Publications by authors named "Xiaoqing Yi"

46 Publications

Hereditary factor V deficiency from heterozygous mutations with a novel variant p.Pro798Leufs*13 in the F5 gene.

Blood Coagul Fibrinolysis 2021 Jun 7. Epub 2021 Jun 7.

Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University Department of Clinical Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.

To explore the causative mutation for autosomal recessive inheritance factor V (FV) deficiency in a Chinese family. Relative coagulation indexes and the FV antigen were tested by the one-stage clotting method and ELISA, respectively. At the same time, the calibrated automated thrombogram (CAT) was used to analyze the mutant protein function. All 25 exons, flanking sequences, 5' and 3' untranslated regions of the F5 were amplified by PCR and sequenced directly, while each suspected variant was verified by reverse sequencing. The possible impact of the mutant was analyzed by the corresponding bioinformatics software. The phenotypic tests showed that the proband's FV activity has decreased to 24%, whereas the FV antigen has also reduced to 28%. The genetic analysis revealed that she was a compound heterozygote for a frameshift variant from small deletion in the exon 13 (c.2390_2390delC, p.Pro798Leufs*13) and a missense mutation in the exon 25 (c.6665A>G, p.Asp2222Gly). Meanwhile, the online bioinformatics software indicated that the frameshift variant was disease-causing. The pathogenic variant p.Pro798Leufs*13 and the benign variant p.Asp2222Gly largely account for the decrease of the FV deficiency in this Chinese family, of which the pathogenic variant is firstly reported in the world.
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http://dx.doi.org/10.1097/MBC.0000000000001056DOI Listing
June 2021

Biocompatible AIEgen/p-glycoprotein [email protected] paclitaxel polymeric prodrug nanoparticles for overcoming chemotherapy resistance in ovarian cancer.

Theranostics 2021 27;11(8):3710-3724. Epub 2021 Jan 27.

Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.

Nanoparticle drug delivery system (NDDS) is quite different from the widely studied traditional chemotherapy which suffers from drug resistance and side effect. NDDS offers the straightforward solution to the chemotherapy problem and provides an opportunity to monitor the drug delivery process in real time. In this vein, we developed one NDDS, namely Py-TPE/[email protected], to relieve resistance and side effects during chemotherapy against ovarian cancer. The Py-TPE/[email protected] is a multifunctional polymeric nanoparticle contained several parts as follows: (1) a nanoparticle (NP) self-assembled by reduction-sensitive paclitaxel polymeric prodrug (PMP); (2) the glutathione (GSH)-responsive release of paclitaxel (PTX) for the suppression of ovarian cancer cells; (3) the P-glycoprotein (P-gp) siRNA for restoring the sensitivity of chemo-resistant tumor cells to chemotherapy; (4) the positively charged aggregation-induced emission fluorogen (AIEgen) Py-TPE for tumor imaging and promoting encapsulation of siRNA into the nanoparticle. : The Py-TPE/[email protected] nanoparticles were prepared by self-assembly method and characterized by the UV-Vis absorption spectra, zeta potentials, TEM image, stability assay and hydrodynamic size distributions. The combinational therapeutic effects of Py-TPE/[email protected] on overcoming chemotherapy resistance were explored both and : The Py-TPE/[email protected] exhibited an average hydrodynamic size with a good stability. Meanwhile they gave rise to the remarkable chemotoxicity performances and suppressed the tumors growth in both SKOV-3/PTX (PTX resistance) subcutaneous and intraperitoneal metastasis tumor models. The investigations on ovarian cancer patient-derived xenografts (PDX) model revealed that Py-TPE/[email protected] was able to effectively overcome their chemo-resistance with minimal side effects. Our findings demonstrated the Py-TPE/[email protected] as a promising agent for the highly efficient treatment of PTX-resistant cells and overcoming the shortage of chemotherapy in ovarian cancer.
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http://dx.doi.org/10.7150/thno.53828DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7914360PMC
July 2021

Exosomes in ovarian cancer ascites promote epithelial-mesenchymal transition of ovarian cancer cells by delivery of miR-6780b-5p.

Cell Death Dis 2021 02 24;12(2):210. Epub 2021 Feb 24.

Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.

The poor prognosis of ovarian cancer is mainly due to metastasis, and the specific mechanism underlying ovarian cancer metastasis is not clear. Ascites-derived exosomes (ADEs) play an important role in the progression of ovarian cancer, but the mechanism is unknown. Here, we found that ADEs promoted ovarian cancer metastasis not only in vitro but also in vivo. This promotive function was based on epithelial-mesenchymal transition (EMT) of ovarian cancer cells. Bioinformatics analysis of RNA sequencing microarray data indicated that miR-6780b-5p may be the key microRNA (miRNA) in ADEs that facilitates cancer metastasis. Moreover, the expression of exosomal miR-6780b-5p correlated with tumor metastasis in ovarian cancer patients. miR-6780b-5p overexpression promoted and miR-6780b-5p downregulation suppressed EMT of ovarian cancer cells. These results suggest that ADEs transfer miR-6780b-5p to ovarian cancer cells, promoting EMT and finally facilitating ovarian cancer metastasis.
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http://dx.doi.org/10.1038/s41419-021-03490-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7904844PMC
February 2021

Therapeutic role of d-pinitol on experimental colitis via activating Nrf2/ARE and PPAR-γ/NF-κB signaling pathways.

Food Funct 2021 Mar 24;12(6):2554-2568. Epub 2021 Feb 24.

School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China.

Ulcerative colitis is a recrudescent intestinal inflammation coupled with diarrhea, weight loss, pus, and blood stool, which seriously impacts the quality of patient life. d-Pinitol, which can be a food supplement isolated from the food plant-like soybeans, Ceratonia siliqua Linn and Bruguiera gymnorrhiza, has been proved to show anti-oxidative and anti-inflammatory effects. However, the potential mechanism of d-pinitol still remains ill-defined contemporarily. In the current study, the therapeutic effect and potential mechanisms of d-pinitol against colitis were investigated. Oxidative stress and inflammation of experimental colitis were caused by 3% DSS treatment once daily for 7 days. During DSS treatment, the mice of the positive drug group and three other groups were orally administered SASP or d-pinitol once daily. Clinical symptoms were analyzed, and macroscopic scores were calculated. The levels of oxidative and inflammatory cytokines were measured using assay kits and RT-PCR. Additionally, the protein expression of the Nrf2/ARE pathway and PPAR-γ was measured by Western blot. Results showed that d-pinitol enormously alleviated DSS-induced bodyweight loss, colon shortening, and histological injuries, achieving a therapeutic efficacy superior to SASP. Moreover, the oxidative stress and colonic inflammatory response were mitigated. d-pinitol not only significantly activated the Nrf2/ARE signaling pathway via facilitating the translocation of Nrf2 from sitoplazma to cytoblast, upregulating the protein expression levels of GCLC, GCLM, HO-1, and NQO1, but also improved the PPAR-γ level by binding to the active site of PPAR-γ, when suppressing NF-κB p65 and IκBα phosphorylation. In conclusion, d-pinitol exhibited a dramatic anti-colitis efficacy by activating the Nrf2/ARE pathway and PPAR-γ. Hence, d-pinitol may be a promising therapeutic drug against UC in the future.
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http://dx.doi.org/10.1039/d0fo03139aDOI Listing
March 2021

GADD45B Facilitates Metastasis of Ovarian Cancer Through Epithelial-Mesenchymal Transition.

