Publications by authors named "Meimei Huang"

10 Publications

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ERRα inhibitor acts as a potential agonist of PPARγ to induce cell apoptosis and inhibit cell proliferation in endometrial cancer.

Aging (Albany NY) 2020 11 10;12(22):23029-23046. Epub 2020 Nov 10.

Department of Gynecology and Obstetrics, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou 350001, China.

Two transcriptional factors, peroxisome proliferator-activated receptor-γ (PPARγ) and estrogen-related receptor-α (ERRα), have been reported to be key regulators of cellular energy metabolism. However, the relationship between ERRα and PPARγ in the development of endometrial cancer (EC) is still unclear. The expression levels of PPARγ and ERRα in EC were evaluated by quantitative real-time PCR, western blot, tissue array and immunohistochemistry. A significant negative correlation was identified between PPARγ and ERRα expression in women with EC (ρ=-0.509, P<0.001). Bioinformatics analyses showed that PPARγ and ERRα can activate or inhibit the same genes involved in cell proliferation and apoptosis through a similar ModFit. ERRα activation or PPARγ inhibition could promote proliferation and inhibit apoptosis through the Bcl-2/Caspase3 pathways. Both PPARγ and ERRα can serve as serum tumor markers. Surprisingly, as evaluated by receiver operating characteristic (ROC) curves and a logistic model, a PPARγ/ERRα ratio≤1.86 (area under the ROC curve (AUC)=0.915, Youden index=0.6633, P<0.001) was an independent risk factor for endometrial carcinogenesis (OR=14.847, 95% CI= 1.6-137.748, P=0.018). EC patients with PPARγ(-)/ERRα(+) had the worst overall survival and disease-free survival rates (both P<0.001). Thus, a dynamic imbalance between PPARγ and ERRα leads to endometrial carcinogenesis and predicts the EC prognosis.
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http://dx.doi.org/10.18632/aging.104049DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7746384PMC
November 2020

Green fluorescent protein inspired fluorophores.

Adv Colloid Interface Sci 2020 Nov 13;285:102286. Epub 2020 Oct 13.

State Key Laboratory of Chemical Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, PR China.

Green fluorescence proteins (GFP) are appealing to a variety of biomedical and biotechnology applications, such as protein fusion, subcellular localizations, cell visualization, protein-protein interaction, and genetically encoded sensors. To mimic the fluorescence of GFP, various compounds, such as GFP chromophores analogs, hydrogen bond-rich proteins, and aromatic peptidyl nanostructures that preclude free rotation of the aryl-alkene bond, have been developed to adapt them for a fantastic range of applications. Herein, we firstly summarize the structure and luminescent mechanism of GFP. Based on this, the design strategy, fluorescent properties, and the advanced applications of GFP-inspired fluorophores are then carefully discussed. The diverse advantages of bioinspired fluorophores, such as biocompatibility, structural simplicity, and capacity to form a variety of functional nanostructures, endow them potential candidates as the next-generation bio-organic optical materials.
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http://dx.doi.org/10.1016/j.cis.2020.102286DOI Listing
November 2020

PGC-1α and ERRα in patients with endometrial cancer: a translational study for predicting myometrial invasion.

Aging (Albany NY) 2020 Sep 13;12(17):16963-16980. Epub 2020 Sep 13.

Laboratory of Gynecological Oncology, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou 350001, Fujian, P.R. of China.

Background: PGC-1α and ERRα are closely related to tumor formation and progression. However, the mechanism underlying the involvement of PGC-1α/ERRα in regulating invasion and migration in endometrial cancer remains to be explored.

Results: Elevated levels of PGC-1α and ERRα were associated with advanced myometrial invasion, and PGC-1α and Vimentin expression was related to the depth of myometrial invasion in premenopausal endometrial cancer. Silencing of PGC-1α reduced ERRα activation and inhibited epithelial-mesenchymal-transition phenotypes, resulting in significant inhibition of invasion and migration. Overexpression of ERRα led to enhanced PGC-1α expression and increased activity of TFEB, promoting epithelial-mesenchymal-transition in endometrial cancer cells.

Conclusions: PGC-1α and ERRα induce the epithelial-mesenchymal-transition therefore invasion and migration in endometrial cancer, and may be novel biomarkers to predict the risk of advanced myometrial invasion.

