Publications by authors named "Xueqin Zhu"

17 Publications

  • Page 1 of 1

VDAC1 as a target in cisplatin anti-tumor activity through promoting mitochondria fusion.

Biochem Biophys Res Commun 2021 May 7;560:52-58. Epub 2021 May 7.

Key Laboratory of Molecular Epidemiology of Hunan Province, School of Medicine, Hunan Normal University, Changsha, 410081, PR China. Electronic address:

Cisplatin is one of the most effective anti-cancer drugs, but its efficacy is limited by the development of resistance. Previous studies have shown that mitochondria play critical roles in cisplatin cytotoxicity, however, the exact mechanism of mitochondria involved in cisplatin sensitivity has not been clarified. In this study, cisplatin triggered mitochondrial oxidative stress and the decrease of mitochondria membrane potential in human cervical cancer cells. Then we screened a series of mitochondrial relevant inhibitors, including mitochondrial mPTP inhibitors DIDS and CsA, and mitochondrial respiratory complex inhibitors Rot and TTFA. Among these, only DIDS, as the inhibitor of mitochondrial outer membrane protein VDAC1, showed strong antagonism against cisplatin toxicity. DIDS mitigated cisplatin-induced MFN1-dependent mitochondrial fusion, mitochondrial dysfunction and oxidative damage. These findings demonstrated that VDAC1 may serve as a potential therapeutic target in the increase sensitivity of cisplatin, which provides an attractive pharmacological therapy to improve the effectiveness of chemotherapy.
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http://dx.doi.org/10.1016/j.bbrc.2021.04.104DOI Listing
May 2021

An orally available PD-1/PD-L1 blocking peptide OPBP-1-loaded trimethyl chitosan hydrogel for cancer immunotherapy.

J Control Release 2021 May 1;334:376-388. Epub 2021 May 1.

School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Shenzhen 518107, China; School of Life Sciences, Zhengzhou University, Zhengzhou 450001, China. Electronic address:

Blockade of the immune checkpoint PD-1/PD-L1 with monoclonal antibodies demonstrated unprecedented clinical efficacies in many cancers. But the orally available low molecular weight inhibitors remain infancy. Compared to small molecules, peptide exhibits better selectivity and fewer side effects, but poor half-life and a big challenge to be orally administrated. Here, we developed a proteolysis-resistant D peptide OPBP-1 (Oral PD-L1 Binding Peptide 1) which could selectively bind PD-L1, significantly block PD-1/PD-L1 interaction and enhance IFN-γ (interferon γ) secretion from CD8 T cells in human PBMCs (Peripheral blood mononuclear cells). OPBP-1 could significantly inhibit tumor growth in murine colorectal CT26 and melanoma B16-OVA models at a relatively low dose of 0.5 mg/kg, with enhancing the infiltration and function of CD8 T cells. More interestingly, oral delivery of OPBP-1 loaded TMC (N, N, N-trimethyl chitosan) hydrogel (OPBP-1@TMC) showed promising OPBP-1 oral bioavailability (52.8%) and prolonged half-life (14.55 h) in rats, and also significantly inhibited tumor growth in CT26 model. In conclusion, we discovered and optimized a PD-1/PD-L1 blocking peptide OPBP-1, and subsequently loaded into a TMC based hydrogel oral delivery system, in order to maximally elevate the oral bioavailability of the peptide drug and effectively inhibit tumor growth. These results opened up a new prospect for oral drug development in cancer immunotherapy.
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http://dx.doi.org/10.1016/j.jconrel.2021.04.036DOI Listing
May 2021

Hydrochemical characterization and quality assessment of groundwater in the hilly area of the Taihang Mountains in Henan Province, China.

Environ Sci Pollut Res Int 2021 Apr 10. Epub 2021 Apr 10.

Henan Institute of Geological Environment Monitoring, Zhengzhou, 450016, China.

