Publications by authors named "Lin Que"

19 Publications

  • Page 1 of 1

Upper-Critical-Solution-Temperature Polymer Modified Gold Nanorods for Laser Controlled Drug Release and Enhanced Anti-Tumour Therapy.

Front Pharmacol 2021 23;12:738630. Epub 2021 Sep 23.

Department of Biliary Surgery, West China Hospital of Sichuan University, Chengdu, China.

Photothermal therapy (PTT) has become effective method for the treatment of malignant cancer. The development of PTT system with high anti-tumour effect is still the feasible research direction. Here, a new type of gold nanorods (AuNRs)-doxorubicin (DOX)/mPEG-peptide/P(AAm-co-AN) (APP-DOX) nano drug delivery system was proposed. Among them, AuNRs was used as high-efficiency photothermal agent. APP-DOX had a suitable size and can be targeted to accumulate in tumour tissues through circulation in the body. The abundant matrix metalloproteinase 2 (MMP-2) in the tumour environment intercepted and cut off the short peptide chain structure grafted on APP-DOX. At the same time, the removal of the PEG segment leaded to an increase in the hydrophobic properties of the system. Nanoparticles aggregated into large particles, causing them to stay and aggregate further at the tumour site. When irradiated by 808 nm near-infrared laser, APP-DOX achieved a gradual heating process. High temperature can effectively ablate tumours and enable UCST polymer to achieve phase transition, resulting in more anti-cancer drugs loaded in the polymer layer DOX was released, effectively killing cancer cells. Animal experiments had verified the possibility of the nano drug-carrying system and good tumour treatment effect. What's more worth mentioning is that compared with free DOX, the nano drug delivery system had lower biological toxicity and not cause obvious harmful effects on normal organs and tissues.
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http://dx.doi.org/10.3389/fphar.2021.738630DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8495017PMC
September 2021

Recurrent rewiring of the adult hippocampal mossy fiber system by a single transcriptional regulator, Id2.

Proc Natl Acad Sci U S A 2021 10;118(40)

Laboratory of Neural Connectivity, Brain Research Institute, Faculties of Medicine and Science, University of Zürich, Zürich, 8057, Switzerland;

Circuit formation in the central nervous system has been historically studied during development, after which cell-autonomous and nonautonomous wiring factors inactivate. In principle, balanced reactivation of such factors could enable further wiring in adults, but their relative contributions may be circuit dependent and are largely unknown. Here, we investigated hippocampal mossy fiber sprouting to gain insight into wiring mechanisms in mature circuits. We found that sole ectopic expression of Id2 in granule cells is capable of driving mossy fiber sprouting in healthy adult mouse and rat. Mice with the new mossy fiber circuit solved spatial problems equally well as controls but appeared to rely on local rather than global spatial cues. Our results demonstrate reprogrammed connectivity in mature neurons by one defined factor and an assembly of a new synaptic circuit in adult brain.
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http://dx.doi.org/10.1073/pnas.2108239118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8501755PMC
October 2021

Prevalence of dental caries in the first permanent molar and associated risk factors among sixth-grade students in São Tomé Island.

BMC Oral Health 2021 09 28;21(1):483. Epub 2021 Sep 28.

Ministry of Health, Água Grand, São Tomé and Príncipe.

Background: Dental caries is one of the most preventable oral diseases among children in developing countries. This study aims to estimate the prevalence and severity of dental caries in the first permanent molar and analyze the related risk factors among sixth-grade students in São Tomé Island.

Methods: A cross-sectional study with a stratified cluster sampling method was conducted on 1855 sixth-grade school children, mainly aged 11 to 14 years old, from 10 schools in 6 regions of São Tomé Island, from April 17 to June 27, 2021. Dental caries examination was performed by using the CAST criteria (DMFT) index, and the self-administered questionnaires about family background, oral hygiene, and relevant behaviors were collected. Multivariable logistic regression was used to study risk factors related to dental caries of the first permanent molar, and all data analyses were done using SPSS version 25.

