Publications by authors named "Guoyan Liu"

91 Publications

Digestion and absorption properties of Lycium barbarum polysaccharides stabilized selenium nanoparticles.

Food Chem 2021 Nov 19:131637. Epub 2021 Nov 19.

College of Food Science and Engineering, Yangzhou University, Yangzhou 225127, China. Electronic address:

In the present study, the digestion and absorption properties of Lycium barbarum polysaccharides stabilized selenium nanoparticles (LBP-SeNPs) were investigated. The results showed that selenium nanoparticles (SeNPs) exhibited a higher selenium release rate than LBP-SeNPs (p<0.05) after being digested in the stages of oral cavity, stomach and intestine. During the digestion process, the particle size of the LBP-SeNPs and SeNPs were both significantly increased, but the particle size of LBP-SeNPs was significantly smaller than that of SeNPs. The results of TEM further indicated that LBP-SeNPs can better maintain the morphology and properties of nanoparticles. Besides, the experiments of the intestinal sac model showed that LBP-SeNPs can better promote the absorption of selenium in various parts (duodenum, jejunum and ileum) of the intestine. Therefore, the LBP can help to improve the structural stability of SeNPs in the digestion process and improve the bioavailability of selenium.
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http://dx.doi.org/10.1016/j.foodchem.2021.131637DOI Listing
November 2021

Endometriosis-associated Ovarian Clear Cell Carcinoma: A Special Entity?

Authors:
Yue Sun Guoyan Liu

J Cancer 2021 23;12(22):6773-6786. Epub 2021 Sep 23.

Department of Gynecology and Obstetrics, Tianjin Medical University General Hospital, Tianjin, 300052, China.

Endometriosis is an estrogen-dependent disease, which serves as a precursor of ovarian cancer, especially clear cell carcinoma (OCCC) and endometrial carcinoma. Although micro-environmental factors such as oxidative stress, immune cell dysfunction, inflammation, steroid hormones, and stem cells required for malignant transformation have been found in endometriosis, the exact carcinogenic mechanism remains unclear. Recent research suggest that many putative driver genes and aberrant pathways including ARID1A mutations, PIK3CA mutations, MET activation, HNF-1β activation, and miRNAs dysfunction, play crucial roles in the malignant transformation of endometriosis to OCCC. The clinical features of OCCC are different from other histological types. Patients usually present with a large, unilateral pelvic mass, and occasionally have thromboembolic vascular complications. OCCC patients are easier to be resistant to chemotherapy, have a worse prognosis, and are usually difficult to treat. To improve the survival of OCCC patients, it is necessary to better understand its specific carcinogenic mechanism and explore new treatment strategy, including molecular target.
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http://dx.doi.org/10.7150/jca.61107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8518018PMC
September 2021

Antioxidant capacity of phenolic compounds separated from tea seed oil in vitro and in vivo.

Food Chem 2022 Mar 15;371:131122. Epub 2021 Sep 15.

College of Food Science and Engineering, Yangzhou University, 225127 Yangzhou, Jiangsu Province, China. Electronic address:

Tea seed oil is rich in phenols with good antioxidant capacity. However, the antioxidant capacity evaluation of tea seed oil polyphenols is not deep enough, which mainly focusing on the evaluation of the chemical system. Thirty-nine phenols were tentatively identified by UPLC-ESI-MS/MS analysis, including flavonoids and phenolic acids. The antioxidant capacity of phenol extracts was investigated in vitro and in vivo. The chemical assays showed the extracts had good proton and electron transfer capabilities. The CAA assay indicated the IC of the extracts was 77.93 ± 4.80 µg/mL and cell antioxidant capacity of the extracts was 101.05 ± 6.70 μmol·QE/100 g of oil. The animal experiments suggested phenol extracts could significantly improve the organ index, reduce malondialdehyde content, and increase superoxide dismutase, glutathione peroxidase and total antioxidant capacity (p < 0.05). This study was contributed to the antioxidant capacity of phenol extracts of tea seed oil by comprehensive evaluation.
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http://dx.doi.org/10.1016/j.foodchem.2021.131122DOI Listing
March 2022

Cyclo-γ-polyglutamic acid-coated dual-responsive nanomicelles loaded with doxorubicin for synergistic chemo-photodynamic therapy.

Biomater Sci 2021 Sep 2;9(17):5977-5987. Epub 2021 Aug 2.

Department of Marine Biomedicine and Polar Medicine, Naval Special Medical Center, Naval Medical University, Shanghai 200433, China.

Nanodrug delivery systems have been used extensively to improve the tumor-targeting ability and reduce the side effects of anticancer drugs. In this study, nanomicelles responsive to dual stimuli were designed and developed as drug carriers for delivering doxorubicin (DOX). The hydrophobic group of the nanomicelles was composed of the photosensitizer protoporphyrin IX (PpIX) and the disulfide bond-containing alpha-lipoic acid (LA); the hydrophilic group was made up of the nuclear localization signal (NLS, CGGGPKKKRKVGG) peptide with a lysine linker. Furthermore, anionic cyclo-γ-polyglutamic acid (cyclo-γ-PGA) was coated on the surface of the cationic micelles to construct a multifunctional drug delivery system ([email protected]γ-PGA). Cyclo-γ-PGA, as a biological coating material, notably improved the stability of the cationic micelles by reducing nonspecific reactions with anionic groups. Additionally, the cyclo-γ-PGA coating mediated active tumor targeting and enhanced the cellular uptake of micelles via the γ-glutamyl transpeptidase (GGT) pathway. The integrated micelles not only achieved photochemical internalization (PCI) and photodynamic therapy (PDT) via light-activated reactive oxygen species (ROS) but also realized controlled intracellular drug release via the glutathione (GSH)-responsive disulfide-bond cleavage. As a result, [email protected]γ-PGA exhibited excellent synergistic chemo-photodynamic antitumor activity and fewer side effects than other therapies both in vitro and in vivo. In conclusion, this new dual-responsive drug delivery system ([email protected]γ-PGA) with improved stability and enhanced tumor-targeting ability may facilitate the development of high-efficiency and low-toxicity nanotherapeutic approaches.
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http://dx.doi.org/10.1039/d1bm00713kDOI Listing
September 2021

Natural Anti-Inflammatory Compounds as Drug Candidates for Inflammatory Bowel Disease.

Front Pharmacol 2021 14;12:684486. Epub 2021 Jul 14.

School of Pharmaceutical Sciences Xiamen University, Xiamen, China.