This study evaluated the quality of groundwater and its suitability for drinking and irrigation in the hilly area of the Taihang Mountains in Henan Province, China. Groundwater samples were collected from 43 unconfined and 20 confined wells and analyzed. The pollution index of groundwater (PIG) was estimated based on the physicochemical parameters, and seven indices, including the sodium adsorption ratio (SAR), sodium percentage (%Na), residual sodium carbonate (RSC), permeability index (PI), magnesium ratio (MR), Kelley's ratio (KR), and corrosivity ratio (CR), were calculated to qualify the groundwater within the research area for irrigation activities. Multivariate statistical techniques were performed to better understand the hydrochemical processes. Chemical analysis showed that the dominant cation and anion were Ca and HCO, respectively, and the principal hydrochemical facies was Ca-Mg-HCO. In terms of pH, total dissolved solids, Na, Cl, F, and SO, most samples were well within the limits prescribed by Chinese standards for drinking water quality, but more than half of the unconfined samples exceeded the specified limits for total hardness and nitrate. The PIG values suggested the pollution level was insignificant for all confined water samples and 72.09% of unconfined water samples, but the PIG distribution map showed that the water in the south central part of the study area had low to moderate pollution. According to the computed values of SAR, %Na, RSC, PI, KR, and MR and the results of a salinity diagram, the results further indicated that most of the studied samples were appropriate for irrigation usage. Only the CR values rendered 41.86% of the unconfined samples and 20% of the confined samples unfit for irrigation. Hence, proper measures are needed to resolve the corrosivity problem. Factor analysis resulted in the extraction of 3 factors that explained 81% of the data variability, and the extracted factors pointed towards geogenic factors governing the groundwater quality.
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http://dx.doi.org/10.1007/s11356-021-13579-1DOI Listing
April 2021

Berberine ameliorates the LPS-induced imbalance of osteogenic and adipogenic differentiation in rat bone marrow-derived mesenchymal stem cells.

Mol Med Rep 2021 May 24;23(5). Epub 2021 Mar 24.

Department of Stomatology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, P.R. China.

Lipopolysaccharide (LPS) from oral pathogenic bacteria is an important factor leading to alveolar bone absorption and the implant failure. The present study aimed to evaluate the modulation of berberine hydrochloride (BBR) on the LPS-mediated osteogenesis and adipogenesis imbalance in rat bone marrow-derived mesenchymal stem cells (BMSCs). Cell viability, osteoblastic and adipogenic differentiation levels were measured using the Cell Counting Kit-8 assay, alkaline phosphatase (ALP) staining and content assay, and oil red O staining, respectively. Reverse transcription-quantitative PCR and immunoblotting were used to detect the related gene and protein expression levels. In undifferentiated cells, BBR increased the mRNA expression levels of the osteoblastic genes (Alp, RUNX family transcription factor 2, osteocalcin and secreted phosphoprotein 1) but not the adipogenic genes (fatty acid binding protein 4, Adipsin and peroxisome proliferator-activated receptorγ). LPS-induced osteoblastic gene downregulation, adipogenic gene enhancement and NF-κB activation were reversed by BBR treatment. In osteoblastic differentiated cells, decreased ALP production by LPS treatment was recovered with BBR co-incubation. In adipogenic differentiated cells, LPS-mediated lipid accumulation was decreased by BBR administration. The mRNA expression levels of the pro-inflammatory factors (MCP-1, TNF-α, IL-6 and IL-1β) were increased by LPS under both adipogenic and osteoblastic conditions, which were effectively ameliorated by BBR. The actions of BBR were attenuated by compound C, suggesting that the role of BBR may be partly due to AMP-activated protein kinase activation. The results demonstrated notable pro-osteogenic and anti-adipogenic actions of BBR in a LPS-stimulated inflammatory environment. This indicated a potential role of BBR for bacterial infected-related peri-implantitis medication.
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http://dx.doi.org/10.3892/mmr.2021.11989DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7974461PMC
May 2021

Effects of N-Linked Glycan on Lassa Virus Envelope Glycoprotein Cleavage, Infectivity, and Immune Response.

Virol Sin 2021 Mar 10. Epub 2021 Mar 10.

State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, 430071, China.