Methods: PGC-1α, ERRα, and vimentin expression was analyzed in tissue microarrays using immunohistochemistry. PGC-1α and ERRα expression in endometrial cancer cell lines was investigated using quantitative PCR and western blotting analyses after infection with lentivirus-mediated small interfering RNA (siRNA) targeting PGC-1α (siRNA-PGC-1α) or overexpressing ERRα. E-cadherin and vimentin levels were determined using western blotting and cell immunouorescence analyses. Cell migration and invasiveness were evaluated using scratch and trans-well chamber assays.
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http://dx.doi.org/10.18632/aging.103611DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7521515PMC
September 2020

Bioinspired Fluorescent Peptidyl Nanoparticles with Rainbow Colors.

ACS Appl Mater Interfaces 2020 Jul 30;12(28):31830-31841. Epub 2020 Jun 30.

State Key Laboratory of Chemical Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, P. R. China.

The growing enthusiasm to mimic the luminous properties of fluorescent proteins (FPs) has expanded to include the potential biomedical applications of FP analogues. We developed a series of non-fluorescent oligopeptides (Fc-(X); where X = F, Y, W, and H; = 1-3) that can aggregate into fluorescent nanoparticles with rainbow colors, termed the peptidyl rainbow kit (PRK). The PRK encompasses the full visible color spectrum, and its photoluminescent properties may have originated from aggregation-induced emission (AIE). Intermolecular forces restricted the intramolecular motions of the oligopeptide residues, providing a barrier to non-radiative conformational relaxation pathways and leading to AIE fluorescence. The PRK oligopeptides are pH sensitive, biocompatible, and photostable under physiological conditions, making the PRK a promising fluorescence candidate for biomedical applications.
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http://dx.doi.org/10.1021/acsami.0c08259DOI Listing
July 2020

Genome-wide DNA copy number profiling and bioinformatics analysis of ovarian cancer reveals key genes and pathways associated with distinct invasive/migratory capabilities.

Aging (Albany NY) 2020 01 2;12(1):178-192. Epub 2020 Jan 2.

Laboratory of Gynaecologic Oncology, Fujian Provincial Maternity and Children's Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou 350001, Fujian Province, China.

Ovarian cancer (OC) metastasis presents major hurdles that must be overcome to improve patient outcomes. Recent studies have demonstrated copy number variations (CNVs) frequently contribute to alterations in oncogenic drivers. The present study used a CytoScan HD Array to analyse CNVs and loss of heterozygosity (LOH) in the entire genomes of 6 OC patients and human OC cell lines to determine the genetic target events leading to the distinct invasive/migratory capacities of OC. The results showed that LOH at Xq11.1 and Xp21.1 and gains at 8q21.13 were novel, specific CNVs. Ovarian cancer-related CNVs were then screened by bioinformatics analysis. In addition, transcription factors-target gene interactions were predicted with information from PASTAA analysis. As a result, six genes (i.e., GAB2, AKT1, EGFR, COL6A3, UGT1A1 and UGT1A8) were identified as strong candidates by integrating the above data with gene expression and clinical outcome data. In the transcriptional regulatory network, 4 known cancer-related transcription factors (TFs) interacted with 6 CNV-driven genes. The protein/DNA arrays revealed 3 of these 4 TFs as potential candidate gene-related transcription factors in OC. We then demonstrated that these six genes can serve as potential biomarkers for OC. Further studies are required to elucidate the pathogenesis of OC.
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http://dx.doi.org/10.18632/aging.102608DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6977652PMC
January 2020

Epidemiology of electrical burns: a 10-year retrospective analysis of 376 cases at a burn centre in South China.

J Int Med Res 2020 Mar 19;48(3):300060519891325. Epub 2019 Dec 19.

Institute of Burn Research, State Key Laboratory of Trauma, Burn and Combined Injury, Key Laboratory of Disease Proteomics of Chongqing, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.

Objective: To investigate the epidemiological profile and associated outcomes of electrical injuries at a major burn centre in southern China.

Methods: This retrospective study enrolled consecutive electrical burn patients admitted to the burn centre of the First Affiliated Hospital of Guangxi Medical University between 2008 and 2017. Demographic and clinical data and outcomes were recorded. Mann-Whitney U tests/Pearson's chi-squared tests were used to examine the differences between low-voltage and high-voltage injuries.

Results: There were 217 high-voltage injuries and 159 low-voltage injuries. High-voltage burns were frequently observed between March and August, and low-voltage burns peaked between June and September. Burn patients were mainly men. Most burns occurred in participants aged 21 to 50 years and in industrial workers and electricians at work or householders at home. Only one person with high-voltage burns died (a mortality rate of 0.46%). Amputation rates were 37.33% for high-voltage burns and 22.01% for low-voltage burns. High-voltage injuries were associated with more extensive burns, longer hospital stays, and more complications and amputations.