Onco Targets Ther 2021 12;14:255-269. Epub 2021 Jan 12.

Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, People's Republic of China.

Background: Growth arrest and DNA-damage-inducible 45 beta () is overexpressed and is associated with poor clinical outcomes in many human cancers, but the clinical implication of in epithelial ovarian cancer (EOC) remains unclear.

Methods: Bioinformatics analysis of The Cancer Genome Atlas (TCGA) and gene expression omnibus (GEO) cohorts was used to illustrate the relationship between expression and metastasis, as well as the survival time of EOC. was downregulated by siRNAs in EOC cells, and migration ability was determined by a transwell assay and wound-healing assay. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and gene set enrichment analysis (GSEA) were conducted to discover the downstream pathway of . The regulation of epithelial-mesenchymal transition (EMT) by GADD45B was verified by Western blotting and qRT-PCR. Finally, the correlation of expression with EOC metastasis was investigated in EOC tissues by immunohistochemistry.

Results: Overexpression of indicates shorter overall survival time and progression-free survival time, and it is an independent risk factor for poor survival in EOC patients. Elevated is related to venous invasion, lymphatic invasion and peritoneal carcinomatosis. Downregulation of GADD45B decreases the migration of ES2 and SKOV3 cells. Further KEGG enrichment analysis and GSEA revealed that EMT may be the downstream pathway of GADD45B. In addition, reduced GADD45B increases the expression of E-cadherin and decreases that of N-cadherin and vimentin. Finally, immunohistochemical analysis of GADD45B expression revealed that the expression of GADD45B in omental metastatic tissues was higher than that in matched primary ovarian cancer tissues. These results suggest that elevated GADD45B promotes the motility of ovarian cancer cells through EMT and is associated with EOC metastasis.

Conclusion: GADD45B can promote the motility of ovarian cancer cells through EMT, is associated with EOC metastasis, and may be a new biomarker of metastasis and prognosis.
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http://dx.doi.org/10.2147/OTT.S281450DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7811469PMC
January 2021

Self-Guiding Polymeric Prodrug Micelles with Two Aggregation-Induced Emission Photosensitizers for Enhanced Chemo-Photodynamic Therapy.

ACS Nano 2021 02 15;15(2):3026-3037. Epub 2021 Jan 15.

Department of Chemistry, Hong Kong Branch of Chinese National Engineering Research Center for Tissue Restoration and Reconstruction, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.

Nowadays, aggregation-induced emission luminogens (AIEgens) with reactive oxygen species (ROS) generating ability have been used as photosensitizers for imaging guided photodynamic therapy (PDT). To achieve enhanced antitumor outcomes, combining AIEgens-based PDT with chemotherapy is an efficient strategy. However, the therapeutic efficiency is hampered by the limited cellular uptake efficiency and the appropriate light irradiation occasion. In this paper, a self-guiding polymeric micelle ([email protected]) composed of two AIE photosensitizers and a reduction-sensitive paclitaxel prodrug (PTX-SS-N) was established for enhanced chemo-photodynamic therapy by a dual-stage light irradiation strategy. When the micelles were accumulated in tumor tissues, the first light irradiation (L, 6 min) was utilized to facilitate cellular uptake by "photochemical internalization" (PCI). Then, the intracellular glutathione (GSH) would induce the PTX release, micelles disassembly and the aggregation state change of AIEgens. The fluorescence signal change of two AIEgens-based ratiometric fluorescent probe could not only precisely guide the second light irradiation (L, 18 min) for sufficient ROS production, but also monitor the nonfluorescent drug PTX release in turn. Both and studies demonstrated that the dual-stage light irradiation strategy employed for [email protected] micelles exhibited a superior therapeutic effect over only 24 min continuous light irradiation.
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http://dx.doi.org/10.1021/acsnano.0c09407DOI Listing
February 2021

EZH2 activates CHK1 signaling to promote ovarian cancer chemoresistance by maintaining the properties of cancer stem cells.

Theranostics 2021 1;11(4):1795-1813. Epub 2021 Jan 1.

Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.

Ovarian cancer is a fatal malignant gynecological tumor. Ovarian cancer stem cells (OCSCs) contribute to resistance to chemotherapy. The polycomb group protein enhancer of zeste homolog 2 (EZH2) plays a key role in maintaining CSCs. Here, we aimed to investigate the specific mechanism by which EZH2 regulates CSCs to result in chemoresistance and poor prognosis of ovarian cancer. We used a nude mouse model to obtain a cell line enriched for OCSCs, named SK-3rd cells. The CRISPR and Cas9 endonuclease system was used to establish an EZH2-knockout SK-3rd ovarian cancer cell line. High-throughput PCR array and bioinformatics methods were used to screen the EZH2 target involved in CSC stemness. A luciferase reporter assay and chromatin immunoprecipitation assay were performed to identify activation of CHK1 by EZH2. We evaluated associations between EZH2/CHK1 expression and the chemoresistance and prognosis of ovarian cancer patients. EZH2 plays a critical role in maintaining ovarian CSC stemness and chemo-resistance. CHK1 is an EZH2 target involved in CSC stemness. Knockdown of EZH2 in ovarian CSCs decreased CHK1 expression, while CHK1 overexpression was sufficient to reverse the inhibitory effect on spheroid formation and chemoresistance caused by repression of EZH2. In addition, EZH2 was also shown to play a unique role in activating rather than repressing CHK1 signaling through binding to the CHK1 promoter in epithelial ovarian cancer cells. Finally, in clinical samples, ovarian cancer patients with high levels of EZH2 and CHK1 not only were more resistant to platinum but also had a poorer prognosis. Our data revealed a previously unidentified functional and mechanistic link between EZH2 levels, CHK1 signaling activation, and ovarian CSCs and provided strong evidence that EZH2 promotes ovarian cancer chemoresistance and recurrence.
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http://dx.doi.org/10.7150/thno.48101DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7778604PMC
August 2021

A Novel Nanosystem Realizing Curcumin Delivery Based on [email protected] Dots Nanocomposite for Alzheimer's Disease Therapy.