Lassa virus (LASV) belongs to the Mammarenavirus genus (family Arenaviridae) and causes severe hemorrhagic fever in humans. The glycoprotein complex (GPC) contains eleven N-linked glycans that play essential roles in GPC functionalities such as cleavage, transport, receptor recognition, epitope shielding, and immune response. We used three mutagenesis strategies (asparagine to glutamine, asparagine to alanine, and serine/tyrosine to alanine mutants) to abolish individual glycan chain on GPC and found that all the three strategies led to cleavage inefficiency on the 2nd (N89), 5th (N119), or 8th (N365) glycosylation motif. To evaluate N to Q mutagenesis for further research, it was found that deletion of the 2nd (N89Q) or 8th (N365Q) glycan completely inhibited the transduction efficiency of pseudotyped particles. We further investigated the role of individual glycan on GPC-mediated immune response by DNA immunization of mice. Deletion of the individual 1st (N79Q), 3rd (N99Q), 5th (N119Q), or 6th (N167Q) glycan significantly enhanced the proportion of effector CD4 cells, whereas deletion of the 1st (N79Q), 2nd (N89Q), 3rd (N99Q), 4th (N109Q), 5th (N119Q), 6th (N167Q), or 9th (N373Q) glycan enhanced the proportion of CD8 effector T cells. Deletion of specific glycan improves the Th1-type immune response, and abolishment of glycan on GPC generally increases the antibody titer to the glycan-deficient GPC. However, the antibodies from either the mutant or WT GPC-immunized mice show little neutralization effect on wild-type LASV. The glycan residues on GPC provide an immune shield for the virus, and thus represent a target for the design and development of a vaccine.
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http://dx.doi.org/10.1007/s12250-021-00358-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7945000PMC
March 2021

In vitro anti‑bacterial activity of diosgenin on Porphyromonas gingivalis and Prevotella intermedia.

Mol Med Rep 2020 Dec 21;22(6):5392-5398. Epub 2020 Oct 21.

Department of Stomatology, Shanghai 10th People's Hospital of Tongji University, Shanghai 200072, P.R. China.

Diosgenin (Dios), a natural steroidal sapogenin, is a bioactive compound extracted from dietary fenugreek seeds. It has a wide range of applications, exhibiting anti‑oxidant, anti‑inflammatory and anti‑cancer activities. However, whether the extracts have beneficial effects on periodontal pathogens has so far remained elusive. The aim of the present study was to investigate the anti‑bacterial effects of Dios on Porphyromonas gingivalis (P. gingivalis) and Prevotella intermedia (P. intermedia) in vitro. The anti‑microbial effect of Dios on P. gingivalis and P. intermedia was assessed by a direct contact test (DCT) and the Cell Counting Kit (CCK)‑8 assay at 60, 90 and 120 min. In addition, counting of colony‑forming units (CFU) and live/dead cell staining were used to evaluate the anti‑bacterial effects. The results of the DCT and CCK‑8 assays indicated that Dios had beneficial dose‑dependent inhibitory effects on P. gingivalis and P. intermedia. The CFU counting results also indicated that Dios had dose‑dependent anti‑bacterial effects on P. gingivalis and P. intermedia. Of note, Dios had significant anti‑bacterial effects on the biofilms of P. gingivalis and P. intermedia in vitro as visualized by the live/dead cell staining method. In conclusion, the present results demonstrated that Dios had a marked anti‑bacterial activity against P. gingivalis and P. intermedia in vitro, both in suspension and on biofilms. The present study highlighted the potential applications of Dios as a novel natural agent to prevent and treat periodontitis through its anti‑bacterial effects.
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http://dx.doi.org/10.3892/mmr.2020.11620DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7647021PMC
December 2020

Oral cancer cell‑derived exosomes modulate natural killer cell activity by regulating the receptors on these cells.

Int J Mol Med 2020 Dec 24;46(6):2115-2125. Epub 2020 Sep 24.

Department of Oral and Maxillofacial‑Head and Neck Oncology and Faculty of Oral and Maxillofacial Surgery, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, P.R. China.

Oral cancer (OC) is the most common type of head and neck malignant tumor. Tumor‑derived exosomes induce a complex extracellular environment that affects tumor immunity. In the present study, exosomes were isolated from OC cell lines (WSU‑HN4 and SCC‑9) by ultrafiltration and the protein content of these oral cancer‑derived exosomes (OCEXs) was analyzed by mass spectrometry, which revealed the enrichment of transforming growth factor (TGF)‑β1. Natural killer (NK) cells were examined by flow cytometry following co‑culture with OCEXs. The expression of killer cell lectin like receptor K1 (KLRK1; also known as NKG2D, as used herein) and natural cytotoxicity triggering receptor 3 (NCR3; also known as NKp30, as used herein) in NK cells was found to be significantly upregulated following co‑culture with the OCEXs for 1 day, whereas this expression decreased at 7 days. Killer cell lectin like receptor C1 (KLRC1; also known as NKG2A; as used herein) expression exhibited an opposite trend at 1 day. In addition, NK cell cytotoxicity against the OC cells was enhanced at 1 day, but was attenuated at 7 days. TGF‑β1 inhibited the function of NK cells at 7 days, whereas it had no obvious effects at 1 and 3 days. On the whole, the findings of the present study reveal changes in NK cell function and provide new insight into NK cell dysfunction.
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http://dx.doi.org/10.3892/ijmm.2020.4736DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7595664PMC
December 2020