Inflammatory bowel disease (IBD) represents chronic recurrent intestinal inflammation resulting from various factors. Crohn's disease (CD) and ulcerative colitis (UC) have been identified as the two major types of IBD. Currently, most of the drugs for IBD used commonly in the clinic have adverse reactions, and only a few drugs present long-lasting treatment effects. Moreover, issues of drug resistance and disease recurrence are frequent and difficult to resolve. Together, these issues cause difficulties in treating patients with IBD. Therefore, the development of novel therapeutic agents for the prevention and treatment of IBD is of significance. In this context, research on natural compounds exhibiting anti-inflammatory activity could be a novel approach to developing effective therapeutic strategies for IBD. Phytochemicals such as astragalus polysaccharide (APS), quercetin, limonin, ginsenoside Rd, luteolin, kaempferol, and icariin are reported to be effective in IBD treatment. In brief, natural compounds with anti-inflammatory activities are considered important candidate drugs for IBD treatment. The present review discusses the potential of certain natural compounds and their synthetic derivatives in the prevention and treatment of IBD.
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http://dx.doi.org/10.3389/fphar.2021.684486DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8316996PMC
July 2021

Injectable Nanosponge-Loaded Pluronic F127 Hydrogel for Pore-Forming Toxin Neutralization.

Int J Nanomedicine 2021 23;16:4239-4250. Epub 2021 Jun 23.

Department of Marine Biomedicine and Polar Medicine, Naval Special Medical Center, Naval Medical University, Shanghai, 200433, People's Republic of China.

Purpose: Pore-forming toxins (PFTs) perform important functions during bacterial infections. Among various virulence-targeting therapies, nanosponges (NSs) have excellent neutralization effects on multiple PFTs. To enhance treatment efficacy, NSs tend to be incorporated into other biomaterials, such as hydrogels.

Methods: In the present work, red blood cell (RBC) vesicles were harvested to wrap polymer nanoparticles, leading to the formation of NSs, and the optimal Pluronic F127 hydrogel concentration was determined for gelation. Then, a novel detoxification system was constructed by incorporating NSs into an optimized Pluronic F127 hydrogel (NS-pGel). Next, the system was characterized by rheological and sustained release behavior as well as micromorphology. Then, the in vitro neutralization effect of NS-pGel on various PFTs was examined by a hemolysis protocol. Finally, therapeutic and prophylactic detoxification efficiency was evaluated in a mouse subcutaneous infection model in vivo.

Results: A thermosensitive, injectable detoxification system was successfully constructed by loading NSs into a 30% Pluronic F127 hydrogel. Characterization results demonstrated that the NS-pGel hybrid system sustained an ideal fluidity and viscosity at lower temperatures but exhibited a quick sol-gel transition capacity near body temperature. In addition, this hybrid system had a sustained release behavior accompanied by good biocompatibility and biodegradability. Finally, the NS-pGel system showed neutralization effects similar to those of NSs both in vitro and in vivo, indicating a good preservation of NS functionality.

Conclusion: In conclusion, we constructed a novel temperature-sensitive detoxification system with good biocompatibility and biodegradability, which may be applied to the clinical treatment of PFT-induced local lesions and infections.
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http://dx.doi.org/10.2147/IJN.S315062DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8238402PMC
July 2021

B7 homolog 6 promotes the progression of cervical cancer.

Exp Ther Med 2021 Jul 18;22(1):774. Epub 2021 May 18.

Department of Gynecology, The Second Hospital of Tianjin Medical University, Tianjin 300211, P.R. China.

B7 homolog 6 (B7-H6) was recently discovered to act as a co-stimulatory molecule. In particular, the expression of B7-H6 has been found to play an important biological role in several types of tumors. The aim of the present study was to determine the role of B7-H6 in cervical cancer. Immunohistochemistry was used to analyze the expression levels of B7-H6 in cervical precancerous and cancerous tissues. Furthermore, the expression of B7-H6 was knocked down in HeLa cells using short hairpin RNA and the effects of B7-H6 on HeLa cell proliferation, migration and invasion were determined using Cell Counting Kit-8, colony formation, wound healing and Transwell invasion assays, respectively. In addition, flow cytometry was used to analyze the levels of cell apoptosis and the cell cycle distribution. The results of the immunohistochemical staining revealed that the expression levels of B7-H6 were upregulated in cervical lesions. Furthermore, the expression levels of B7-H6 were positively associated with the clinical stage of the cervical lesions. B7-H6 knockdown suppressed the invasive, migratory and proliferative abilities of HeLa cells, and promoted G1 cell cycle arrest and apoptosis. In conclusion, the findings of the present study suggested that B7-H6 may serve as a novel oncogene and may hold promise as a potential therapeutic target for cervical cancer.
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http://dx.doi.org/10.3892/etm.2021.10206DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8145428PMC
July 2021

Dual Modal Imaging-Guided Drug Delivery System for Combined Chemo-Photothermal Melanoma Therapy.

Int J Nanomedicine 2021 18;16:3457-3472. Epub 2021 May 18.

Shandong Engineering Research Center for Smart Materials and Regenerative Medicine, Weifang, 261053, People's Republic of China.

Purpose: Malignant melanoma is one of the most devastating types of cancer with rapid relapse and low survival rate. Novel strategies for melanoma treatment are currently needed to enhance therapeutic efficiency for this disease. In this study, we fabricated a multifunctional drug delivery system that incorporates dacarbazine (DTIC) and indocyanine green (ICG) into manganese-doped mesoporous silica nanoparticles (MSN(Mn)) coupled with magnetic resonance imaging (MRI) and photothermal imaging (PI), for achieving the superior antitumor effect of combined chemo-photothermal therapy.

Materials And Methods: MSN(Mn) were characterized in terms of size and structural properties, and drug loading and release efficiency MSN(Mn)-ICG/DTIC were analyzed by UV spectra. Photothermal imaging effect and MR imaging effect of MSN(Mn)-ICG/DTIC were detected by thermal imaging system and 3.0 T MRI scanner, respectively. Then, the combined chemo-phototherapy was verified in vitro and in vivo by morphological evaluation, ultrasonic and pathological evaluation.

Results: The as-synthesized MSN(Mn) were characterized as mesoporous spherical nanoparticles with 125.57±5.96 nm. MSN(Mn)-ICG/DTIC have the function of drug loading-release which loading ratio of ICG and DTIC could reach to 34.25±2.20% and 50.00±3.24%, and 32.68±2.10% of DTIC was released, respectively. Manganese doping content could reach up to 65.09±2.55 wt%, providing excellent imaging capability in vivo which the corresponding relaxation efficiency was 14.33 mMs. And outstanding photothermal heating ability and stability highlighted the potential biomedical applicability of MSN(Mn)-ICG/DTIC to kill cancer cells. Experiments by A375 melanoma cells and tumor-bearing mice demonstrated that the compound MSN(Mn)-ICG/DTIC have excellent biocompatibility and our combined therapy platform delivered a superior antitumor effect compared to standalone treatment in vivo and in vitro.

Conclusion: Our findings demonstrate that composite MSN(Mn)-ICG/DTIC could serve as a multifunctional platform to achieve a highly effective chemo-photothermal combined therapy for melanoma treatment.
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http://dx.doi.org/10.2147/IJN.S306269DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8144848PMC
June 2021

Effect of palliative care on the anxiety, depression and sleep quality in primary caregivers of elderly patients with terminal cancer.