Front Bioeng Biotechnol 2020 3;8:614906. Epub 2020 Dec 3.

Oil-tea in Medical Health Care and Functional Product Development Engineering Research Center in Jiangxi, Key Laboratory of Biomaterials and Biofabrication in Tissue Engineering of Jiangxi Province, Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases, Ministry of Education, Gannan Medical University, Ganzhou, China.

Alzheimer's disease (AD) is the most common neurodegenerative disease, which seriously affects human health but lacks effective treatment methods. Amyloid β (Aβ) aggregates are considered a possible target for AD treatment. Evidence is increasingly showing that curcumin (CUR) can partly protect cells from Aβ-mediated neurotoxicity by inhibiting Aβ aggregation. However, the efficiency of targeted cellular uptake and bioavailability of CUR is very low due to its poor stability and water-solubility. In order to better improve the cell uptake efficiency and bioavailability of CUR and reduce the cytotoxicity of high-dose CUR, a novel CUR delivery system for AD therapy has been constructed based on the employment of the [email protected] dots nanocomposite ([email protected]) as the carrier. [email protected] have a strong affinity toward Aβ and effectively inhibit extracellular Aβ fibrillation. In addition, [email protected] can inhibit the production of reactive oxygen species (ROS) mediated by Aβ fibrils and the corresponding neurotoxicity in PC12 cells. More importantly, it can restore nerve damage and maintained neuronal morphology. These results indicate that the application of [email protected] provides a promising platform for the treatment of AD.
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http://dx.doi.org/10.3389/fbioe.2020.614906DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7744485PMC
December 2020

Recent advance in biosensing applications based on two-dimensional transition metal oxide nanomaterials.

Talanta 2020 Nov 29;219:121308. Epub 2020 Jun 29.

School of Materials and Chemical Engineering, Zhongyuan University of Technology, Zhengzhou, 450007, China. Electronic address:

In recent years, two-dimensional transition metal oxide nanomaterials (2D TMONs) have drawn increasing attention due to their various functionalization, tunable electronic characteristics, unique optical properties, excellent chemical and thermal stabilities, large surface area and strong oxidation ability. The metal ions of 2D TMONs usually possessed the unfilled d-orbital. Furthermore, 2D TMONs contained oxygen ion in comparison with other 2D nanomaterials. Thus, 2D TMONs has a series of features which included reactive electronic transitions, high dielectric constants, wide bandgaps and excellent electrical property. They could act as quencher to quench the fluorescence intensity of fluorescent sensor or electrochemiluminescence. Recently, they have been demonstrated both excellent biological compatibility and good dispersion for the oxygen ions. These properties endow 2D TMONs could be used in optic, electronic, catalytic, energy technology, biosensing to biomedical diagnosis and therapy. In this review, we provide a brief overview regarding the progress of 2D TMONs based biosensors that function through various analytical methods including fluorescence, chemiluminescence, electrochemical and colorimetric in recent five years. The review may do some help to the researchers who are interested in 2D TMONs based biosensors.
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http://dx.doi.org/10.1016/j.talanta.2020.121308DOI Listing
November 2020

Photoresponsive Electrochemical DNA Biosensors Achieving Various Dynamic Ranges by Using Only-One Capture Probe.

Anal Chem 2020 07 9;92(14):9963-9970. Epub 2020 Jul 9.

Engineering Research Center of Nano-Geomaterials of Ministry of Education, Faculty of Materials Science and Chemistry, China University of Geosciences, Wuhan 430074, China.

The rational design of DNA capture probes for modulating the binding affinity to tune the dynamic range of electrochemical DNA (E-DNA) biosensors is valuable and effective. Most of current strategies, however, require designing several DNA capture probes to achieve the tunable dynamic range, which is cumbersome and costly. Herein, we develop the photoresponsive E-DNA biosensors with tunable dynamic ranges by using only one photocleavable capture probe (PC-CP). The photoresponsive PC-CP is a stem-loop DNA structure containing a photocleavable linker (PC-linker) in the loop. The PC-linker can be cleaved by UV irradiation to switch the structure of PC-CP, through which the binding affinity to the target could be tuned. In this way, the dynamic range, the sensitivity, and the specificity of photoresponsive E-DNA biosensors can be tuned. Furthermore, the developed photoresponsive E-DNA biosensors enable sensitive and selective detection of target DNA in complex samples with a tunable dynamic range, which offers the possibility of clinical applications.
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http://dx.doi.org/10.1021/acs.analchem.0c01571DOI Listing
July 2020

Mechanisms of impaired pancreatic β‑cell function in high‑fat diet‑induced obese mice: The role of endoplasmic reticulum stress.

Mol Med Rep 2020 May 5;21(5):2041-2050. Epub 2020 Mar 5.

Department of Pediatrics, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.

The aim of the study was to examine whether there was excessive endoplasmic reticulum stress (ERs) in the islets of high‑fat diet (HFD)‑induced obese mice, as well as the effects of ERs on β‑cell function. Male C57BL/6J mice were fed a HFD for 16 weeks. Pancreatic β‑cell function was evaluated using intraperitoneal glucose tolerance and insulin release tests, and via electron microscopy. The expression of activating transcription factor 6 (ATF6) and phosphorylated (p)‑eukaryotic initiation factor 2α (eIF2α) were detected via immunofluorescence staining to determine whether exposure to a HFD induced ERs in pancreatic islets. In vitro, ERs was induced by palmitate (PA) in INS‑1 cells, and the protein expression of ATF6, and mRNA expression of ATF6 and insulin were examined via western blot and quantitative PCR (qPCR) analyses, respectively. The nuclear localization of ATF6 was examined by immunofluorescence. Finally, small interfering (si)RNA was used to downregulate ATF6 expression in INS‑1 cells to further determine whether ATF6 mediated the ERs‑induced impairment of insulin gene transcription. After 16 weeks of induction, the obese mice showed impaired glucose tolerance, insulin resistance and hyperinsulinemia. Immunohistochemistry staining showed increased p‑eIF2α and ATF6 expression in pancreatic islets in the obesity group compared with the normal group. Electron microscopy indicated that the microstructures and secretory functions of β‑cells were impaired. After 24 h of incubation, ATF mRNA and protein expression in the PA group was significantly higher compared with the control group. However, the insulin mRNA expression in the PA group was significantly decreased. Furthermore, qPCR showed that the insulin mRNA expression was significantly increased 24 h after PA treatment in cells transfected with ATF6‑siRNA compared with the negative control group. The present suggested shows that ERs‑induced activation of ATF6 may play an important role in the development of β‑cell dysfunction in obese mice.
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http://dx.doi.org/10.3892/mmr.2020.11013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7115219PMC
May 2020

Protective Effect of (L.) Lam. Fruit on Dextran Sulfate Sodium-Induced Ulcerative Colitis in Mice: Role of Keap1/Nrf2 Pathway and Gut Microbiota.