Knockout of NRAGE promotes autophagy-related gene expression and the periodontitis process in mice.

Oral Dis 2021 Apr 20;27(3):589-599. Epub 2020 Aug 20.

Department of Stomatology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.

Background And Objective: Neurotrophin receptor-interacting MAGE homologue (NRAGE) plays a crucial role in the regulation of bone metabolism. The present study investigated the regulation role of NRAGE on autophagy activation and periodontitis process during experimental periodontitis.

Materials And Methods: Six-week-old wild-type (WT) and NRAGE-/- mice were randomly divided into three time points in the periodontitis groups (0, 2, and 4 weeks). Histopathological changes were determined using the tooth mobility, hematoxylin and eosin (H&E) staining, and micro-computed tomography (micro-CT). Osteoclasts activation and number were investigated using tartrate-resistant acid phosphatase (TRAP) staining, immunohistochemistry, and real-time quantitative PCR (RT-PCR). The level of autophagy-related gene expression was measured using immunohistochemistry, immunofluorescence, and RT-PCR.

Results: H&E staining and Micro-CT showed that the destruction of the alveolar bone was considerably more severe in the NRAGE-/- group than the WT group after ligation. Tooth mobility in the NRAGE-/- group was obviously higher than that in the WT group. The activation and number of osteoclasts and the level of autophagy-related gene expression in NRAGE-/- group were significantly higher than that in WT group.

Conclusions: The present study showed that knockout of NRAGE induced autophagy-related gene expression and accelerated the process of periodontitis disease via increasing the activity and differentiation of osteoclast.
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http://dx.doi.org/10.1111/odi.13575DOI Listing
April 2021

Exosomal miR-196a derived from cancer-associated fibroblasts confers cisplatin resistance in head and neck cancer through targeting CDKN1B and ING5.

Genome Biol 2019 01 14;20(1):12. Epub 2019 Jan 14.

Department of Oral and Maxillofacial-Head & Neck Oncology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Road, Shanghai, 200011, People's Republic of China.

Background: Cisplatin resistance is a major challenge for advanced head and neck cancer (HNC). Understanding the underlying mechanisms and developing effective strategies against cisplatin resistance are highly desired in the clinic. However, how tumor stroma modulates HNC growth and chemoresistance is unclear.

Results: We show that cancer-associated fibroblasts (CAFs) are intrinsically resistant to cisplatin and have an active role in regulating HNC cell survival and proliferation by delivering functional miR-196a from CAFs to tumor cells via exosomes. Exosomal miR-196a then binds novel targets, CDKN1B and ING5, to endow HNC cells with cisplatin resistance. Exosome or exosomal miR-196a depletion from CAFs functionally restored HNC cisplatin sensitivity. Importantly, we found that miR-196a packaging into CAF-derived exosomes might be mediated by heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1). Moreover, we also found that high levels of plasma exosomal miR-196a are clinically correlated with poor overall survival and chemoresistance.

Conclusions: The present study finds that CAF-derived exosomal miR-196a confers cisplatin resistance in HNC by targeting CDKN1B and ING5, indicating miR-196a may serve as a promising predictor of and potential therapeutic target for cisplatin resistance in HNC.
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http://dx.doi.org/10.1186/s13059-018-1604-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6332863PMC
January 2019

Periostin secreted by cancer-associated fibroblasts promotes cancer stemness in head and neck cancer by activating protein tyrosine kinase 7.

Cell Death Dis 2018 10 22;9(11):1082. Epub 2018 Oct 22.

Department of Oral and Maxillofacial-Head & Neck Oncology, Shanghai Ninth People's Hospital & College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China.

