Publications by authors named "Xiaotong Huang"

12 Publications

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Diagnostic Accuracy of the ADNEX Model for Ovarian Cancer at the 15% Cut-Off Value: A Systematic Review and Meta-Analysis.

Front Oncol 2021 17;11:684257. Epub 2021 Jun 17.

Department of Ultrasound, West China Second University Hospital, Sichuan University, Chengdu, China.

Objectives: To evaluate the diagnostic accuracy of the ADNEX model for ovarian cancer at the 15% cut-off value.

Methods: Studies on the identified diagnosis of the ADNEX model for ovarian cancer published in PubMed, Embase, the Cochrane Library and Web of Science databases from January 1st, 2014 to February 20th, 2021 were searched. Two researchers independently screened the retrieved studies and extracted the basic features and parameter data. The quality of the eligible studies was evaluated by Quality Assessment of Diagnostic Accuracy Studies-2, and the result was summarized by Review Manager 5.3. Meta-Disc 1.4 and STATA 16.0 were used in statistical analysis. Heterogeneity of this meta-analysis was calculated. Meta-regression was performed to investigate the potential sources of heterogeneity. Sensitivity analysis and Deek's funnel plot analysis were conducted to evaluate the stability and publication bias, respectively.

Results: 280 studies were initially retrieved through the search strategy, and 10 eligible studies were ultimately included. The random-effects model was selected for data synthesis. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio and the area under the summary receiver operating characteristic curve were 0.92 (95% CI: 0.89-0.94), 0.82 (95% CI: 0.78-0.86), 5.2 (95% CI: 4.1-6.4), 0.10 (95% CI: 0.07-0.13), 54.0 (95% CI: 37.0-77.0) and 0.95 (95% CI: 0.91-0.95). Meta-regression based on study design, country, enrollment and blind method was not statistically significant. This meta-analysis was stable with no obvious publication bias.

Conclusions: The ADNEX model at the 15% cut-off had high diagnostic accuracy in identifying ovarian cancer.
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http://dx.doi.org/10.3389/fonc.2021.684257DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8247918PMC
June 2021

Development and validation of a novel ferroptosis-related gene signature for predicting prognosis and immune microenvironment in head and neck squamous cell carcinoma.

Int Immunopharmacol 2021 Jun 12;98:107789. Epub 2021 Jun 12.

Department of Otolaryngology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China; Department of Hearing and Speech Science, Xinhua College, Sun Yat-Sen University, Guangzhou, China. Electronic address:

Ferroptosis plays an important role across variable cancer types. However, few studies have focused on the prognostic patterns of ferroptosis-related genes in HNSCC. Cohorts with mRNA expression profiles, as well as corresponding clinical data of HNSCC patients from published studies, were collected and consolidated from public databases. We performed random survival forest analysis, Kaplan-Meier (KM) analysis of best combinations, and Cox regression analysis on 231 ferroptosis-related genes to construct a gene signature in the discovery cohort (TCGA), and later validated it in the validation cohort (GEO). The 7-gene signature was constructed to stratify patients into two groups according to their level of risk. Poorer overall survival (OS) was detected in the high risk (HRisk) group than in the low risk (LRisk) group in both the TCGA cohort (P < 0.0001, HR = 1.71, 95%CI:1.41-2.07) and the GEO cohort (P < 0.001, HR = 1.68, 95%CI:1.32-2.13). The risk score was identified as an independent predictive factor of OS in multivariate Cox regression analyses (HR > 1, P < 0.0001) in both cohorts. The signature's predictive capacity was proven by the time-dependent receiver operating characteristic (ROC) curve analysis and nomogram analysis. Functional enrichment analysis revealed that immunosuppressive pathways such as matrix extracellular space, and (transforming growth factor-β)TGF-β were enriched. The HRisk group was strongly associated with upregulation of both cancer-related pathways and stromal scores, while higher proportions of anti-tumor immune cells and immune signatures were enriched in the LRisk group. In conclusion, the signature based on 7 ferroptosis-related genes could be applicable for predicting the prognosis of HNSCC, indicating that ferroptosis may be a potential therapeutic target for HNSCC.
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http://dx.doi.org/10.1016/j.intimp.2021.107789DOI Listing
June 2021

Modulation of NAD biosynthesis activates SIRT1 and resists cisplatin-induced ototoxicity.