Front Pharmacol 2019 3;10:1602. Epub 2020 Feb 3.

Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China.

(BG), a medicinal mangrove, and its fruit (a food material) (BGF), have traditionally been used to treat diarrhea (also known as ulcerative colitis) in folk medicine. However, the mechanism of action against colitis remains ambiguous. This study aimed to investigate the potential efficacy and mechanism of BGF on experimental colitis. Colitis was induced by oral intake of dextran sulfate sodium (DSS) and treated with aqueous extract of BGF (25, 50 and 100 mg/kg) for a week. The Disease Activity Index (DAI), colon length, and histological changes of colon were analyzed. The inflammatory and oxidative stress status was explored. The protein expression of Nrf2 and Keap1 in the colon was detected by Western blotting. The mRNA expression of Nrf2 downstream genes (, , and ) was determined by RT-PCR. Furthermore, the effect on intestinal flora was analyzed. Results indicated that BGF was rich in pinitol, and showed strong antioxidative activity . Compared with the DSS model, BGF effectively reduced the body weight loss and DAI, restored the colon length, repaired colonic pathological variations, and decreased the histological scores, which was superior to salicylazosulfapyridine (SASP) with smaller dosage. Moreover, BGF not only abated the levels of MDA and inflammatory mediators (TNF-α, IL-6, IL-1β, and IFN-γ), increased the level of IL-10, but also prevented the depletion of SOD and GSH. BGF upregulated the protein level of nuclear Nrf2 and mRNA levels of , , and , while significantly inhibited the protein expression of Keap1 and cytosolic Nrf2. Besides, BGF promoted the growth of probiotics (, , and ) in the gut, and inhibited the colonization of pathogenic bacteria ( and ), which contributed to the maintenance of intestinal homeostasis. BGF possessed protective effect against DSS-induced colitis. The potential mechanism of BGF may involve the amelioration of inflammatory and oxidative status, activation of Keap1/Nrf2 signaling pathway, and maintenance of micro-ecological balance of the host. This study provides experimental evidence for the traditional application of BGF in the treatment of diarrhea, and indicates that BGF may be a promising candidate against colitis.
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http://dx.doi.org/10.3389/fphar.2019.01602DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7008401PMC
February 2020

Knockdown of CTRP6 inhibits high glucose-induced oxidative stress, inflammation and extracellular matrix accumulation in mesangial cells through regulating the Akt/NF-κB pathway.

Clin Exp Pharmacol Physiol 2020 07 16;47(7):1203-1211. Epub 2020 Mar 16.

Department of Pediatrics, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

C1qTNF-related protein 6 (CTRP6) is a member of the CTRP family and exerts a key role in the progression of diabetes mellitus. However, the role of CTRP6 in diabetic nephropathy remains unknown. The present study was designed to examine the roles of CTRP6 in diabetic nephropathy and explore the potential molecular mechanisms. Our results showed that the expression level of CTRP6 was significantly increased in high glucose (HG)-stimulated glomerular mesangial cells (MCs). The following loss/gain-of-function assays demonstrated that CTRP6 knockdown significantly inhibited HG-induced reactive oxygen species (ROS) production in MCs. CTRP6 knockdown caused significant decreases in tumour necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-6 production levels in HG-induced MCs. Moreover, knockdown of CTRP6 inhibited HG-stimulated extracellular matrix (ECM) accumulation in MCs characterized by decreased expression and production levels of fibronectin (FN) and collagen IV (Col IV). Furthermore, CTRP6 knockdown suppressed HG-induced the activation of Akt/NF-κB pathway in MCs, while overexpression of CTRP6 exhibited the opposite effects. Treatment with LY294002, an inhibitor of Akt, reversed the induction effects of CTRP6 overexpression on ROS production, inflammation and ECM accumulation in MCs. In conclusion, these findings demonstrated that CTRP6 knockdown inhibits HG-induced ROS production, inflammation and ECM accumulation in MCs, which were mediated by the inactivation of the Akt/NF-κB pathway. The roles of CTRP6 in diabetic nephropathy provided evidence for its therapeutic potential for the treatment of diabetic nephropathy.
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http://dx.doi.org/10.1111/1440-1681.13289DOI Listing
July 2020

Disordered cutaneous microbiota in systemic lupus erythematosus.

J Autoimmun 2020 03 26;108:102391. Epub 2019 Dec 26.

Department of Dermatology, Hunan Key Laboratory of Medical Epigenomics, The Second Xiangya Hospital of Central South University, Changsha, China; Research Unit of Key Technologies of Immune-related Skin Diseases Diagnosis and Treatment, Chinese Academy of Medical Sciences (2019RU027), Changsha, China. Electronic address:

The correlation between systemic lupus erythematosus (SLE) and microbiota colonization has been receiving much attention during recent years. Here, we screened the cutaneous bacterial spectrums of 69 SLE patients, 49 healthy controls and 20 dermatomyositis (DM) patients and identified the specific changes of cutaneous microbial composition and abundance in SLE patients. We observed the decreasing diversity in community richness and evenness and the greater heterogeneity in SLE patients compared to healthy controls, which were also different from the cutaneous microbiome of DM patients. The skin microbial community disorders in SLE patients were correlated with several clinical features such as serum low complement level, gender, renal involvement and myositis. According to the Kruskal-Wallis (KW) test, receiver operating characteristic (ROC) curve and LDA Effect Size (LEfSe) analysis, several bacterial taxa such as Staphylococcus, especially Staphylococcus aureus and Staphylococcus epidermidis, were identified to be potential markers for SLE skin lesions. Furthermore, Picrust analysis showed that Staphylococcus aureus infection pathway was significantly enriched and exhibited a strong correlation with genus Staphylococcus in SLE patients. The changes in the composition and abundance of cutaneous microbiota in SLE patients suggest that the microbial dysbiosis is associated with the pathogenesis of SLE, which may be potentially reliable biomarker or therapeutic target for SLE.
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http://dx.doi.org/10.1016/j.jaut.2019.102391DOI Listing
March 2020

Serum Asprosin Concentrations Are Increased and Associated with Insulin Resistance in Children with Obesity.