Protein tyrosine kinase 7 (PTK7) and cancer-associated fibroblasts (CAFs) play important roles in cancer stemness, respectively. However, little is known about interaction between CAFs and PTK7 in cancers. In this study, we showed that PTK7 was significantly correlated with the Wnt/β-Catenin pathway and aggressive clinicopathologic features in human head and neck squamous cell carcinoma (HNSCC). Meanwhile, animal experiments showed that PTK7 enhanced chemoresistance and lung metastasis of HNSCC in vivo. In addition, co-immunoprecipitation (co-IP) assay demonstrated that POSTN secreted by CAFs was a potential upstream ligand of PTK7 which might act as a receptor. Further analysis revealed that POSTN promoted the cancer stem cell (CSC)-like phenotype via PTK7-Wnt/β-Catenin signaling, including the proliferation and invasion of HNSCC cells in vitro, as well as tumor initiation and progression in vivo. Collectively, our study proved that CAF-derived POSTN might promote cancer stemness via interacting with PTK7 in HNSCC, suggesting that the combination of POSTN and PTK7 might be a potential prognostic and diagnostic indicator and a  promising therapeutic target.
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http://dx.doi.org/10.1038/s41419-018-1116-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6197282PMC
October 2018

Association of expression of rs1800497 polymorphism with migraine risk in Han Chinese individuals.

J Pain Res 2018 12;11:763-769. Epub 2018 Apr 12.

Department of Anesthesiology, The Affiliated Hospital of Medical School, Ningbo University, Ningbo, China.

Background: Previous studies suggested that single-nucleotide polymorphisms in dopamine receptor D2 () are the susceptibility loci for migraine. This study was aimed at evaluating the contribution of rs1800497 and its expression to migraine risk in Han Chinese subjects.

Methods: In total, 250 patients with migraine and 250 age- and sex-matched control subjects were included in this study. TaqMan allelic discrimination assay was used for rs1800497 genotyping. Plasma DRD2 concentration was determined using enzyme-linked immunosorbent assay.

Results: Significant associations were observed for the rs1800497 genotype (=6.37, =0.041) and allele (=4.69, =0.03; odds ratio [OR]=1.33, 95% CI=1.03-1.72, power=58%) frequencies between the migraine and control groups. Sex analysis indicated a positive association for rs1800497 between female patients with migraine and control individuals (genotype: =7.84, =0.019; allele: =6.60, =0.010; OR=1.61, 95% CI=1.12-2.30, power=73.4%). Furthermore, a significant association was observed only in female patients with migraine without aura (MO) (genotype: =6.88, =0.032; allele: =5.65, =0.017; OR=1.59, 95% CI=1.08-2.36, power=65.1%). The mean plasma DRD2 levels in the control group (mean±SD: 24.20±2.78) were significantly lower than those in the migraine with aura (MA) (30.86±3.69, <0.0001) and MO groups (31.88±4.99, <0.0001). Additionally, there was a sex-based difference in DRD2 expression in the MA (male vs female: 29.46±3.59 vs 32.27±3.27, <0.01) and MO groups (male vs female: 29.18±3.50 vs 34.58±4.84, <0.0001). Moreover, plasma DRD2 levels in patients were significantly different among the three genotypes (CC vs CT vs TT: 24.76±3.76 vs 30.93±3.85 vs 37.06±3.95, <0.0001). Similar results were observed both in the MA (CC vs CT vs TT: 25.09±3.84 vs 28.57±2.84 vs 33.37±1.58, <0.0001) and MO groups (CC vs CT vs TT: 24.65±3.79 vs 31.65±3.86 vs 38.29±3.74, <0.0001).

Conclusion: Our case-control study suggested that the polymorphism rs1800497 was significantly associated with the risk of migraine in Han Chinese females. Additionally, the plasma DRD2 level was high in patients with migraine. Females with migraine had considerably higher DRD2 levels than males with migraine. DRD2 expression may be regulated by rs1800497 genotype in patients with migraine.
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http://dx.doi.org/10.2147/JPR.S151350DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5905461PMC
April 2018

Cancer-associated Fibroblast-derived IL-6 Promotes Head and Neck Cancer Progression via the Osteopontin-NF-kappa B Signaling Pathway.