Am J Transl Res 2021 15;13(4):3738-3744. Epub 2021 Apr 15.

Department of Surgery, Huiqiao Medical Center, Nanfang Hospital, Southern Medical University Guangzhou, Guangdong Province, China.

Objective: To explore the effect of palliative care on the psychological well-being and sleep quality of the primary caregivers of elderly patients with terminal cancer.

Methods: In this prospective study, a total of 102 elderly patients with terminal cancer and their primary caregivers were randomly divided into a study group and a control group of 51 patients each by a random number table. The control group was given routine end-of-life care and the study group was given palliative care. In this study, we compared adverse mood, sleep quality, psychological stress and satisfaction with care among primary caregivers before and after the intervention, as well as changes in patients' quality of life.

Results: The Hamilton Anxiety Scale (HAMA), the Hamilton Depression Scale (HAMD), the Pittsburgh Sleep Quality Index (PSQI), and RSS scores of the primary caregiver were significantly lower in both groups after the intervention, and significantly lower in the study group (all P<0.05). The Generic Quality of Life Inventory-74 (GQOLI-74) scores were significantly higher in both groups after the intervention, and significantly higher in the study group (all P<0.05). In addition, the primary caregiver's satisfaction with care was significantly higher in the study group than that in the control group (96.08% vs. 82.35%, P<0.05).

Conclusion: Palliative care for patients with terminal cancer can be effective in alleviating the poor psychological well-being of the primary caregivers, improving their sleep quality as well as improving nursing satisfaction and patients' quality of life.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8129337PMC
April 2021

Circular RNA circHECTD1 prevents Diosbulbin-B-sensitivity via miR-137/PBX3 axis in gastric cancer.

Cancer Cell Int 2021 May 17;21(1):264. Epub 2021 May 17.

Institute of Gastrointestinal Oncology, School of Medcine, Xiamen University, Xiamen, Fujian, 361004, China.

Backgrounds: Gastric cancer (GC) is general disease in human digestive system with malignancy. Emerging findings indicated that hsa_circ_0031452 (circHECTD1) was strictly associated with carcinogenesis. Nevertheless, the role of circHECTD1 in drug-resistance still needed to be explained.

Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to examine the expression profiles of circHECTD1, microRNA (miR)-137, and pre-leukemia transcription factor 3 (PBX3). The function of circHECTD1 in tumorigenesis was evaluated via xenograft tumor model. The IC of Diosbulbin-B (DB) was detected using Cell Counting Kit-8 (CCK8). Cell-cycle and apoptosis were reckoned by flow cytometry. Besides, western blot was administrated to reckon the levels of PBX3 and cell apoptotic indicators. Moreover, the interrelation between miR-137 and circHECTD1 or PBX3 was expounded by dual-luciferase reporter, RNA immunoprecipitation (RIP) and RNA pull down assays.

Results: We uncovered that circHECTD1 was ectopically up-regulated in GC tissues and cells. CircHECTD1 deficiency sensitized DB-treatment in DB-evoked AGS and HGC-27 cells. In vivo assay, circHECTD1 silencing led to the tumor reduction. Also, circHECTD1 served as miR-137 sponge in a sequence-complementary manner. Furthermore, transfection of miR-137 inhibitor markedly eliminated circHECTD1 absence-mediated promotion of DB-sensitivity in GC cells. Moreover, PBX3, a target of miR-137, play a DB-resistant role in GC cells. Fascinatingly, the deletion of PBX3 reversed the impact of miR-137 repression and circHECTD1 knockdown on DB-sensitivity in vitro.

Conclusions: CircHECTD1 served as an oncogene by a novel miR-137/PBX3 axis, which might supply an underlying biomarker for the diagnosis and prognosis of GC management.
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http://dx.doi.org/10.1186/s12935-021-01957-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8127237PMC
May 2021

is involved in the formation of polyploid cancer cells and the response to paclitaxel.

Ann Transl Med 2021 Apr;9(8):693

Department of Gynecology and Obstetrics, Tianjin Medical University General Hospital, Tianjin, China.

Background: Most human solid tumors are aneuploid; at the same time, polyploid cancer cells are found to be resistant to radiotherapy and chemotherapy and have a poor prognosis. The transforming growth factor beta induction () protein plays important roles in the development of tumors, depending on the cancer of origin.

Methods: In this study, we established polyploid clones of breast cancer treated with nocodazole. The drug sensitivity was measured by MTT assay. Western blot analysis was used to detect the expression of protein in polyploid clones. The effects of paclitaxel on apoptosis, cell cycle and DNA ploidy were analyzed by flow cytometry. protein expression was performed in samples from patients with epithelial ovarian tumors by immunohistochemical staining.

Results: We found that compared with the MDA-MB-231 cell line, the expression of in the HGF1806 cell line was relatively higher. In addition, compared with its parental cells, showed relatively low expression in the polyploid breast cancer cell line T-MDA-MB-231. Compared with the empty vector, under paclitaxel treatment, the over-expression of in MDA-MB-231 and T-MDA-MB-231 both showed a higher growth inhibition rate. After nocodazole treatment, the over-expression of in MDF-MB-231 cells proved that the expression of tetraploid cells was lower compared to the control. The positive rate of expression in ovarian cancer specimens before chemotherapy was 33.3% (5/15), which was higher than the positive rate of expression in ovarian cancer specimens matched with relapsed specimens after treatment (0%, 0/15).

Conclusions: can increase the sensitivity of paclitaxel in polyploid cancer cells and participate in the formation of polyploidy in MDA-MB-231 induced by nocodazole. This newly recognized role of provides further insight into the pathogenesis of polyploid cancer and identifies potential new therapeutic targets.
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http://dx.doi.org/10.21037/atm-21-1698DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8105995PMC
April 2021

DNA damage response and PD-1/PD-L1 pathway in ovarian cancer.

DNA Repair (Amst) 2021 06 1;102:103112. Epub 2021 Apr 1.

Department of Gynecology and Obstetrics, Tianjin Medical University General Hospital, No. 154 Anshan Road, Tianjin, 300052, China; Tianjin Key Laboratory of Female Reproductive Health and Eugenics, Tianjin, 300052, China. Electronic address:

Ovarian cancer has a poor prognosis due to drug resistance, relapse and metastasis. In recent years, immunotherapy has been applied in numerous cancers clinically. However, the effect of immunotherapy monotherapy in ovarian cancer is limited. DNA damage response (DDR) is an essential factor affecting the efficacy of tumor immunotherapy. Defective DNA repair may lead to carcinogenesis and tumor genomic instability, but on the other hand, it may also portend particular vulnerability of tumors and can be used as biomarkers for immunotherapy patient selection. Programmed cell death 1 (PD-1)/programmed death-ligand 1 (PD-L1) pathway mediates tumor immune escape, which may be a promising target for immunotherapy. Therefore, further understanding of the mechanism of PD-L1 expression after DDR may help guide the development of immunotherapy in ovarian cancer. In this review, we present the DNA damage repair pathway and summarize how DNA damage repair affects the PD-1/PD-L1 pathway in cancer cells. And then we look for biomarkers that affect efficacy or prognosis. Finally, we review the progress of PD-1/PD-L1-based immunotherapy in combination with other therapies that may affect the DDR pathway in ovarian cancer.
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http://dx.doi.org/10.1016/j.dnarep.2021.103112DOI Listing
June 2021

Role of exosomes in the immune microenvironment of ovarian cancer.