Toxicol Lett 2021 Oct 4;349:115-123. Epub 2021 Jun 4.

Department of Otolaryngology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China; Institute of Hearing and Speech-Language Science, Sun Yat-sen University, Guangzhou, China; Department of Hearing and Speech-Language Science, Xinhua College, Guangzhou, China. Electronic address:

Cisplatin, the most widely used platinum-based anticancer drug, often causes progressive and irreversible sensorineural hearing loss in cancer patients. However, the precise mechanism underlying cisplatin-associated ototoxicity is still unclear. Nicotinamide adenine dinucleotide (NAD), a co-substrate for the sirtuin family and PARPs, has emerged as a potent therapeutic molecular target in various diseases. In our investigates, we observed that NAD level was changed in the cochlear explants of mice treated with cisplatin. Supplementation of a specific inhibitor (TES-1025) of α-amino-β-carboxymuconate-ε-semialdehyde decarboxylase (ACMSD), a rate-limiting enzyme of NADde novo synthesis pathway, promoted SIRT1 activity, increased mtDNA contents and enhanced AMPK expression, thus significantly reducing hair cells loss and deformation. The protection was blocked by EX527, a specific SIRT1 inhibitor. Meanwhile, the use of NMN, a precursor of NAD salvage synthesis pathway, had shown beneficial effect on hair cell under cisplatin administration, effectively suppressing PARP1. In vivo experiments confirmed the hair cell protection of NAD modulators in cisplatin treated mice and zebrafish. In conclusion, we demonstrated that modulation of NAD biosynthesis via the de novo synthesis pathway and the salvage synthesis pathway could both prevent ototoxicity of cisplatin. These results suggested that direct modulation of cellular NAD levels could be a promising therapeutic approach for protection of hearing from cisplatin-induced ototoxicity.
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http://dx.doi.org/10.1016/j.toxlet.2021.05.013DOI Listing
October 2021

Apoptosis inducing properties of 3-biotinylate-6-benzimidazole B-nor-cholesterol analogues.

Steroids 2021 05 12;169:108822. Epub 2021 Mar 12.

Guangxi Key Laboratory of Natural Polymer Chemistry and Physics, Key Laboratory of Beibu Gulf Environment Change and Resources Utilization, School of Chemistry and Material, Nanning Normal University, Nanning 530001, PR China. Electronic address:

In this work, a series of Biotin-substituted B-nor-cholesteryl benzimidazole compounds were synthesized. The antiproliferativeactivities of these compounds were evaluated in vitro using a series of human cancer cell lines, including HeLa (cervical cancer), SKOV3 (ovarian cancer), T-47D (thymus gland cancer), MCF-7 (human breast cancer) and HEK293T (normal renal epithelial) cells. These compounds displayed distinct antiproliferative activities against the currently tested cancer cells. The apoptotic properties induced by compound 6d were further investigated. Our results showed that compound 6d could induce the apoptosis of SKOV3 cells, blocking the cell growth in S-phase. Western blotting analyses revealed that compound 6d can induce cell apoptosis via the mitochondria-dependent pathway.
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http://dx.doi.org/10.1016/j.steroids.2021.108822DOI Listing
May 2021

Comparative study on the toxicity and removal of bisphenol S in two typical freshwater algae.

Environ Sci Pollut Res Int 2021 Jul 12;28(27):36861-36869. Epub 2021 Mar 12.

Shenzhen Key Laboratory of Environmental Chemistry and Ecological Remediation, College of Chemistry and Environmental Engineering, Shenzhen University, Shenzhen, 518060, China.