Theranostics 2018 1;8(4):921-940. Epub 2018 Jan 1.

Department of Oral and Maxillofacial-Head & Neck Oncology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, PR China.

Osteopontin (OPN), a chemokine-like protein, plays a crucial role in the proliferation and metastasis of various cancers. However, how tumor stroma modulates the expression of neoplastic OPN and the multifaceted roles of OPN in head and neck cancer (HNC) are unclear. In this study, we tried to investigate the bridging role of OPN between tumor stroma and cancer cells. Immunohistochemical staining and quantitative real-time PCR were used to detect OPN expression in HNC tissues, and the correlations between OPN expression and clinicopathologic features were then analyzed. We used a co-culture assay to study the modulatory role of IL-6 on OPN expression and immunoprecipitation analysis was used to determine the endogenous interaction between OPN and integrin αvβ3. Furthermore, a xenograft assay was carried out to confirm the tumor-promoting role and the potential therapeutic value of OPN in HNC. We found that OPN was significantly up-regulated in HNCs, and the elevated OPN was correlated with poor prognosis. Moreover, we identified IL-6 secreted by cancer-associated fibroblasts (CAFs) as the major upstream molecule that triggers the induction of neoplastic OPN. As such, during the interaction of fibroblasts and cancer cells, the increased neoplastic OPN induced by stromal IL-6 accelerated the growth, migration and invasion of cancer cells. More importantly, we also showed that soluble OPN could promote HNC progression via the integrin αvβ3-NF-kappa B pathway, and the combination of OPN and IL-6 had a better prognostic and diagnostic performance in HNC than either molecule alone. Our study identified a novel modulatory role for OPN in HNC progression and further demonstrated that the combination of OPN and IL-6 might be a promising prognostic and diagnostic indicator as well as a potential cancer therapeutic target.
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http://dx.doi.org/10.7150/thno.22182DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5817102PMC
January 2019

Corrigendum to "Oral cancer-derived exosomal NAP1 enhances cytotoxicity of natural killer cells via the IRF-3 pathway" [Oral Oncol. 76 (2018) 34-41].

Oral Oncol 2018 03 1;78:228. Epub 2018 Feb 1.

Department of Oral and Maxillofacial-Head and Neck Oncology and Faculty of Oral and Maxillofacial Surgery, Ninth People's Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai 200011, PR China; Shanghai Key Laboratory of Stomatology and Shanghai Research Institute of Stomatology, Shanghai 200011, PR China. Electronic address:

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http://dx.doi.org/10.1016/j.oraloncology.2018.01.007DOI Listing
March 2018

Oral cancer-derived exosomal NAP1 enhances cytotoxicity of natural killer cells via the IRF-3 pathway.

Oral Oncol 2018 01;76:34-41

Department of Oral and Maxillofacial-Head and Neck Oncology and Faculty of Oral and Maxillofacial Surgery, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, PR China; Shanghai Key Laboratory of Stomatology and Shanghai Research Institute of Stomatology, Shanghai 200011, PR China. Electronic address:

Objective: To examine the effects of oral cancer-derived exosomes (OCEXs) on natural killer (NK) cells and to explore the underlying mechanism.

Materials And Methods: OCEXs were isolated from the cell culture supernatant of oral cancer (OC) cells using ultrafiltration and affinity chromatography and were identified using electron microscopy, nanoparticle tracking analysis (NTA) and immunoblotting. The effects of OCEXs on NK cells were analyzed using laser scanning confocal microscopy and several functional assays of NK cells. To explore the mechanism of their effects, antibody array, protein mass spectrometry and RNA interference were adopted.

Results: The particles isolated from the OC cells were identified as exosomes with satisfactory morphology, concentration and purity. The OCEXs were internalized by NK cells and then promoted the biological functions of NK cells, including proliferation, release of perforin and granzyme M and cytotoxicity. Furthermore, OCEXs increased the expression of interferon regulatory factor 3 (IRF-3) and its phosphorylation, which drove the expression of the type I interferon (IFN) gene and the chemokine (C-X-C motif) ligand (CXCL) genes, thereby promoting the functions of NK cells. In addition, NF-κB-activating kinase-associated protein 1 (NAP1), an upstream activator of IRF-3, was enriched in OCEXs, and treatment with OCEXs increased the expression of NAP1 in NK cells. Importantly, NAP1-depleted OCEXs obtained from OC cells had a dramatically weakened influence on NK cells.