Conclusions: More attention should be paid to prevention of electrical burns in male adults. Particular focus is needed on industrial workers, incidents in the spring and summer, and high-voltage injuries.
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http://dx.doi.org/10.1177/0300060519891325DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7782948PMC
March 2020

Dual targeting of estrogen receptor α and estrogen-related receptor α: a novel endocrine therapy for endometrial cancer.

Onco Targets Ther 2019 20;12:6757-6767. Epub 2019 Aug 20.

Laboratory of Gynecologic Oncology, Fujian Provincial Maternity and Children's Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou 350001, People's Republic of China.

Background: Endometrial cancer (EC) is a hormone dependent carcinoma that may involve complex molecular mechanisms. Endocrine therapy by blocking the estrogen and estrogen receptor α (ERα) has been effective in breast cancer, while it is still controversial in EC. Recently, estrogen-related receptor α (ERRα) was proven to be another endocrine therapy target.

Methods: The anti-tumor effect of selective estrogen receptor modulators (SERMs) and XCT790 (XCT) used alone or in combination were evaluated in both of ERα-positive (ERα+) and ERα-negative (ERα-) EC cells. ERα and ERRα mRNA were tested by qPCR, while the protein was detected by Western blot. The proliferation was tested by MTS and cell cycle, apoptosis rate were analyzed by flow cytometry.

Results: A relatively high dose (10 μM) of tamoxifen (TAM) suppressed the expression of ERα and ERRα in two types of EC cells. However, 10 μM raloxifene (RAL) exhibited no effect on ERα and ERRα, while 10 μM XCT down regulated ERRα specifically, but not ERα in all EC cells. When dual targeting on ERα and ERRα by combining TAM with XCT, the proliferation inhibitory effect and apoptosis reached the strongest in all EC cells (<0.05). Moreover, the inhibitory effect of proliferation was attributed significantly to the G0/G1 arrest (<0.05). Interestingly, the apoptosis induced by combining TAM with XCT were obviously higher in ERα+ EC cells than ERα- EC cells (<0.05).

Conclusion: Taken together, the results indicate that dual targeting on ERα and ERRα represents a better anti-tumor effect, which provides a novel endocrine based therapy strategy for EC.
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http://dx.doi.org/10.2147/OTT.S216146DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6709363PMC
August 2019

Clinical analysis of neoadjuvant chemotherapy in patients with advanced vulvar cancer: A STROBE-compliant article.

Medicine (Baltimore) 2018 Aug;97(34):e11786

Department of Gynecology and Obstetrics Key Laboratory of Obstetrics & Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, PR China.

To investigate the effect of neoadjuvant chemotherapy in patients with advanced vulvar cancer and to provide references for clinical treatment.Clinical and pathological data of 12 patients with advanced vulvar carcinoma were collected. The response and operability rates, adverse effects, and prognosis of neoadjuvant chemotherapy were retrospectively analyzed.The mean patient age was 45.8 (range 26-69) years. Among 12 patients, 9 underwent treatment with bleomycin and cisplatin with or without vincristine. The overall response rate was 67%. Five patients (56%) experienced grade 1 or 2 bone marrow suppression or gastrointestinal reactions. Seven patients (78%) underwent radical surgery. The mean overall survival time was 34.1 (range 3-69) months, the mean progression free survival time was 26 (range 3-69) months, and the 1-year survival rate was 83%. The other 3 patients received combined paclitaxel and cisplatin treatment. The overall response rate was 67%. All 3 patients (100%) experienced grade 2 hair loss or anemia and 2 of them (67%) underwent radical vulvectomy. The mean overall survival time was 11.7 (range 5-15) months, the mean progression free survival time was 7.7 (range 3-15) months and the 1-year survival rate was 100%. Time to overall survival and progression free survival were not significantly different between the 2 groups (P = .46 and P = .39).Owing to their high overall response rate and tolerable adverse effects, either bleomycin-cisplatin-based or paclitaxel-based neoadjuvant chemotherapy regimen can be considered a therapeutic option for advanced vulvar cancer.
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http://dx.doi.org/10.1097/MD.0000000000011786DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6113009PMC
August 2018

Novel endocrine therapeutic strategy in endometrial carcinoma targeting estrogen-related receptor α by XCT790 and siRNA.

Cancer Manag Res 2018 10;10:2521-2535. Epub 2018 Aug 10.

Department of Gynecology, Campus Virchow Clinic, Charité Medical University Berlin, Berlin, Germany.