Bisphenol S (BPS), one of the most widely used bisphenol A substitutes, has recently received more attention because of its high detection in water and potential toxicity. In the present study, the toxicity and removal of BPS in typical freshwater algae Navicula sp. were investigated under laboratory conditions and the comparative study with Chlorella vulgaris was also explored. BPS was more toxic to Navicula sp. than C. vulgaris with their 120-h EC values of 3.89 and 25.19 mg/L, respectively. It may be mainly ascribed to the high tolerance of C. vulgaris to BPS. For instance, the superoxide dismutase (SOD) and catalase (CAT) activities of C. vulgaris were increased under the exposure of 20 mg BPS/L, whereas they were increased in Navicula sp. at 1 mg BPS/L. It is implied that the detoxification mechanism of C. vulgaris was activated until BPS concentration reach to 20 mg L. Moreover, the results had demonstrated that both algae had promoted the removal of BPS at 0.5 mg/L, but the removal could be inhibited as BPS concentration increased. Navicula sp. presented a better removal of BPS because of their higher accumulation, implying that they may be good materials for the removal of BPS. In addition, the sharp increase of BCF value at 72 h in Navicula sp. under the exposure of environmental-related BPS concentration (0.5 mg/L) may indicate a high risk of BPS to aquatic ecosystem. These findings will provide a reference for the risk assessment of BPS in natural waters.
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http://dx.doi.org/10.1007/s11356-021-13224-xDOI Listing
July 2021

Studies on apoptosis induced by B-norcholesteryl benzimidazole compounds in HeLa cells.

Steroids 2021 04 13;168:108802. Epub 2021 Feb 13.

Guangxi Key Laboratory of Natural Polymer Chemistry and Physics, Key Laboratory of Beibu Gulf Environment Change and Resources Utilization, School of Chemistry and Material, Nanning Normal University, Nanning 530001, PR China. Electronic address:

Certain B-norcholesteryl benzimidazole compounds were found to mediate marked anti-tumor proliferative effects in vitro in our earlier study. Here, the mechanism of action of these anti-tumor effects was evaluated using HeLa human cervical cancer cells. Methods for detecting cell invasion and migration, Annexin V-PI double staining, cell cycle status, and mitochondrial membrane potential Δψ were employed. These compounds were confirmed to significantly inhibit the proliferation of HeLa cells in vitro. Compound 1 induced apoptosis in S phase, compound 2induced apoptosis in the G/G phase and compound 3 induced late apoptosis in the G/M phase. These compounds induced HeLa cell apoptosis through depolarization of mitochondrial membrane potential Δψ in a dose-dependent manner. B-norcholesteryl benzimidazole compounds induced morphological changes in HeLa cells and inhibited proliferation, invasion and metastasis. Apoptosis was promoted by mechanisms involving p21 and p53 in this cervical cancer cell line.
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http://dx.doi.org/10.1016/j.steroids.2021.108802DOI Listing
April 2021

Untargeted metabolomics study and pro-apoptotic properties of B-norcholesteryl benzimidazole compounds in ovarian cancer SKOV3 cells.

J Steroid Biochem Mol Biol 2020 09 11;202:105709. Epub 2020 Jun 11.

Guangxi Key Laboratory of Natural Polymer Chemistry and Physics, Key Laboratory of Beibu Gulf Environment Change and Resources Utilization, School of Chemistry and Material, Nanning Normal University, Nanning 530001, PR China. Electronic address:

