targeting MAPK signalling pathway', by Wei Zhou, Ling Zhou, Min Wang, Zeming Liu, Danyang Chen, Liang Guo; JBUON 2020;25(1):479-484; PMID: 32277672. Following the publication of the above article, readers drew to our attention that part of the data was possibly unreliable. We sent emails to the authors with a request to provide the raw data to prove the originality, but received no reply. Therefore, as we continue to work through the issues raised, we advise readers to interpret the information presented in the article with due caution. We thank the readers for bringing this matter to our attention. We apologize for any inconvenience it may cause.
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December 2021

Behavioral Assessment of Sensory, Motor, Emotion, and Cognition in Rodent Models of Intracerebral Hemorrhage.

Front Neurol 2021 17;12:667511. Epub 2021 Jun 17.

Department of Human Anatomy, College of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China.

Intracerebral hemorrhage (ICH) is the second most common type of stroke and has one of the highest fatality rates of any disease. There are many clinical signs and symptoms after ICH due to brain cell injury and network disruption resulted from the rupture of a tiny artery and activation of inflammatory cells, such as motor dysfunction, sensory impairment, cognitive impairment, and emotional disturbance, etc. Thus, researchers have established many tests to evaluate behavioral changes in rodent ICH models, in order to achieve a better understanding and thus improvements in the prognosis for the clinical treatment of stroke. This review summarizes existing protocols that have been applied to assess neurologic function outcomes in the rodent ICH models such as pain, motor, cognition, and emotion tests. Pain tests include mechanical, hot, and cold pain tests; motor tests include the following 12 types: neurologic deficit scale test, staircase test, rotarod test, cylinder test, grid walk test, forelimb placing test, wire hanging test, modified neurologic severity score, beam walking test, horizontal ladder test, and adhesive removal test; learning and memory tests include Morris water maze, Y-maze, and novel object recognition test; emotion tests include elevated plus maze, sucrose preference test, tail suspension test, open field test, and forced swim test. This review discusses these assessments by examining their rationale, setup, duration, baseline, procedures as well as comparing their pros and cons, thus guiding researchers to select the most appropriate behavioral tests for preclinical ICH research.
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http://dx.doi.org/10.3389/fneur.2021.667511DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8248664PMC
June 2021
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