Purpose: To explore the targeted therapy of estrogen-related receptor α (ERRα) in endometrial cancer (EC) cells and its potential mechanisms.

Methods: The mRNA and protein expression levels of ERRα and estrogen receptor α (ERα) were detected by qPCR and Western blotting in RL-952, AN3-CA, HEC-1A, and HEC-1B EC cell lines. After treatment with the ERRα-specific antagonist XCT790 or infection with lentivirus-mediated small interfering RNA (siRNA) targeting the ERRα (siRNA-ERRα), cell proliferation and apoptosis were evaluated by MTS assay and flow cytometry. After treatment with siRNA-ERRα, the expression profiles of transcription factors (TFs) were analyzed by protein/DNA arrays in EC cells.

Results: The relative mRNA levels of in RL-952 (1±0.0831) and AN3-CA (1.162±0.0325) were significantly higher than those in HEC-1A (0.3081±0.0339) and HEC-1B (0.1119±0.0091) (<0.05), and similar results were observed for ERRα protein levels. A higher ratio of was observed in ERα-positive RL-952 (10-fold) and ANC-3A (8.5-fold) cells, whereas a lower ratio was observed in ERα-negative HEC-1A (3.75-fold) and HEC-1B cells (0-fold). Both - exogenous XCT790 and endogenous siRNA-ERRα - can decrease the expression of ERRα, thereby inhibiting proliferation but promoting apoptosis in both ERα-positive and -negative EC cells. The XCT790 presented higher proliferation-inhibition and apoptosis rates in the ERα-positive than ERα-negative cells, whereas the siRNA-ERRα exhibited higher proliferation-inhibition and apoptosis rates in the ERα-negative than in ERα-positive cells. In total, 3 upregulated and 17 downregulated TFs were screened out by knocked-down expression of ERRα in all EC cells. Among them, the upregulated TFs organic cation transporter 3/4(Oct3/4), hepatic nuclear factor 4 (HNF4), HNF4 and chicken ovalbumin upstream TF (COUP-TF) as well as downregulated transcription factor EB (TFEB) were found to be statistically significant (<0.05).

Conclusion: Targeting ERRα provides a promising novel endocrine therapeutic strategy.
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http://dx.doi.org/10.2147/CMAR.S168043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6089116PMC
August 2018

Safety, pharmacokinetics, and antiviral activity of the cyclophilin inhibitor NIM811 alone or in combination with pegylated interferon in HCV-infected patients receiving 14 days of therapy.

Antiviral Res 2011 Mar 19;89(3):238-45. Epub 2011 Jan 19.

Alamo Medical Research, San Antonio, TX, USA.

Background: Cyclophilin inhibitors have shown activity against a variety of viruses, including HCV. NIM811, a novel, non-immunosuppressive cyclophilin inhibitor was studied in ascending doses in a randomized, double-blind, placebo-controlled 14-day trial in genotype 1 HCV patients. Doses of 10 up to 600 mg were given orally once or twice daily as monotherapy (9:3 randomization of NIM811:placebo). 600 mg or placebo bid for 14 days was then co-administered with pegylated interferon alpha (PEG-IFN-α) administered on days 1 and 8 to genotype 1 relapsers.

Results: NIM811 was well tolerated at all doses. Although lack of antiviral effect was noted in the monotherapy arms, liver transaminase normalization occurred at doses over 75 mg. Mild, clinically non-significant elevations of bilirubin, and significant declines in platelet numbers were observed in the 400 and 600 mg bid groups. In the combination group, the mean HCV RNA decline was 2.85 log, compared to a 0.56 log in the PEG-IFN alone arm. The mean ALT (alanine transaminase) declined significantly by day 14 in the combination, but was unchanged in the PEG-IFN alone group. In the combination therapy group, the mean platelets were 203×10(9)/L at baseline and fell to 105×10(9)/L by day 14; for patients treated with PEG-IFN the values were 177×10(9)/L and 139×10(9)/L. There was a significant increase in bilirubin, although this did not reach clinically concerning levels. There were no severe or serious adverse events. The pharmacokinetics in both monotherapy and combination arms were dose linear and not affected by PEG-INF.

Conclusion: NIM811 monotherapy resulted in a normalization of liver transaminases in the absence of significant virological response. The combination of NIM811 and pegylated interferon alpha showed significant antiviral activity compared to interferon alone in genotype 1 HCV relapsers. The use of oral cyclophilin inhibitors as part of a combination regime for treatment of hepatitis C, especially to deter resistance, holds promise.
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http://dx.doi.org/10.1016/j.antiviral.2011.01.003DOI Listing
March 2011