Results: The prevalence of dental caries in the first permanent molar was 68.79%, without significant difference between gender, age, residence, and whether only child or not. The mean Decayed, Missing, and Filled Teeth (DMFT) index and mean Decayed, Missing, and Filled Surface (DMFS) index were 1.751 ± 1.514 and 3.542 ± 3.941, respectively. The rate of filling teeth was 5.50%, and Pit and Fissure Sealant (PFS) rate was 2.21%. The overall prevalence and DMFT index of dental caries of permanent teeth was 76.01% and 2.753 ± 4.569, respectively. The results of logistic regression analysis indicated that the frequency of candy/chocolate consumption (OR = 1.095) and fair self-assessment of dental health (OR = 1.354) were significantly associated with dental caries (P < 0.05).

Conclusions: The high prevalence of dental caries in the first permanent molar was a public health issue among sixth-grade school children in São Tomé Island. The prevalence of dental caries, mean DMFT and DMFS scores were higher, while the rate of filling and PFS teeth were lower than the average score of other African countries. Thus, oral health education, implement oral health preaching to school children and their parents is crucial to prevent dental caries.
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http://dx.doi.org/10.1186/s12903-021-01846-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8479893PMC
September 2021

Effect of piceatannol against malignant melanoma and .

Hua Xi Kou Qiang Yi Xue Za Zhi 2021 Aug;39(4):413-418

State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Dept. of Head and Neck Oncology, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China.

Objectives: To study the antitumor effect of piceatannol (PIC) on malignant melanoma and .

Methods: B16F10 cells were cultured and treated with gradient concentrations of PIC. Cell viability was detected with methyl thiazolyl tetrazolium (MTT) assay; matrix metalloproteinase (MMP)-2, MMP-9, vascular endothelial growth factor (VEGF), spleen tyrosine kinase (Syk), and p-Syk were detected with Western blot; migration ability was detected with wound healing assay; invasion ability was detected with Transwell assay. Syk expression was suppressed through RNA interference for the detection of the possible mechanism of PIC in melanoma. An study was established by creating B16F10-bearing mice with intraperitoneal injection of PIC.

Results: The cell viability of B16F10 decreased with increasing PIC concentration. The results of the Transwell assay showed that invasion ability decreased with increasing PIC concentration, and healing time was prolonged at increased PIC concentration in the wound healing assay. Western blot results showed that PIC mainly inhibited the phosphorylation of Syk and inhibited the expression of MMP-2, MMP-9, and VEGF. RNA interference pointed out that blocking the expression of Syk can reveal the same inhibition effect on B16F10 cells as PIC. study revealed that different concentrations of PIC cangreatly inhibit melanoma progression.

Conclusions: PIC might block the progression of malignant melanoma by inhibiting spleen tyrosine kinase.
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http://dx.doi.org/10.7518/hxkq.2021.04.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8381120PMC
August 2021

Prognostic Value of Perineural Invasion in Oral Tongue Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis.

Front Oncol 2021 12;11:683825. Epub 2021 Jul 12.

State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.

Objectives: A significant number of recently published research has outlined the contribution of perineural invasion (PNI) to clinical outcomes in oral tongue squamous cell carcinoma (OTSCC), but some results remain conflicting. This study aimed to determine whether patients with OTSCC with PNI have a worse prognosis than those without PNI.

Materials And Methods: PubMed, Embase, and the Cochrane Library were queried for potentially eligible articles published up to December 2020. The primary outcomes were the hazard ratio (HR) for locoregional recurrence, overall survival (OS), disease-free survival (DFS), and cancer-specific survival (CSS). The random-effect model was used in all analyses.

Results: Seventeen studies (4445 patients) were included. Using adjusted HRs, the presence of PNI was associated with a higher risk of locoregional recurrence (HR=1.73, 95%CI: 1.07-2.79, P=0.025, I = 33.1%, P=0.224), worse OS (HR=1.94, 95%CI: 1.39-2.72, P<0.001, I = 0.0%, P=0.838), worse DFS (HR=2.13, 95%CI: 1.53-2.96, P<0.001, I = 48.4%, P=0.071), and worse CSS (HR=1.93, 95%CI: 1.40-2.65, P<0.001, I = 25.5%, P=0.251). PNI had an impact on locoregional recurrence in early-stage OTSCC but not in all stages, and on OS, DFS, and CSS in all-stage and early-stage OTSCC. The sensitivity analyses showed that the results were robust.