Oncol Lett 2021 May 15;21(5):377. Epub 2021 Mar 15.

Department of Gynecology, Tianjin Medical University General Hospital, Tianjin 300052, P.R. China.

Exosomes are excretory vesicles that can deliver a variety of bioactive cargo molecules to the extracellular environment. Accumulating evidence demonstrates exosome participation in intercellular communication, immune response, inflammatory response and they even play an essential role in affecting the tumor immune microenvironment. The role of exosomes in the immune microenvironment of ovarian cancer is mainly divided into suppression and stimulation. On one hand exosomes can stimulate the innate and adaptive immune systems by activating dendritic cells (DCs), natural killer cells and T cells, allowing these immune cells exert an antitumorigenic effect. On the other hand, ovarian cancer-derived exosomes initiate cross-talk with immunosuppressive effector cells, which subsequently cause immune evasion; one of the hallmarks of cancer. Exosomes induce the polarization of macrophages in M2 phenotype and induce apoptosis of lymphocytes and DCs. Exosomes further activate additional immunosuppressive effector cells (myeloid-derived suppressor cells and regulatory T cells) that induce fibroblasts to differentiate into cancer-associated fibroblasts. Exosomes also induce the tumorigenicity of mesenchymal stem cells to exert additional immune suppression. Furthermore, besides mediating the intercellular communication, exosomes carry microRNAs (miRNAs), proteins and lipids to the tumor microenvironment, which collectively promotes ovarian cancer cells to proliferate, invade and tumors to metastasize. Studying proteins, lipids and miRNAs carried by exosomes could potentially be used as an early diagnostic marker of ovarian cancer for designing treatment strategies.
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http://dx.doi.org/10.3892/ol.2021.12638DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7988709PMC
May 2021

Synthesis, stability and anti-fatigue activity of selenium nanoparticles stabilized by Lycium barbarum polysaccharides.

Int J Biol Macromol 2021 May 4;179:418-428. Epub 2021 Mar 4.

College of Food Science and Engineering, Yangzhou University, Yang Zhou 225127, China. Electronic address:

Lycium barbarum polysaccharides (LBP) with different molecular weights (LBP1, LBP2 and LBP3) of 92,441 Da, 7714 Da, and 3188 Da were used as stabilizers and capping agents to prepare uniformly dispersed selenium nanoparticles (SeNPs), and determined the storage stability. In addition, the anti-fatigue activity of LBP-decorated SeNPs with the best stability (LBP1-SeNPs) was estimated by using forced swimming test. The results showed that LBP1-SeNPs exhibited smaller particle size and more excellent stability than those of LBP2-SeNPs and LBP3-SeNPs when the storage time was extended to 30 days, and the average particle size was maintained at about 105.4 nm. The exhaustion swimming time of all tested dose groups of LBP1-SeNPs was significantly longer than the control group (p < 0.05), and the high-dose group among them was even obviously longer than the positive group (p < 0.05). The results of glycogen, blood urea nitrogen (BUN), blood lactic acid (BLA), superoxide dismutase (SOD), and malondialdehyde (MDA) levels were further confirmed that LBP1-SeNPs could relieve fatigue by increasing the reserve of glycogen, enhancing antioxidant enzyme levels and regulating metabolic mechanism. These results demonstrated that LBP1-SeNPs could be developed as a potential anti-fatigue nutritional supplement.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.03.018DOI Listing
May 2021

High-Intensity Focused Ultrasound Combined With Gonadotropin-Releasing Hormone Agonist or Levonorgestrel-Releasing Intrauterine System in Treating Dysmenorrhea of Severe Adenomyosis.

J Comput Assist Tomogr 2021 Mar-Apr 01;45(2):224-231

From the Department of Gynaecology, General Hospital of Tianjin Medical University, Tianjin Medical University, Tianjin.

Objective: The objective of this study was to investigate the efficacy of high-intensity focused ultrasound (HIFU) combined with gonadotropin-releasing hormone agonist or levonorgestrel-releasing intrauterine system (LNG-IUS) in treating dysmenorrhea in patients with severe adenomyosis.

Methods: A retrospective analysis was performed on 243 patients diagnosed with severe adenomyosis. Patients were divided into H (received HIFU alone), H-G (received HIFU combined with gonadotropin-releasing hormone agonist), and H-L (received HIFU combined with LNG-IUS) groups. Their clinical results were compared at 3 months, 6 months, and 12 months after treatment.

Results: The effective rates of dysmenorrhea relief in the 3 groups after 3 months were 95.24% in the H group, 98.8% in the H-G group, and 94.74% in the H-L group; those after 6 months were 88.10% in the H group, 95.18% in the H-G group, and 84.21% in the H-L group; those after 12 months were 77.38% in the H group, 79.52% in the H-G group, and 96.05% in the H-L group. There was significant difference in effective rates of dysmenorrhea relief among 3 groups after 12 months of treatment, but not 3 or 6 months. In addition, at 12 months after treatment, there were significant differences in the efficacy of dysmenorrhea between patients of different ages or different ablation rates in group H. However, there was no significant difference in the H-G group and the H-L group.

Conclusions: High-intensity focused ultrasound alone is effective in alleviating the symptoms of dysmenorrhea in short term. However, HIFU combined with LNG-IUS improves the therapeutic effect for a longer period.
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http://dx.doi.org/10.1097/RCT.0000000000001138DOI Listing
April 2021

Inhibition of lncRNA-NEAT1 sensitizes 5-Fu resistant cervical cancer cells through de-repressing the microRNA-34a/LDHA axis.

Biosci Rep 2021 07;41(7)

Department of Obstetrics and Gynecology, Tianjin Medical University General Hospital, Tianjin 300170, China.