Ann Nutr Metab 2019 27;75(4):205-212. Epub 2019 Nov 27.

Department of Pediatrics, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China,

Objective: Asprosin, a novel peptide that has recently discovered as an important regulatory adipokine, is relevant to obesity in animals and adult humans. Little is known about its roles in children. The aim of the current study was to determine the potential role of asprosin and explore its relationship to various obesity-related markers in children with obesity.

Methods: A cross-sectional study was conducted among 119 Chinese children, including 79 children with obesity and 40 lean controls. Anthropometric parameters, clinical data, and circulating tumor necrosis factor-α (TNF-α), adiponectin, leptin, and asprosin levels were measured.

Results: Serum asprosin concentrations were significantly elevated in children with obesity compared with lean controls. Children with insulin resistance (IR) had higher asprosin levels than non-IR group. Asprosin was positively correlated with waist-to-hip ratio (WHR), diastolic blood pressure, homoeostasis model of IR (HOMA-IR), leptin-to-adiponectin ratio, TNF-α independent of their body mass index, SDs score, and age. In multivariable linear regression analysis, WHR and HOMA-IR were associated with the circulating level of asprosin.

Conclusions: Circulating asprosins are increased in children with obesity and associated with IR. It may be proposed as a novel marker to predict advanced disease.
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http://dx.doi.org/10.1159/000503808DOI Listing
September 2020

Drug delivery micelles with efficient near-infrared photosensitizer for combined image-guided photodynamic therapy and chemotherapy of drug-resistant cancer.

Biomaterials 2019 10 2;218:119330. Epub 2019 Jul 2.

State Key Laboratory of Luminescent Materials and Devices, Center for Aggregation-Induced Emission, South China University of Technology, Guangzhou, 510640, China; Department of Chemistry, Hong Kong Branch of Chinese National Engineering Research Center for Tissue Restoration and Reconstruction, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China. Electronic address:

The combination of photodynamic therapy (PDT) and chemotherapy (CT) offers a promising approach for the tumor eradication for overcoming multidrug resistance (MDR), which is a major obstacle to effective cancer treatment. However, for PDT, simultaneously achieving near-infrared (NIR) emission and efficient reactive oxygen species (ROS) generation with low dark toxicity is urgently needed but remains challenging. Herein, a series of novel fluorophores with strong NIR emission, hybridized local and charge transfer characteristics, good two-photon absorption, high photostability, low dark cytotoxicity and excellent ROS generation ability are developed. By encapsulating the NIR fluorophore (DEB-BDTO) as a photosensitizer along with a drug resistance inhibitor tariquidar (TQR) within a polymeric prodrug (PMP), a reduction-sensitive drug co-delivery system (DEB/[email protected] micelles) is constructed. The DEB/[email protected] micelles exhibit a prominent synergistic lethal effect of PDT and CT on SKOV-3 cells and SKOV-3/MDR cells, and can apparently enhance the inhibition of tumor growth compared with sole PDT or CT in the tumor-bearing mouse model. Both in vitro and in vivo experiments prove that the new NIR fluorophores are excellent photosensitizers and can furnish an efficient combination therapy of image-guided PDT and CT within drug delivery micelles, which is particularly useful for eradicating multidrug resistance cancer.
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http://dx.doi.org/10.1016/j.biomaterials.2019.119330DOI Listing
October 2019

Evaluation of the Relationship Between Common Variants in the Gene and Hip Osteoarthritis Susceptibility.

Genet Test Mol Biomarkers 2019 Jun 8;23(6):373-379. Epub 2019 May 8.

2 Department of Orthopaedic Surgery, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

Hip osteoarthritis (HOA) is one of the most common types of osteoarthritis and affects nearly 10% of men and 18% of women who are >60 years of age worldwide. It has been demonstrated to be a genetic disease with a 50% heritability risk. Recently, the gene has been associated with knee OA in both Turkish and Chinese populations, but the relationship between the gene and HOA has not been evaluated. In this study, we aimed to evaluate the relationship between the common genetic variants in the gene and the predisposition of Han Chinese individuals to HOA. A total of 730 HOA patients and 1220 healthy controls were recruited in a hospital-based case-control study. Six common single nucleotide polymorphisms (SNPs) of the gene were selected for genotyping, and genetic association analyses were performed using both single-marker and haplotype-based methods. The SNP rs187084 was found to be significantly associated with the risk of HOA after a Bonferroni correction (adjusted allelic -values with age, gender, and body mass index [BMI] = 0.0008). The results indicated that the A allele of rs187084 is a risk allele for HOA and is likely to be a predisposing factor leading to an increased risk of HOA (adjusted odds ratio with age, gender, and BMI = 1.26, 95% confidence interval = 1.10-1.43). The results of the haplotype analyses confirmed a similar pattern to the SNP analyses. Our study provides strong evidence that variations in the gene are closely linked with genetic susceptibility to HOA in the Han Chinese population. This finding furthers the role of TLR-9 in the development and occurrence of OA in general.
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http://dx.doi.org/10.1089/gtmb.2019.0010DOI Listing
June 2019

TNF-α Upregulates IKKε Expression via the Lin28B/let-7a Pathway to Induce Catecholamine Resistance in Adipocytes.

Obesity (Silver Spring) 2019 05 1;27(5):767-776. Epub 2019 Apr 1.

Department of Pediatrics, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an Shaanxi, People's Republic of China.

Objective: Overexpression of inhibitor of nuclear factor kappa-B kinase subunit epsilon (IKKε) contributes to blunted catecholamine-induced lipolysis. Tumor necrosis factor α (TNF-α) upregulates adipose IKKε expression to inhibit stimulated lipolysis, which can be reversed by IKKε inhibitors. This study investigated adipose IKKε expression in children with and without obesity and potential involvement of the Lin28B/let-7a axis in posttranscriptional regulation of TNF-α-stimulated IKKε in adipocytes.

Methods: Adipose IKKε was detected in children both with and without obesity. The effects of TNF-α on IKKε expression of adipocytes were investigated. Inhibitor and mimics of microRNA let-7a or short interfering RNA of protein lin-28 homolog B (Lin28B) were used to determine the effect of the Lin28B/let-7a axis on TNF-α-mediated IKKε upregulation. Reporter assays were performed to confirm that let-7a targets the IKKε gene.