Conclusion: Our findings reveal a previously unrecognized function of exosomal NAP1 derived from OC cells in enhancing the cytotoxicity of NK cells via the IRF-3 pathway.
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http://dx.doi.org/10.1016/j.oraloncology.2017.11.024DOI Listing
January 2018

Role of protein delta homolog 1 in the proliferation and differentiation of ameloblasts.

Mol Med Rep 2018 Mar 18;17(3):3537-3544. Epub 2017 Dec 18.

Department of Oral and Maxillofacial‑Head and Neck Oncology, and Faculty of Oral and Maxillofacial Surgery, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, P.R. China.

Protein delta homolog 1 (DLK1) regulates the odontoblastic differentiation of human dental pulp stem cells. It was hypothesized that DLK1 may exert regulatory effects on epithelial‑mesenchymal interactions in tooth development. The present study investigated the expression of DLK1 during the development of mouse enamel and its role in the proliferation and differentiation of ameloblast‑lineage cells (ALCs). DLK1 expression was upregulated in ameloblasts in the first mandibular molar during the entire process of enamel development. The mRNA and protein levels of DLK1 were significantly upregulated following ameloblastic induction in ALCs. In addition, overexpression of DLK1 promoted the proliferation of ALCs, inhibited ameloblastic differentiation, upregulated the expression of amelogenin and enamelin, and downregulated the expression of odontogenic ameloblast‑associated protein and kallikrein 4. The results of the present study suggested that DLK1 may be a potent regulator of ameloblast proliferation and differentiation, and may regulate enamel formation during tooth development.
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http://dx.doi.org/10.3892/mmr.2017.8290DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5802151PMC
March 2018

Identify stakeholders' understandings of life cycle assessment results on wastewater related issues.

Sci Total Environ 2018 May 13;622-623:869-874. Epub 2017 Dec 13.

State Key Laboratory of Urban Water Resource and Environment, School of Environment, Harbin Institute of Technology, Harbin 150090, China. Electronic address:

To facilitate decision-making processes in waste management, it is important to not only evaluate environmental impacts, but also to measure how stakeholders form opinions and make choices based one valuation results. Life cycle assessments (LCAs) have been widely used to evaluate environmental impacts; however, LCAs cannot be used to measure how people make judgments based on evaluation results. As such, in this study, we combined LCA with conjoint analysis, an economic method that allows individuals to consider all factors and demonstrate their preferences simultaneously. We used this combined method in a case study on wastewater treatment, and obtained two major types of estimation results: (1) the relative importance of each impact category of LCA, and (2) the overall preferences of respondents for each alternative. This study also highlighted some issues regarding the combination of methodologies, such as the selection of impact categories in LCA, the conversion of impact categories into understandable attributes for conjoint analysis, and weaknesses in conjoint analysis that need to be addressed and corrected in future studies.
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http://dx.doi.org/10.1016/j.scitotenv.2017.12.034DOI Listing
May 2018

The ubiquitin-proteasome system is essential for the productive entry of Japanese encephalitis virus.

Virology 2016 11 25;498:116-127. Epub 2016 Aug 25.

State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China; University of the Chinese Academy of Sciences, Beijing, China. Electronic address:

The host-virus interaction during the cellular entry of Japanese encephalitis virus (JEV) is poorly characterized. The ubiquitin-proteasome system (UPS), the major intracellular proteolytic pathway, mediates diverse cellular processes, including endocytosis and signal transduction, which may be involved in the entry of virus. Here, we showed that the proteasome inhibitors, MG132 and lactacystin, impaired the productive entry of JEV by effectively interfering with viral intracellular trafficking at the stage between crossing cell membrane and the initial translation of the viral genome after uncoating. Using confocal microscopy, it was demonstrated that a proportion of the internalized virions were misdirected to lysosomes following treatment with MG132, resulting in non-productive entry. In addition, using specific siRNAs targeting ubiquitin, we verified that protein ubiquitination was involved in the entry of JEV. Overall, our study demonstrated the UPS is essential for the productive entry of JEV and might represent a potential antiviral target for JEV infection.
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http://dx.doi.org/10.1016/j.virol.2016.08.013DOI Listing
November 2016