Cervical cancer is one of the most diagnosed malignancies among females. The 5-fluorouracil (5-Fu) is a widely used chemotherapeutic agent against diverse cancers. Despite the initially encouraging progresses, a fraction of cervical cancer patients developed 5-Fu resistance. We detected that nuclear-rich transcripts 1 (NEAT1) was significantly up-regulated in cervical cancer tissues and cell lines. Moreover, NEAT1 was positively associated with 5-Fu resistance. Furthermore, expression of NEAT1 was significantly up-regulated in 5-Fu resistant CaSki cervical cancer cells. Knocking down NEAT1 by shRNA dramatically promoted the sensitivity of 5-Fu resistant CaSki cells. We observed a negative correlation between long noncoding RNA (lncRNA)-NEAT1 and miR-34a in cervical cancer patient tissues. Overexpression of miR-34a significantly sensitized 5-Fu resistant cells. Bioinformatics analysis uncovered that NEAT1 functions as a competitive endogenous RNA (ceRNA) of miR-34a in cervical cancer cells via sponging it at multiple sites to suppress expression of miR-34a. This negative association between NEAT1 and miR-34a was further verified in cervical cancer tissues. We found the 5-Fu resistant cells displayed significantly increased glycolysis rate. Overexpression of miR-34a suppressed cellular glycolysis rate and sensitized 5-Fu resistant cells through direct targeting the 3'-untranslated region (UTR) of LDHA, a glycolysis key enzyme. Importantly, knocking down NEAT1 successfully down-regulated LDHA expressions and glycolysis rate of cervical cancer cells by up-regulating miR-34a, a process could be further rescued by miR-34a inhibition. Finally, we demonstrated inhibition of NEAT1 significantly sensitized cervical cancer cells to 5-Fu through the miR-34a/LDHA pathway. In summary, the present study suggests a new molecular mechanism for the NEAT1-mediated 5-Fu resistance via the miR-34a/LDHA-glycolysis axis.
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http://dx.doi.org/10.1042/BSR20200533DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8298262PMC
July 2021

Hsa_circ_0076305 induces migration-proliferation dichotomy in gastric cancer.

Oncol Lett 2021 Mar 21;21(3):220. Epub 2021 Jan 21.

Department of Gastrointestinal Surgery, Zhongshan Hospital of Xiamen University, Xiamen, Fujian 361004, P.R. China.

Recent studies have demonstrated that circular RNAs (circRNAs) play an important role in the development of gastric cancer (GC). The present study aimed to investigate the role of hsa_circ_0076305 (circPGC) in GC. The levels of circRNAs and mRNAs in AGS cell lines were detected via reverse transcription-quantitative PCR, and western blotting was performed to detect protein expression levels. Functional studies were explored by CCK8 assay and cell migration assay. Functional studies have indicated that circPGC orchestrates two cellular processes; it inhibits proliferation, and promotes migration and invasion in the GC AGS cell line, a phenomenon called 'migration-proliferation dichotomy', as well as epithelial-to-mesenchymal transition in AGS cells. In addition, circPGC degrades the extracellular matrix and basement membrane through matrix metallopeptidase (MMP)9 and MMP14, providing a microenvironment that facilitates cell migration. The results also demonstrated that circPGC expression is lower in clinical patients with later stages of GC, which is associated with poor prognosis. Taken together, these results suggest that circPGC exhibits migration-proliferation dichotomy during GC development, invasion and migration.
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http://dx.doi.org/10.3892/ol.2021.12481DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7859472PMC
March 2021

Incidence and detection of high microsatellite instability in colorectal cancer in a Chinese population: a meta-analysis.

J Gastrointest Oncol 2020 Dec;11(6):1155-1163

Department of Pathology, Guangdong Provincial Peoples' Hospital, Guangzhou, China.

Background: The 4 most common types of DNA mutations in tumors are single-nucleotide variations, insertion-deletion, fusion, and copy number variations. This is followed by microsatellite instability (MSI), which is known to trigger the development of MSI-high (MSI-H) cancer and is responsible for 300,000 new cases of cancer per year in China. We aim to conduct a meta-analysis based on a comparison between the positive rates of the National Cancer Institute (NCI) panel (also known as 2B3D NCI panel) and mononucleotide panels for the diagnosis of MSI in the Chinese population.

Methods: In the present meta-analysis, we searched the PubMed, Embase, Web of Science, CNKI, Wanfang, CQVIP, and CBM databases. MSI diagnosis studies by PCR and capillary electrophoresis were included to compare the incidence of MSI-H in colorectal cancer obtained from panels with different microsatellite markers. Egger's bias test was used to assess risk of bias.

Results: Seventeen articles were included, which used the Newcastle-Ottawa Scale (NOS) scale for quality evaluation. The NOS scores of the included documents were ≥7 points, and the quality of the documents met the requirements. The incidence of MSI-H detected by the 2B3D NCI panel was 13.5% [95% confidence interval (CI): 10.8-16.4, I=52.321%, P=0.026, n=10 studies including 2,681 participants], the incidence of MSI-H detected by the mononucleotide panels was 10.6% (95% CI: 7.1-14.7, I=81.147%, P=0.000, n=7 studies including 3,249 participants). This indicates that, in the Chinese population, the 2B3D NCI panel can detect 27.4% more MSI-H cancers than the mononucleotide panels, 54.7% more MSI-H cancers than the panel of 6 mononucleotides, and its sensitivity is comparable to that of Promega.

Conclusions: The findings of the meta-analysis demonstrated that, using the 2B3D NCI panel for MSI detection can avoid the underestimation of the incidence MSI-H in colorectal cancer and can be considered the most suitable panel for MSI detection in the Chinese population. The inclusion of only published data might be a potential source of publication bias.
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http://dx.doi.org/10.21037/jgo-20-487DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7807279PMC
December 2020

MicroRNA-506-3p increases the response to PARP inhibitors and cisplatin by targeting EZH2/β-catenin in serous ovarian cancers.

Transl Oncol 2021 Feb 22;14(2):100987. Epub 2020 Dec 22.

Department of Gynecology and Obstetrics, Tianjin Medical University General Hospital, Tianjin 300052, China. Electronic address:

Chemo-resistance is an important barrier to effective treatment of ovarian cancer. Poly (ADP-ribose) polymerase (PARP) inhibitors are currently promising targeted drugs used to treat BRCA-mutant ovarian cancer. Ovarian cancer patients with BRCA 1/2 mutations appear to benefit better from PARP inhibitors and chemotherapy. Understanding the mechanisms underlying PARP inhibitors and chemotherapy resistance is urgently needed. There is increasing evidence that microRNAs (miRNAs) are involved in drug resistance. MiR-506-3p is an effective inhibitor of the epithelial-to-mesenchymal transition (EMT), and can enhance chemotherapy and olaparib response in high-grade serous ovarian cancer (HGS-OvCa). Enhancer of Zeste Homolog 2 (EZH2) is considered as a direct target of miR-506-3p. The silencing of EZH2 mimics the inhibitory effects of miR-506-3p on chemo-resistance and olaparib response. Rescue of EZH2 prevented the functions of miR-506-3p. Moreover, EZH2 activates the β-catenin pathway. MiR-506-3p overexpression decreased the level of β-catenin, and the sensitivity to olaparib and cisplatin mediated by miR-506-3p was partially reversed by regulating β-catenin expression in ovarian cancer. Our results suggest that miR-506-3p increases response to PARP inhibitors and cisplatin in serous ovarian cancer by targeting EZH2/β-catenin signal pathway, which opens the possibility of using miR-506-3p overexpression as a potential therapeutic for ovarian cancer.
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http://dx.doi.org/10.1016/j.tranon.2020.100987DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7770486PMC
February 2021

Podocarpusflavone A inhibits cell growth of skin cutaneous melanoma by suppressing STAT3 signaling.