Results: Adipose IKKε expression in children with obesity was upregulated to a greater extent than that in children without obesity and was positively correlated with BMI. TNF-α increased IKKε expression through activation of Lin28B/let-7a and then inhibited isoproterenol-stimulated lipolysis in adipocytes. Blocking the Lin28B /let-7a axis rescued inhibition of isoproterenol-stimulated lipolysis produced by TNF-α by inhibiting IKKε expression. Reporter assays confirmed that IKKε is a target of let-7a.

Conclusions: Adipose IKKε expression in children with obesity is substantially elevated and positively correlated with BMI. TNF-α induces catecholamine resistance via activation of the Lin28B/let-7a/IKKε pathway.
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http://dx.doi.org/10.1002/oby.22434DOI Listing
May 2019

Preclinical evaluation of a novel anterior non-fusion fixation device for atlantoaxial instability: an in vivo comparison study in a canine model.

Eur Spine J 2019 05 13;28(5):1225-1233. Epub 2019 Feb 13.

Department of Orthopaedic Surgery, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, People's Republic of China.

Purpose: The Anterior Atlantoaxial Non-Fusion Fixation System (AANFS) was a novel motion preservation device for atlantoaxial instability to replace traditional fusion techniques. The purpose of this in vivo study was to evaluate the clinical features and biomechanical properties of this new device in a canine model by comparing it with a conventional method.

Methods: Eighteen adult male canines were randomly divided into group 1, which received the AANFS replacement, group 2 which received the Harms rigid fixation procedures, and group 3, which served as the control group. Routine follow-up evaluations were performed postoperatively. Specimens were harvested 12 weeks after the operation. Biomechanical tests were conducted to obtain the range of motion (ROM) and neutral zone (NZ) at C1-C2 segment in different groups.

Results: The canines successfully tolerated the entire experimental procedure. No significant differences were found in surgery time, blood loss and recovery time between the AANFS group and the Harms rigid fixation group. Radiological examinations revealed that the position of the implant was good. Biomechanical results showed that, compared with the intact group, the mean ROM and NZ in flexion, extension, lateral bending and rotation were significantly reduced after rigid fixation. However, after the AANFS implantation, ROM and NZ in all directions were similar to those of the intact state.

Conclusions: This study for the first time provides an animal model for studying non-fusion strategies of upper cervical spine. The AANFS was able to maintain movement function of the atlantoaxial joint and may be an alternative to traditional fusion techniques. These slides can be retrieved under Electronic Supplementary Material.
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http://dx.doi.org/10.1007/s00586-019-05916-3DOI Listing
May 2019

Photoactivated Nanoflares for mRNA Detection in Single Living Cells.

Anal Chem 2019 02 28;91(3):2021-2027. Epub 2019 Jan 28.

Engineering Research Center of Nano-Geomaterials of Ministry of Education, Faculty of Materials Science and Chemistry , China University of Geosciences , Wuhan 430074 , China.

Gold nanoparticles (AuNPs) have shown great promise as a universal platform for biosensing and are often functionalized with a densely packed DNA for intracellular detection. While DNA-AuNP conjugates, such as nanoflares, have been used for single and multiple mRNA molecules detection in living cells, the target recognition reaction is triggered once they enter into cells, making it impossible to control the initial reaction at the desired time. To solve this problem, we have designed photoactivated (PA) nanoflares for intracellular mRNA analysis with high spatiotemporal control. PA nanoflares consist of AuNP and photoresponsive DNA hairpin probes. Without UV irradiation, the DNA hairpin could be kept unawakened and show no reactivity to target the probe. Upon UV activation, the hairpin structures are destroyed and expose the sticky domains, which act as toeholds to mediate strand displacement reactions, making flares release from the gold surface and causing an increase of fluorescence. By tuning light irradiation, PA nanoflares for mRNA detection in living cells can be temporally controlled. With the benefit from two-photon laser illumination, PA nanoflares can detect mRNA in selective cells at a desired time point at the single-cell level. Compared to the traditional nanoflares, the novel PA nanoflares have increased the detection sensitivity and achieved intracellular biomarkers detection at the single-cell level with high spatiotemporal control.
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http://dx.doi.org/10.1021/acs.analchem.8b04434DOI Listing
February 2019

A high therapeutic efficacy of polymeric prodrug nano-assembly for a combination of photodynamic therapy and chemotherapy.

Commun Biol 2018 21;1:202. Epub 2018 Nov 21.

Engineering Research Center of Nano-Geomaterials of Ministry of Education, Faculty of Materials Science and Chemistry, China University of Geosciences, Wuhan, 430074, China.

Combination of photodynamic therapy and chemotherapy has been emerging as a new strategy for cancer treatment. Conventional photosensitizer tends to aggregate in aqueous media, which causes fluorescence quenching, reduces reactive oxygen species (ROS) production, and limits its clinical application to photodynamic therapy. Traditional nanoparticle drug delivery system for chemotherapy also has its disadvantages, such as low drug loading content, drug leakage, and off-target toxicity for normal tissues. Here, we developed a reduction-sensitive co-delivery micelles [email protected] for combinational therapy, which composed of entrapping a red aggregation-induced emission fluorogen (AIEgen) for photodynamic therapy and PMP that contains a reduction-sensitive paclitaxel polymeric prodrug for chemotherapy. AIEgen photosensitizer illustrates a much improved photostability and ROS production efficiency in aggregate state and PMP loads a high dose of paclitaxel and carries a smart stimuli-triggered drug release property. This co-delivery system provides a better option that replaces AIEgen photosensitizer for cancer diagnosis and therapy.
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http://dx.doi.org/10.1038/s42003-018-0204-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6249255PMC
November 2018

In-situ synthesis of amorphous HTiO-modified TiO and its improved photocatalytic H-evolution performance.

J Colloid Interface Sci 2018 Dec 31;532:272-279. Epub 2018 Jul 31.

State Key Laboratory of Advanced Technology for Material Synthesis and Processing, Wuhan University of Technology, Wuhan 430070, People's Republic of China.