Conclusion: The presence of PNI significantly affects the locoregional recurrence and survival outcomes among patients with OTSCC.
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http://dx.doi.org/10.3389/fonc.2021.683825DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8311439PMC
July 2021

Smad7 attenuates TGF-β-mediated aging-related hypofunction of submandibular glands.

Exp Biol Med (Maywood) 2021 06 27;246(11):1269-1273. Epub 2021 Feb 27.

Department of Head and Neck Oncology, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China.

Submandibular glands have essential functions in taste, mastication, swallowing, and digestion. Submandibular gland hypofunction is prevalent in the elderly, impairing the patients' quality of life. Current clinical treatment strategies have not decelerated or reversed the pathological process of submandibular gland hypofunction. Therefore, novel restoration strategies should be explored. However, studies on the mechanism of aging-related submandibular gland hypofunction remain very limited. The role of the TGF-β/Smad pathway in fibrosis has been studied in other organs. Therefore, this study aimed to elucidate the role of TGF-β/Smad signaling in the aging-related submandibular gland hypofunction. The results showed that Smad7 knockout in mice decreased the salivary flow rate. H&E, Masson trichrome, and immunohistochemistry staining of MCP-1 and α-SMA showed that Smad7 knockout in mice resulted in lymphocytic infiltration, acinar cell atrophy, and interstitial fibrosis. The Western blotting of collagen I and III also confirmed extensive fibrosis. We then found that Smad7 depletion resulted in the TGF-β-mediated fibrosis via mir-21, mir-29, and np_5318, and NFκB-driven inflammation activation. This study confirmed the inhibitory role of Smad7 in the aging-related submandibular gland hypofunction. Therefore, it provided a promising treatment target for aging-related dysfunction and sialadenitis of submandibular gland.
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http://dx.doi.org/10.1177/1535370221993430DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8371308PMC
June 2021

Transcriptional and morphological profiling of parvalbumin interneuron subpopulations in the mouse hippocampus.

Nat Commun 2021 01 4;12(1):108. Epub 2021 Jan 4.

Laboratory of Neural Connectivity, Brain Research Institute, Faculties of Medicine and Science, University of Zürich, Zürich, Switzerland.

The diversity reflected by >100 different neural cell types fundamentally contributes to brain function and a central idea is that neuronal identity can be inferred from genetic information. Recent large-scale transcriptomic assays seem to confirm this hypothesis, but a lack of morphological information has limited the identification of several known cell types. In this study, we used single-cell RNA-seq in morphologically identified parvalbumin interneurons (PV-INs), and studied their transcriptomic states in the morphological, physiological, and developmental domains. Overall, we find high transcriptomic similarity among PV-INs, with few genes showing divergent expression between morphologically different types. Furthermore, PV-INs show a uniform synaptic cell adhesion molecule (CAM) profile, suggesting that CAM expression in mature PV cells does not reflect wiring specificity after development. Together, our results suggest that while PV-INs differ in anatomy and in vivo activity, their continuous transcriptomic and homogenous biophysical landscapes are not predictive of these distinct identities.
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http://dx.doi.org/10.1038/s41467-020-20328-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7782706PMC
January 2021

The immunoregulatory protein B7-H3 promotes aerobic glycolysis in oral squamous carcinoma via PI3K/Akt/mTOR pathway.

J Cancer 2019 6;10(23):5770-5784. Epub 2019 Oct 6.

Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China; State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China.