J Dermatol Sci 2020 Dec 17;100(3):201-208. Epub 2020 Oct 17.

Department of Dermatology, Weifang Medical University, Shandong, China. Electronic address:

Background: JAK2/STAT3 pathway is involved in the development and progression of melanoma once DNA damage is caused by environment and genetic factors.

Objective: Here, we aimed to identify novel inhibitor of JAK2/STAT3 pathway and reveal the underlying mechanisms.

Methods: Eighty MedChemExpress compounds were screened by using STAT3-Luc reporter in A375 cells. Podocarpusflavone A (PCFA) was identified as an inhibitor of STAT3, which was further verified in four melanoma cell lines. The anti-melanoma effects and mechanism of PCFA were examined and explored in melanoma cells and mouse xenograft models by using Western blot and cell-counting kit-8 assay.

Results: PCFA exhibited potent inhibitory effects on melanoma both in vitro and in vivo. PCFA inhibited the activation of STAT3 through suppressing the phosphorylation of JAK2, and then restrained cell cycle and induced apoptosis of melanoma cells.

Conclusion: PCFA inhibits melanoma growth via the inhibition of JAK2/STAT3 pathway, which provides a promising therapeutic strategies of melanoma treatment.
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http://dx.doi.org/10.1016/j.jdermsci.2020.10.008DOI Listing
December 2020

Relationship between age at menarche and chromosome numerical abnormalities in chorionic villus among missed abortions: A cross-sectional study of 459 women in China.

J Obstet Gynaecol Res 2020 Oct 1. Epub 2020 Oct 1.

Obstetrics and Gynecology Department, Tianjin Medical University General Hospital, Tianjin, China.

Aims: To assess the relationship between age at menarche and the numerical abnormalities of chorionic villi chromosomes in patients with missed abortion.

Methods: Unexplained miscarriage patients were admitted to an outpatient clinic in Tianjin Central Hospital of Gynecology Obstetrics, China. Embryonic villi tissues were collected aseptically after curettage. Chromosome analysis was performed subsequently using multiplex ligation-dependent probe amplification method.

Results: Among 459 cases of missed abortion, chromosome numerical abnormalities were found in 231 cases (50.33%). Autosomal trisomy occurs most frequently, with 16-trisomy being most common. Patients (age more than 35 years old) had more frequent miscarriages compared with those who were less than 35 years old. However, there was no statistically significant difference in chromosome numerical abnormalities. In addition, compared with patients less than 30 years old, women with age ≥ 30 years old had higher abortions frequency (P = 0.002), and the proportion of chromosome numeric abnormalities increased (P = 0.000). The number of patients with abnormal chromosomes is higher among patients whose age of menarche are less than 12 years old than that of patients whose age of menarche was over 12 years old (P = 0.003).

Conclusion: Chromosome numerical abnormalities are important cause of missed abortion. The incidence of chromosome numeric abnormalities increases among patients ≥30 years old. Besides, age of menarche is an important risk factor for chromosome numerical abnormalities.
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http://dx.doi.org/10.1111/jog.14499DOI Listing
October 2020

Full-range space-division multiplexing optical coherence tomography angiography.

Biomed Opt Express 2020 Aug 31;11(8):4817-4834. Epub 2020 Jul 31.

Department of Electrical and Computer Engineering, Lehigh University, 19 Memorial Drive West, Bethlehem, PA 18015, USA.

In this study, we demonstrated a full-range space-division multiplexing optical coherence tomography (FR-SDM-OCT) system. Utilizing the galvanometer-based phase modulation full-range technique, the total imaging range of FR-SDM-OCT can be extended to >20 mm in tissue, with a digitizer sampling rate of 500 MS/s and a laser sweeping rate of 100 kHz. Complex conjugate terms were suppressed in FR-SDM-OCT images with a measured rejection ratio of up to ∼46 dB at ∼1.4 mm depth and ∼30 dB at ∼19.4 mm depth. The feasibility of FR-SDM-OCT was validated by imaging Scotch tapes and human fingernails. Furthermore, we demonstrated the feasibility of FR-SDM-OCT angiography (FR-SDM-OCTA) to perform simultaneous acquisition of human fingernail angiograms from four positions, with a total field-of-view of ∼1.7 mm × ∼7.5 mm. Employing the full-range technique in SDM-OCT can effectively alleviate hardware requirements to achieve the long depth measurement range, which is required by SDM-OCT to separate multiple images at different sample locations. FR-SDM-OCTA creates new opportunities to apply SDM-OCT to obtain wide-field angiography of tissue samples free of labeling.
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http://dx.doi.org/10.1364/BOE.400162DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7449723PMC
August 2020

Interactions between dietary fiber and ferulic acid change the aggregation of glutenin, gliadin and glutenin macropolymer in wheat flour system.

J Sci Food Agric 2021 Mar 5;101(5):1979-1988. Epub 2020 Oct 5.

China-Canada Joint Lab of Food Nutrition and Health (Beijing), Beijing Advanced Innovation Center for Food Nutrition and Human Health, Beijing Engineering and Technology Research Center of Food Additives, Beijing Technology and Business University, Beijing, China.

Background: Glutenin macropolymer (GMP), glutenin and gliadin proteins are important indicators of the baking quality of dough. This study investigated the impacts of wheat bran and a mixture of ferulic acid (FA) and dietary fiber (DF) on the constitution of gluten proteins. Addition of wheat bran (100 and 150 g kg ) into gluten decreased the gliadin/glutenin ratio, while the addition of different amounts of FA + DF (C1 group: 20 g kg FA and 60 g kg DF; C2 group: 30 g kg FA and 90 g kg DF) had the opposite effect.

Results: The GMP contents of wheat bran groups (B1 group: 100 g kg ; B2 group: 150 g kg ) were similar to that of the control group, and disulfide bond contents were increased. However, both GMP and disulfide bond contents of FA + DF groups significantly decreased. The GMP gel properties and microstructures were destroyed after addition of wheat bran and FA + DF. The wheat bran and FA + DF additives induced different effects on the thermal properties and secondary structures of glutenin, gliadin and GMP.

Conclusions: The results suggest that the interaction mechanism of bran fractions and gluten proteins is not only related to the physicochemical properties of the additives, but also to interactions between the additives and the components of gluten protein. © 2020 Society of Chemical Industry.
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http://dx.doi.org/10.1002/jsfa.10814DOI Listing
March 2021

A comparative analysis of the proteomes and biological activities of the venoms from two sea snakes, Hydrophis curtus and Hydrophis cyanocinctus, from Hainan, China.

Toxicon 2020 Nov 29;187:35-46. Epub 2020 Aug 29.