Surface cocatalyst modification is considered as one of the most ideal strategies for improved photocatalytic H-evolution activity of photocatalysts. It is quite important to develop new cocatalyst and to enhance the interfacial coupling between cocatalysts and photocatalysts with the aim of promoting the rapid transfer of photogenerated charge. In this work, amorphous HTiO (a-HTiO) nanoparticles (ca. 1 nm), as a novel and effective hole cocatalyst, were homogeneously in-situ generated on TiO surface (the sample was referred as a-HTiO/TiO) via a first controllable surface reaction of TiO in a NaOH solution and the following ion-exchange reaction with HCl solution at room temperature. The resultant a-HTiO/TiO photocatalysts exhibited greatly enhanced photocatalytic H-evolution performance compared with pure TiO, which was mainly attributed to amorphous HTiO nanoparticles as hole cocatalysts for rapid hole transfer. To further promote the photocatalytic activity of a-HTiO/TiO, Ni(OH) as electron cocatalysts was loaded on the surface of a-HTiO/TiO to prepare the co-modified a-HTiO/TiO/Ni(OH) photocatalyst. The results indicated that the H-evolution performance of the a-HTiO/TiO/Ni(OH) photocatalyst was significantly higher than that of a-HTiO/TiO by a factor of 66.7 due to the synergy of a-HTiO and Ni(OH) cocatalysts. This study provides a strategic approach for enhanced H-evolution activity by enhanced interfacial coupling between cocatalysts and photocatalysts.
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http://dx.doi.org/10.1016/j.jcis.2018.07.139DOI Listing
December 2018

DNA-Conjugated Amphiphilic Aggregation-Induced Emission Probe for Cancer Tissue Imaging and Prognosis Analysis.

Anal Chem 2018 07 21;90(13):8162-8169. Epub 2018 Jun 21.

Hubei Key Laboratory of Bioinorganic Chemistry & Materia Medica, School of Chemistry and Chemical Engineering, Department of Obstetrics and Gynecology, Tongji Hospital Tongji Medical College , Institute of Pathology of Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology , Wuhan 430074 , P. R. China.

Detection of an ultralow concentration of mRNA is important in the prognosis of gene-related diseases. In this study, a DNA-conjugated amphiphilic aggregation-induced emission probe (TPE-R-DNA) was synthesized for cancer tissue imaging and prognosis analysis based on an exonuclease III-aided target recycling technique. TPE-R-DNA comprise two components: a hydrophobic component that serves as the "turn-on" long wavelength fluorescence imaging agent (TPE-R-N); and a hydrophilic single DNA strand (Alk-DNA) which acts as specific recognition part for target mRNA. In the absence of target mRNA, TPE-R-DNA had almost no fluorescence because of its high water solubility. Conversely, the TPE-R-DNA was digested by exonuclease III (Exo III) in the presence of MnSOD mRNA to release the hydrophobic fluorogens (TPE-R-AT). Subsequently, TPE-R-AT formed aggregates, and therefore, fluorescence signal was distinctly observed. For the first time, the structure of the hydrolysis product (TPE-R-AT), containing two bases A and T, was proved by the mass spectrum (MS) and high-performance liquid chromatography (HPLC). Moreover, the detection limit toward mRNA could be achieved in as low as 0.6 pM. Furthermore, the fluorescent signal can be used to confirm the MnSOD mRNA expression level in cancer tissue. The MnSOD mRNA expression in renal cancer was lower than in renal cancer adjacent tissue. In particular, the expression level was analyzed to predict prognosis of cancer patients. Our results demonstrate that a shorter survival time was evident among patients in lower MnSOD mRNA expression. Thereby, it indicates great potential for the development of an ultrasensitive biosensing platform for the application in disease prognosis.
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http://dx.doi.org/10.1021/acs.analchem.8b01456DOI Listing
July 2018

Integrated analysis of long noncoding RNA and mRNA expression profile in children with obesity by microarray analysis.

Sci Rep 2018 06 8;8(1):8750. Epub 2018 Jun 8.

Department of Pediatrics, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, People's Republic of China.

Long noncoding RNAs (lncRNAs) have an important role in adipose tissue function and energy metabolism homeostasis, and abnormalities may lead to obesity. To investigate whether lncRNAs are involved in childhood obesity, we investigated the differential expression profile of lncRNAs in obese children compared with non-obese children. A total number of 1268 differentially expressed lncRNAs and 1085 differentially expressed mRNAs were identified. Gene Ontology (GO) and pathway analysis revealed that these lncRNAs were involved in varied biological processes, including the inflammatory response, lipid metabolic process, osteoclast differentiation and fatty acid metabolism. In addition, the lncRNA-mRNA co-expression network and the protein-protein interaction (PPI) network were constructed to identify hub regulatory lncRNAs and genes based on the microarray expression profiles. This study for the first time identifies an expression profile of differentially expressed lncRNAs in obese children and indicated hub lncRNA RP11-20G13.3 attenuated adipogenesis of preadipocytes, which is conducive to the search for new diagnostic and therapeutic strategies of childhood obesity.
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http://dx.doi.org/10.1038/s41598-018-27113-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5993825PMC
June 2018

miR-27a inhibits cervical adenocarcinoma progression by downregulating the TGF-βRI signaling pathway.

Cell Death Dis 2018 03 12;9(3):395. Epub 2018 Mar 12.

Department of Gynecology and Obstetrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.

High-risk human papillomavirus infection is essential for the malignant transformation of cervical cancer and can inhibit host miR-27a expression. We investigated the role and mechanism of miR-27a in cervical cancer progression. miR-27a is decreased in cervical cancer cell lines and miR-27a-agomir inhibited the cell proliferation, migration, and invasion properties of HeLa (adenocarcinoma) cells, but not in SiHa cells (squamous cell carcinoma). Luciferase assays revealed that miR-27a directly targets the 3'-UTR of transforming growth factor beta receptor I (TGF-βRI) and downregulates TGF-β signaling. The co-transfection of a TGF-βRI expression vector largely restored the inhibition of TGF-β signaling, cell proliferation, migration, and invasion mediated by miR-27a-agomir. Also, miR-27a-agomir slows down the growth of subcutaneous HeLa xenografts and downregulates the TGF-βRI expression and TGF-β signaling in tumor in vivo. Tissue microarray analysis revealed a low miR-27a level in adenocarcinoma cells, but not in squamous cell carcinoma cells, which was negatively associated with TGF-βRI expression. High TGF-βRI correlated with deep stromal invasion and lymph node metastasis. These results suggest that miR-27a acts as a tumor suppressor in cervical cancer, especially in adenocarcinoma, by inhibiting TGF-βRI signaling pathway. Thus, enhancing miR-27a expression and function may be a novel treatment strategy for cervical adenocarcinoma.
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http://dx.doi.org/10.1038/s41419-018-0431-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5847584PMC
March 2018

Wavelength selection for portable noninvasive blood component measurement system based on spectral difference coefficient and dynamic spectrum.

Spectrochim Acta A Mol Biomol Spectrosc 2018 Mar 26;193:40-46. Epub 2017 Nov 26.