The current study aims to evaluate the antiproliferative activity of B-norcholesteryl benzimidazole compounds in human ovarian cancer cells (SKOV3). Our experimental data indicates that the tested compounds can induce apoptosis in SKOV3 cells, block S-phase growth, and decrease mitochondrial membrane potential. Western blot results showed that B-norcholesteryl benzimidazole compounds (1 and 2) induced apoptosis in SKOV3 cells via activation of the mitochondrial signaling pathway. Following SKOV3 cells treatment with compounds 1 and 2, the cell metabolism was assessed using the UHPLC-QE-MS (Ultra High Performance Liquid Chromatography-Q Exactive Orbitrap- Mass Spectrometry) non-target metabolomics analysis method. The results showed 10 metabolic pathways that mediated the effects of compound 1, including arginine and proline metabolism; alanine, aspartate, and glutamate metabolism; histidine metabolism; D-glutamine and D-glutamine and D-glutamate metabolism; cysteine and methionine metabolism; aminoacyl-tRNA biosynthesis; purine metabolism; Glutathione metabolism; D-Arginine and D-ornithine metabolism; and Nitrogen metabolism. From the perspective of metabolomics, compound 1 inhibits intracellular metabolism, protein synthesis, and slows down energy metabolism in SKOV3 cells. These changes result in the inhibition of proliferation and signal transduction, abrogate invasive and metastatic properties, and induce apoptosis, thus, exerting anti-tumor effects. Application of compound 2 altered activation of metabolic pathways in SKOV3 cells. The main metabolic pathways involved were glycerophospholipid metabolism; arginine and proline metabolism; purine metabolism; glycine, serine, and threonine metabolism; and ether lipid metabolism. The metabolic pathway with the greatest impact and the deepest enrichment was the glycerophospholipid metabolism. In conclusion, compound 2 inhibits proliferation of SKOV3 cells by interfering with glycerate metabolism, which plays a major role in regulation of cell membrane structure and function. Additionally, compound 2 can inhibit the invasion and metastasis of SKOV3 cells and induce apoptosis via interfering with the metabolism of arginine and proline.
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http://dx.doi.org/10.1016/j.jsbmb.2020.105709DOI Listing
September 2020

Identifying GPCR-drug interaction based on wordbook learning from sequences.

BMC Bioinformatics 2020 Apr 20;21(1):150. Epub 2020 Apr 20.

Computer Department, Jingdezhen Ceramic Institute, Jingdezhen, 333403, China.

Background: G protein-coupled receptors (GPCRs) mediate a variety of important physiological functions, are closely related to many diseases, and constitute the most important target family of modern drugs. Therefore, the research of GPCR analysis and GPCR ligand screening is the hotspot of new drug development. Accurately identifying the GPCR-drug interaction is one of the key steps for designing GPCR-targeted drugs. However, it is prohibitively expensive to experimentally ascertain the interaction of GPCR-drug pairs on a large scale. Therefore, it is of great significance to predict the interaction of GPCR-drug pairs directly from the molecular sequences. With the accumulation of known GPCR-drug interaction data, it is feasible to develop sequence-based machine learning models for query GPCR-drug pairs.

Results: In this paper, a new sequence-based method is proposed to identify GPCR-drug interactions. For GPCRs, we use a novel bag-of-words (BoW) model to extract sequence features, which can extract more pattern information from low-order to high-order and limit the feature space dimension. For drug molecules, we use discrete Fourier transform (DFT) to extract higher-order pattern information from the original molecular fingerprints. The feature vectors of two kinds of molecules are concatenated and input into a simple prediction engine distance-weighted K-nearest-neighbor (DWKNN). This basic method is easy to be enhanced through ensemble learning. Through testing on recently constructed GPCR-drug interaction datasets, it is found that the proposed methods are better than the existing sequence-based machine learning methods in generalization ability, even an unconventional method in which the prediction performance was further improved by post-processing procedure (PPP).

Conclusions: The proposed methods are effective for GPCR-drug interaction prediction, and may also be potential methods for other target-drug interaction prediction, or protein-protein interaction prediction. In addition, the new proposed feature extraction method for GPCR sequences is the modified version of the traditional BoW model and may be useful to solve problems of protein classification or attribute prediction. The source code of the proposed methods is freely available for academic research at https://github.com/wp3751/GPCR-Drug-Interaction.
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http://dx.doi.org/10.1186/s12859-020-3488-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7171867PMC
April 2020

Study on the interactions between B-norcholesteryl benzimidazole compounds with ct-DNA.