Department of Marine Biomedicine and Polar Medicine, Naval Characteristic Medical Center, Naval Medical University, Shanghai, 200433, China. Electronic address:

We characterized and compared the venom protein profiles of Hydrophis curtus (synonyms: Lapemis hardwickii, Lapemis curtus and Hydrophis hardwickii) and Hydrophis cyanocinctus, the two representatives of medically important venomous sea snakes in Chinese waters using proteomic approaches. A total of 47 and 38 putative toxins were identified in H. curtus venom (HcuV) and H. cyanocinctus venom (HcyV), respectively, and these toxins could be grouped into 15 functional categories, mainly proteinases, phospholipases, three-finger toxins (3FTxs), lectins, protease inhibitors, ion channel inhibitors, cysteine-rich venom proteins (CRVPs) and snake venom metalloproteases (SVMPs). The constituent ratio of each toxin category varied between HcuV and HcyV with 3FTx (54% in HcuV/69% in HcyV) and PLA2 (38% in HcuV/22% in HcyV) unanimously ranked as the top two most abundant families. Both HcuV and HcyV exhibited relatively high lethality (LD values in mice of 0.34 μg/g and 0.24 μg/g, respectively), specific PLA2 activity and hemolytic activity. On the basis of several previous reports of HcuV and HcyV collected from other areas, these findings greatly expand our understanding of geographical variation and interspecies diversity of the two sea snake venoms and can provide a scientific basis for the development of specific sea snake antivenom in the future.
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http://dx.doi.org/10.1016/j.toxicon.2020.08.012DOI Listing
November 2020

A comparison between perpendicular and parallel plating methods for distal humerus fractures: A meta-analysis of randomized controlled trials.

Medicine (Baltimore) 2020 Jun;99(23):e19602

Department of Orthopedics, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Shandong, China.

Objective: To compare the clinical outcomes of perpendicular and parallel plating for the treatment of distal humerus fractures.

Methods: Two investigators independently searched PubMed, OVID, and ScienceDirect databases prior to April 2019, without any limitations on language or publication status. The outcomes were union time, range of motion of elbow, Mayo Elbow Performance Score, and postoperative complications. Two authors independently performed a methodological quality and risk of bias assessment using Cochrane collaboration's tool. Data analysis was performed with STATA version 13.0.

Results: Six randomized controlled trials with 305 participants were included. The present meta-analysis indicated that orthogonal plating was associated with a longer union time compared with parallel plating. There were no significant differences between the 2 groups regarding Elbow function, Mayo Elbow Performance Score, operation time, reduction quality, or postoperative complications.

Conclusion: Both parallel plating and orthogonal plating are considered to be effective methods when treating distal humerus fractures. The results of this study found that parallel plating is superior to orthogonal plating in humerus fracture healing.
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http://dx.doi.org/10.1097/MD.0000000000019602DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7306383PMC
June 2020

Integrated analysis of lymphocyte infiltration-associated lncRNA for ovarian cancer via TCGA, GTEx and GEO datasets.

PeerJ 2020 7;8:e8961. Epub 2020 May 7.

Department of Gynecology and Obstetrics, Tianjin Medical University General Hospital, Tianjin, China.

Background: Abnormal expression of long non-coding RNAs (lncRNA) play a significant role in the incidence and progression of high-grade serous ovarian cancer (HGSOC), which is a leading cause of mortality among gynecologic malignant tumor patients. In this study, our aim is to identify lncRNA-associated competing endogenous RNA (ceRNA ) axes that could define more reliable prognostic parameters of HGSOC, and to investigate the lncRNAs' potential mechanism of in lymphocyte infiltration.

Methods: The RNA-seq and miRNA expression profiles were downloaded from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) database; while for obtaining the differentially expressed lncRNAs (DELs), miRNAs (DEMs), and genes (DEGs), we used edgeR, limma and DESeq2. After validating the RNA, miRNA and gene expressions, using integrated three RNA expression profiles (GSE18520, GSE27651, GSE54388) and miRNA profile (GSE47841) from the Gene Expression Omnibus (GEO) database, we performed Gene Ontology (GO) and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway analyses through ClusterProfiler. The prognostic value of these genes was determined with Kaplan-Meier survival analysis and Cox regression analysis. The ceRNA network was constructed using Cytoscape. The correlation between lncRNAs in ceRNA network and immune infiltrating cells was analyzed by using Tumor IMmune Estimation Resource (TIMER), and gene markers of tumor-infiltrating immune cells were identified using Spearman's correlation after removing the influence of tumor purity.

Results: A total of 33 DELs (25 upregulated and eight downregulated), 134 DEMs (76 upregulated and 58 downregulated), and 1,612 DEGs (949 upregulated and 663 downregulated) were detected that could be positively correlated with overall survival (OS) of HGSOC. With the 1,612 analyzed genes, we constructed a ceRNA network, which indicated a pre-dominant involvement of the immune-related pathways. Furthermore, our data revealed that LINC00665 influenced the infiltration level of macrophages and dendritic cells (DCs). On the other hand, FTX and LINC00665, which may play their possible roles through the ceRNA axis, demonstrated a potential to inhibit Tregs and prevent T-cell exhaustion.

Conclusion: We defined several prognostic biomarkers for the incidence and progression of HGSOC and constructed a network for ceRNA axes; among which three were indicated to have a positive correlation with lymphocyte infiltration, namely: FTX-hsa-miR-150-5p-STK11, LINC00665-hsa-miR449b-5p-VAV3 and LINC00665-hsa-miR449b-5p-RRAGD.
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http://dx.doi.org/10.7717/peerj.8961DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7211406PMC
May 2020

miR‑508‑3p suppresses the development of ovarian carcinoma by targeting CCNA2 and MMP7.

Int J Oncol 2020 07 27;57(1):264-276. Epub 2020 Apr 27.

Department of Gynecology and Obstetrics, Tianjin Medical University General Hospital, Tianjin 300052, P.R. China.

Ovarian cancer is the most lethal gynecological tumor, and the 5‑year survival rate is only ~40%. The poor survival rate is due to cancer diagnosis at an advanced stage, when the tumor has metastasized. A better understanding of the molecular pathogenesis of tumor growth and metastasis is needed to improve patient prognosis. MicroRNAs (miRs) regulate carcinogenesis and development of cancers. However, the role of miR‑508‑3p in ovarian cancer remains largely unknown. Thus, the present study aimed to investigate the possible functions of miR‑508‑3p in the modulation of development of ovarian cancer. The results of the present study demonstrated that miR‑508‑3p mimics inhibited ovarian cancer cell proliferation, migration and invasion. Reporter gene assay results demonstrated that miR‑508‑3p suppressed cancer cell proliferation by directly targeting the 3'‑untranslated region (UTR) of cyclin A2 (CCNA2) and suppressed migration and invasion by directly targeting the 3'‑UTR of matrix metalloproteinase 7 (MMP7). In addition, high CCNA2 and MMP7 expression levels were associated with low miR‑508‑3p expression in ovarian cancer tissues. Furthermore, miR‑508‑3p and CCNA2 were independent predictors for overall survival in patients with ovarian cancer. To the best of our knowledge, this is the first study to demonstrated that miR‑508‑3p suppressed ovarian cancer development by directly targeting CCNA2 and MMP7. The results of this study suggested the potential value of miR‑508‑3p and CCNA2 as prognostic indicators and therapeutics for ovarian cancer.
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http://dx.doi.org/10.3892/ijo.2020.5055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7252466PMC
July 2020

Cyclodextrin-Modified CeO Nanoparticles as a Multifunctional Nanozyme for Combinational Therapy of Psoriasis.