State Key Laboratory of Precision Measurement Technology and Instruments, Tianjin University, Tianjin 300072, China; Tianjin Key Laboratory of Biomedical Detecting Techniques & Instruments, Tianjin University, Tianjin 300072, China. Electronic address:

Noninvasive blood component analysis by spectroscopy has been a hotspot in biomedical engineering in recent years. Dynamic spectrum provides an excellent idea for noninvasive blood component measurement, but studies have been limited to the application of broadband light sources and high-resolution spectroscopy instruments. In order to remove redundant information, a more effective wavelength selection method has been presented in this paper. In contrast to many common wavelength selection methods, this method is based on sensing mechanism which has a clear mechanism and can effectively avoid the noise from acquisition system. The spectral difference coefficient was theoretically proved to have a guiding significance for wavelength selection. After theoretical analysis, the multi-band spectral difference coefficient-wavelength selection method combining with the dynamic spectrum was proposed. An experimental analysis based on clinical trial data from 200 volunteers has been conducted to illustrate the effectiveness of this method. The extreme learning machine was used to develop the calibration models between the dynamic spectrum data and hemoglobin concentration. The experiment result shows that the prediction precision of hemoglobin concentration using multi-band spectral difference coefficient-wavelength selection method is higher compared with other methods.
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http://dx.doi.org/10.1016/j.saa.2017.10.063DOI Listing
March 2018

Reversible core-crosslinked nanocarriers with pH-modulated targeting and redox-controlled drug release for overcoming drug resistance.

J Mater Chem B 2017 Nov;5(42):8399-8407

Key Laboratory of Biomedical Polymers of Ministry of Education & College of Chemistry & Molecular Science, Wuhan University, Wuhan 430072, China.

Herein, a pH and redox dual-sensitive core-crosslinked targeting nanocarrier was prepared and used for co-delivery of doxorubicin (DOX) and tariquidar (TQR). The nanocarrier not only had excellent stability but also prevented the leakage of the drug in the normal physiological environment efficiently. Meanwhile, the targeting function of nanocarriers could also be suppressed in the normal physiological environment, protecting nanocarriers from being captured by RAW264.7 cells. Under mild acidic conditions, the targeting function was regained, leading to an effective tumor cell uptake of the nanocarrier. Furthermore, reduction-responsive drug release would occur in the cytoplasm due to the collapse of the reduction-sensitive crosslinked structure in the nanocarrier. By means of ligand-receptor mediated endocytosis and TQR-mediated glycoprotein (P-gp) inhibition, the IC50 value of DOX to MCF-7/ADR cells reduced from more than 100 μg mL-1 to 8.55 μg mL-1, exhibiting great potential in overcoming drug resistance.
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http://dx.doi.org/10.1039/c7tb01504fDOI Listing
November 2017

Noninvasive hemoglobin measurement using dynamic spectrum.

Rev Sci Instrum 2017 Aug;88(8):083109

School of Precision Instrument and Opto-Electronics Engineering, Tianjin University, Tianjin 300072, China.

Spectroscopy methods for noninvasive hemoglobin (Hgb) measurement are interfered by individual difference and particular weak signal. In order to address these problems, we have put forward a series of improvement methods based on dynamic spectrum (DS), including instrument design, spectrum extraction algorithm, and modeling approach. The instrument adopts light sources composed of eight laser diodes with the wavelength range from 600 nm to 1100 nm and records photoplethysmography signals at eight wavelengths synchronously. In order to simplify the optical design, we modulate the light sources with orthogonal square waves and design the corresponding demodulation algorithm, instead of adopting a beam-splitting system. A newly designed algorithm named difference accumulation has been proved to be effective in improving the accuracy of dynamic spectrum extraction. 220 subjects are involved in the clinical experiment. An extreme learning machine calibration model between the DS data and the Hgb levels is established. Correlation coefficient and root-mean-square error of prediction sets are 0.8645 and 8.48 g/l, respectively. The results indicate that the Hgb level can be derived by this approach noninvasively with acceptable precision and accuracy. It is expected to achieve a clinic application in the future.
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http://dx.doi.org/10.1063/1.4998978DOI Listing
August 2017

Synchronous acquisition of multi-channel signals by single-channel ADC based on square wave modulation.

Rev Sci Instrum 2017 Aug;88(8):085108

State Key Laboratory of Precision Measurement Technology and Instruments, Tianjin University, Tianjin 300072, China.

Synchronous acquisition of multi-channel biopotential signals, such as electrocardiograph (ECG) and electroencephalograph, has vital significance in health care and clinical diagnosis. In this paper, we proposed a new method which is using single channel ADC to acquire multi-channel biopotential signals modulated by square waves synchronously. In this method, a specific modulate and demodulate method has been investigated without complex signal processing schemes. For each channel, the sampling rate would not decline with the increase of the number of signal channels. More specifically, the signal-to-noise ratio of each channel is n times of the time-division method or an improvement of 3.01×logn dB, where n represents the number of the signal channels. A numerical simulation shows the feasibility and validity of this method. Besides, a newly developed 8-lead ECG based on the new method has been introduced. These experiments illustrate that the method is practicable and thus is potential for low-cost medical monitors.
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http://dx.doi.org/10.1063/1.4998990DOI Listing
August 2017

Cervical cancer cell-derived angiopoietins promote tumor progression.

Tumour Biol 2017 Jul;39(7):1010428317711658

1 Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China.

Metastatic or recurrent cervical cancer has limited treatment options and a high rate of mortality. Although anti-vascular endothelial growth factor drugs have shown great promise as a therapeutic target for treatment of advanced cervical cancer, drug resistance and class-specific side effects negate long-term benefits. The identification of alternative anti-angiogenic factors will be critical for future drug development for advanced or recurrent cervical cancer. In this study, we found that angiopoietins and Tie receptors were highly expressed in cervical cancer cells. Tie-2 expression in tumor cells predicted poorer prognosis. Wound closure assay and Transwell assay showed that upregulated or downregulated Ang-1 and Ang-2 expression promoted or reduced cervical cancer cell lines migration and invasion, respectively. In subcutaneous xenograft models of cervical cancer, downregulation of Ang-1 and Ang-2 attenuated tumor growth. The expression of vimentin and endomucin and microvessel density were all significantly decreased in the siAng-1 group and siAng-2 group relative to the infection control group. Our data support that dual inhibition of Ang-1 and Ang-2 may be an alternative target for anti-angiogenic adjuvant therapy in advanced or recurrent cervical squamous cell cancer.
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http://dx.doi.org/10.1177/1010428317711658DOI Listing
July 2017
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