Spectrochim Acta A Mol Biomol Spectrosc 2020 Feb 31;227:117525. Epub 2019 Oct 31.

Guangxi Key Laboratory of Natural Polymer Chemistry and Physics, Key Laboratory of Beibu Gulf Environment Change and Resources Utilization, School of Chemistry and Material, Nanning Normal University, Nanning, 530001, PR China; Guangxi Colleges and University Key Laboratory of Beibu Gulf Oil and Natural Gas Resource Effective Utilization, Beibuwan University, Qinzhou, 535099, PR China. Electronic address:

The study of molecule-DNA interaction is very important for designing an improved therapeutic agent. In previous studies, we synthesized some B-norcholesteryl benzimidazole compounds, and the tests on cancer cells showed that these compounds had good in vitro anti-cancer activities. In order to further investigate mechanism of their actions, three different B-norcholesteryl benzimidazole compounds were selected and interaction of these compounds with the calf thymus DNA (ct-DNA) was monitored by using various methods including UV-Vis and fluorescence spectroscopic techniques, viscosity measurement, and circular dichroism (CD). The results proved a hypochromic effect accompanied with a slight red-shift due to the interaction of the molecules with ct-DNA. According to the UV-Vis and fluorescence spectra, the mentioned compounds were bound to DNA, preferentially through partial intercalation into the DNA helix. Moreover, the ethidium bromide (EB) and Hoechst 33258 competitive binding experiments were also used to confirm the interaction mode of the compounds with ct-DNA. In the Hoechst 33258 displacement experiment, no significant change in the fluorescence intensity was observed. Additional assays such as iodide quenching, viscosity, and CD spectroscopy further confirmed that intercalation should be the major binding mode of the selected compounds with DNA. The cytotoxicity of these three compounds was also evaluated by MTT method, and the results confirmed that binding ability of these compounds to DNA was consistent with their cytotoxicity behavior. The experimental results indicated a higher binding affinity for compound 3 compared to the other compounds. This research provided a better understanding on the molecular mechanism of the interaction between B-norcholesteryl benzimidazole compounds and tumor cells, and offered a beneficial perspective to the designation of novel B-norsteroidal anticancer compounds.
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http://dx.doi.org/10.1016/j.saa.2019.117525DOI Listing
February 2020

Predicting the Cost of Health Care Services: A Comparison of Case-mix Systems and Comorbidity Indices That Use Administrative Data.

Med Care 2020 02;58(2):114-119

Centre for Health Services and Policy Research, University of British Columbia, Vancouver.

Background: Case-mix systems and comorbidity indices aggregate clinical information about patients over time and are used to characterize need for health care services. These tools were validated for their original purpose, but those purposes are varied, and they have not been compared directly in the context of predicting costs of health care services.

Objective: To compare predictions of next-year health care service costs across 4 tools, including: the Johns Hopkins Adjusted Clinical Groups (ACG), the Elixhauser Comorbidity Index, Charlson-Deyo Comorbidity Index, and the Canadian Institute for Health Information (CIHI) population grouper.

Methods: British Columbia administrative data from fiscal years 2012-2013 were used to generate case-mix variables and the comorbidity indices. Outcome variables include next-year (2013-2014) total, physician, acute care, and pharmaceutical costs, Outcomes were modeled using 2-part models. Performance was compared using adjusted R, root mean squared error, and mean absolute error using the predicted and the actual next-year cost.

Results: Models including the CIHI grouper (239 conditions) and ACG system had similar performance in most cost categories and slightly better fit than Charlson Comorbidity Index (CCI) and Elixhauser Comorbidity Index (ECI). Adding a dummy variable for nonusers in the models for CCI and ECI increased R values slightly.