Int J Nanomedicine 2020 15;15:2515-2527. Epub 2020 Apr 15.

College of Pharmacy, Weifang Medical University, Weifang, Shandong 261053, People's Republic of China.

Purpose: Reactive oxygen species (ROS)-induced oxidative stress plays a key role in the pathogenesis and progression of psoriasis by causing inflammation. Antioxidative strategies eradicating ROS may serve as effective and easy treatment options for psoriasis, while nanozymes with intrinsic antioxidant enzyme-like activity have not been explored for psoriasis treatment. The aim of this study is to fabricate β-cyclodextrins (β-CDs)-modified ceria nanoparticles (β-CDs/CeO NPs) with drug-loaded and multimimic-enzyme activities for combinational psoriasis therapy.

Methods: The β-CDs/CeO NPs were synthesized by a hydrothermal method using unmodified β-CDs as a protecting agent. The structure, size and morphology were analyzed by dynamic light scattering, transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared (FTIR) spectroscopy. Considering the superoxide dismutase (SOD)- and catalase-mimetic activities, the in vitro antioxidant activity of the β-CDs/CeO2 NPs was investigated. After dithranol (DIT) was loaded, the drug-loading capacity and release profile were determined by UV-visible light spectrophotometer and high-performance liquid chromatography. The anti-psoriatic efficacy was studied in the imiquimod (IMQ)-induced mouse model on the basis of morphological evaluation, psoriasis area and severity index calculation (PASI), and inflammatory cytokine expression.

Results: The average particle size of the blank β-CDs/CeO NPs was 60.89±0.32 nm with a polydispersity index (PDI) of 0.12, whereas that of the DIT-loaded NPs was 79.38±1.06 nm with a PDI of 0.27. TEM results showed the as-prepared NPs formed a uniform quasi-spherical shape with low polydispersity. XPS indicates synthesized NPs have a mixed Ce/Ce valence state. FTIR spectroscopy confirmed the presence of β-CDs and DIT in the NPs. Inhibition of superoxide anion rate by NPs could be reached to 79.4% in the presence of 200 µg/mL, and elimination of HO efficiency reached about 50% in the presence of 40 µg/mL, demonstrating excellent superoxide dismutase- and catalase-mimicking activities, thereby providing remarkable cryoprotection against ROS-mediated damage. Furthermore, β-CDs on the surface endowed the NPs with drug-loading function via host-guest interactions. The entrapment efficiency and drug loading of DIT are 94.7% and 3.48%, respectively. The in vitro drug release curves revealed a suitable release capability of [email protected]β-CDs/CeO NPs under physiological conditions. In IMQ-induced psoriatic model, the [email protected]β-CDs/CeO NPs exhibited excellent therapeutic effect.

Conclusion: This study may pave the way for the application of nanozyme β-CDs/CeO NPs as a powerful tool for psoriasis therapy.
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http://dx.doi.org/10.2147/IJN.S246783DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7170634PMC
July 2020

Identification of Hub Genes in High-Grade Serous Ovarian Cancer Using Weighted Gene Co-Expression Network Analysis.

Med Sci Monit 2020 Mar 17;26:e922107. Epub 2020 Mar 17.

Department of Gynecology and Obstetrics, Tianjin Medical University General Hospital, Tianjin, China (mainland).

BACKGROUND High-grade serous ovarian cancer (HGSOC) is the most malignant gynecologic tumor. This study reveals biomarkers related to HGSOC incidence and progression using the bioinformatics method. MATERIAL AND METHODS Five gene expression profiles were downloaded from GEO. Differentially-expressed genes (DEGs) in HGSOC and normal ovarian tissue samples were screened using limma and the function of DEGs was annotated by KEGG and GO analysis using clusterProfiler. A co-expression network utilizing the WGCNA package was established to define several hub genes from the key module. Furthermore, survival analysis was performed, followed by expression validation with datasets from TCGA and GTEx. Finally, we used single-gene GSEA to detect the function of prognostic hub genes. RESULTS Out of the 1874 DEGs detected from 114 HGSOC versus 49 normal tissue samples, 956 were upregulated and 919 were downregulated. The functional annotation indicated that upregulated DEGs were mostly enriched in cell cycle, whereas the downregulated DEGs were enriched in the MAPK or Ras signaling pathway. Two modules significantly associated with HGSOC were excavated through WGCNA. After survival analysis and expression validation of hub genes, we found that 2 upregulated genes (MAD2L1 and PKD2) and 3 downregulated genes (DOCK5, FANCD2 and TBRG1) were positively correlated with HGSOC prognosis. GSEA for single-hub genes revealed that MAD2L1 and PKD2 were associated with proliferation, while DOCK5, FANCD2, and TBRG1 were associated with immune response. CONCLUSIONS We found that FANCD2, PKD2, TBRG1, and DOCK5 had prognostic value and could be used as potential biomarkers for HGSOC treatment.
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http://dx.doi.org/10.12659/MSM.922107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7101203PMC
March 2020

Effect of PI3K/Akt Signaling Pathway on PRAS40Thr246 Phosphorylation in Gastric Cancer Cells.

Iran J Public Health 2019 Dec;48(12):2196-2204

Institute of Gastrointestinal Oncology, School of Medcine, Xiamen University, Xiamen, P.R. China.

Background: We aimed to investigate the effect of PI3K/Akt signaling pathway on PRAS40Thr246 phosphorylation in gastric cancer cells.

Methods: The study was conducted from April 2017 to January 2018 in Zhongshan Hospital, Xiamen University, Xiamen, China. Gastric cancer cells were divided into three groups: gastric cancer cell group, LY294002 group and MK-2206 group. Specific tests were conducted accordingly.

Results: Inhibition of PI3K/Akt signaling pathway activation and PRAS40Thr246 phosphorylation could inhibit proliferation and invasion and promote apoptosis of gastric cancer cells, and PRAS40Thr246 phosphorylation could activate PI3K/Akt signaling pathway.

Conclusion: The levels of PI3K/Akt signaling pathway related proteins and p-PRAS40Thr246 were significantly increased in gastric cancer cells. p-PRAS40-Thr246 was able to reflect the activation of the PI3K/Akt signaling pathway, reflecting the sensitivity of the PI3K/AKT signaling pathway to inhibitors.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6974862PMC
December 2019
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