Conclusions: All these systems have empirical support for use in predicting health care costs, despite in some cases being developed for other purposes. No system is particularly effective at predicting next-year acute care cost, likely because acute events are often by definition unexpected. The freely available ECI and CCI comorbidity indices implemented using the highest-performing methods developed here may be a good choice in many circumstances.
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http://dx.doi.org/10.1097/MLR.0000000000001247DOI Listing
February 2020

Highly specific and sensitive point-of-care detection of rare circulating tumor cells in whole blood via a dual recognition strategy.

Biosens Bioelectron 2019 Oct 21;143:111604. Epub 2019 Aug 21.

Key Laboratory of Luminescent and Real-Time Analytical Chemistry, Ministry of Education, School of Chemistry and Chemical Engineering, Southwest University, Chongqing, 400715, PR China. Electronic address:

Despite the fact that the identification and detection of circulating tumor cells (CTCs) plays a critical role in cancer monitoring and diagnosis, it remains a major challenge to isolate and detect these cells, due to their extreme scarcity in peripheral blood. In this work, by coupling a dual recognition strategy and the commercial personal glucose meter, we established a point-of-care approach for detecting rare CTCs in whole blood with high sensitivity and selectivity. The antibody-conjugated magnetic beads lead to the capture and isolation of the CTCs while the enzyme- and second antibody-modified microspheres yield the signal for detection. Because of the dual recognition format, the developed method is highly selective, and a low detection limit of 7 cells can be realized as well, owing to the great signal amplification through the enzyme-loaded microbead labels. More importantly, the detection of CTCs in whole blood can be achieved in a point-of-care fashion with the using of the glucose meter transducer, offering our method a convenient and attractive alternative to traditional biopsy for the diagnosis of various cancers.
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http://dx.doi.org/10.1016/j.bios.2019.111604DOI Listing
October 2019

An enzyme-linked immunosorbent assay to compare the affinity of chemical compounds for β-amyloid peptide as a monomer.

Anal Bioanal Chem 2010 Mar 6;396(5):1745-54. Epub 2010 Feb 6.

Department of Molecular Pharmacology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu-Chong-Zhi Road, Shanghai, 201203, China.

Aβ(1-42) is the proteolytic cleavage product of cleavage of the amyloid precursor protein by β- and γ-secretases. The aggregation of Aβ(1-42) plays a causative role in the development of Alzheimer's disease. To lock Aβ(1-42) in a homogenous state, we embedded the Aβ(1-42) sequence in an unstructured region of Bcl-x(L). Both the N-terminus and the C-terminus of Aβ(1-42) were constrained in the disordered region, whereas the conjunction did not introduce any folding to Aβ(1-42) but maintained the sequence as a monomer in solution. With Bcl-x(L)-Aβ(42), we developed an enzyme-linked immunosorbent assay to compare the affinity of compounds for monomeric Aβ(1-42). Bcl-x(L)-Aβ(42) was coated on a microplate and this was followed by incubation with different concentrations of compounds. Compounds binding to Leu17-Val24 of Aβ(1-42) inhibited the interaction between Bcl-x(L)-Aβ(42) and antibody 4G8. The method can not only reproduce the activities of the reported Aβ(1-42) inhibitors such as dopamine, tannin, and morin but can also differentiate decoy compounds that do not bind to Aβ(1-42). Remarkably, using this method, we discovered a new inhibitor that binds to monomeric Aβ(1-42) and inhibits Aβ(1-42) fibril formation. As the structure of Bcl-x(L)-Aβ(42) monomer is stable in solution, the assay could be adapted for high-throughput screening with a series of antibodies that bind the different epitopes of Aβ(1-42). In addition, the monomeric form of the Aβ(1-42) sequence in Bcl-x(L)-Aβ(42) would also facilitate the identification of Aβ(1-42) binding partners by coimmunoprecipitation, cocrystallization, surface plasmon resonance technology, or the assay as described here.
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http://dx.doi.org/10.1007/s00216-009-3420-6DOI Listing
March 2010
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