OSCC (oral squamous carcinoma) is one of most common malignant cancer. Although previous studies have found abnormal expression of B7-H3 in human OSCC, the exact role and molecular mechanism of B7-H3 in OSCC remain unknown. In this study, we investigated the role of B7-H3 in glucose metabolic reprogramming of OSCC cells and . We first detected the expression of B7-H3 in OSCC samples. Next, siRNAs and overexpression short-hairpin RNA of B7-H3 were transfected into SCC25 and Cal27 cells, and cell proliferation, migration and invasion were analyzed via CCK8, colony formation and transwell assays. Then glycolysis flux was determined through measuring glucose uptake and lactate production, and mRNA and protein expression levels were determined by real-time quantitative PCR and western blot respectively. The results presented here showed B7-H3 was upregulated in OSCC samples compared with normal tissues, and the expression level was associated with tumor size and nodal metastasis. B7-H3 affects OSCC cell proliferation, migration and invasion. We also found that B7-H3 promoted the Warburg effect, evidenced by increase glucose uptake and lactate production. We further demonstrated that B7-H3 enhanced OSCC glycolysis through the upregulation of HIF-1α and its downstream targets, Glut1 and PFKFB3, which are key factors in glycolysis. Mechanically, we demonstrated that B7-H3 regulates HIF-1α expression through PI3K/Akt/mTOR pathway. Metabolic imaging of human OSCC cancer xenograft in mice confirmed that B7-H3 enhanced tumor glucose uptake, glycolysis promoted genes expression and tumor growth. Taken together, our results have unveiled a mechanism that B7-H3 drives OSCC progression through enhancing of glycolytic metabolic program in OSCC.
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http://dx.doi.org/10.7150/jca.29838DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6843865PMC
October 2019

Single-cell RNA-Seq characterization of anatomically identified OLM interneurons in different transgenic mouse lines.

Eur J Neurosci 2019 12 5;50(11):3750-3771. Epub 2019 Sep 5.

Laboratory of Neural Connectivity, Brain Research Institute, Faculties of Medicine and Natural Sciences, University of Zürich, Zürich, Switzerland.

Inhibitory GABAergic interneurons create different brain activity patterns that correlate with behavioural states. In this characterizing study, we used single-cell RNA-Seq to analyse anatomically- and electrophysiologically identified hippocampal oriens-lacunosum moleculare (OLM) interneurons. OLMs express somatostatin (Sst), generate feedback inhibition and play important roles in theta oscillations and fear encoding. Although an anatomically- and biophysically homogenous population, OLMs presumably comprise of two functionally distinct types with different developmental origins, inferred from the expression pattern of serotonin type-3a (5-HT3a, or Htr3a) receptor subunit and 5-HT excitability in a set of OLMs. To broadly characterize OLM cells, we used the Sst-Cre and the BAC transgenic Htr3a-Cre mouse lines and separately analysed SstCre-OLM and Htr3aCre-OLM types. We found a surprisingly consistent expression of Npy in OLMs, which was previously not associated with the identity of this type. Our analyses furthermore revealed uniform expression of developmental origin-related genes, including transcription factors and neurexin isoforms, without providing support for the current view that OLMs may originate from multiple neurogenic zones. Together, we found that OLMs constitute a highly homogenous transcriptomic population. Finally, our results revealed surprisingly infrequent expression of Htr3a in only ~10% of OLMs and an apparently specific expression of the 5-HT3b subunit-coding gene Htr3b in Htr3aCre-OLMs, but not in SstCre-OLMs. However, additional in situ hybridization experiments suggested that the differential expression of Htr3b may represent an unexpected consequence arising from the design of the Htr3a-Cre BAC transgenic line.
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http://dx.doi.org/10.1111/ejn.14549DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6973274PMC
December 2019

Single-Cell RNA-Seq Reveals Developmental Origins and Ontogenetic Stability of Neurexin Alternative Splicing Profiles.

Cell Rep 2019 06;27(13):3752-3759.e4

Laboratory of Neural Connectivity, Brain Research Institute, Faculties of Medicine and Natural Sciences, University of Zürich, Winterthurerstrasse 190, 8057 Zürich, Switzerland. Electronic address:

Neurexins are key synaptic organizers that are expressed in thousands of alternatively spliced isoforms. Because transsynaptic neurexin interactions with different postsynaptic molecules are largely isoform dependent, a cell type-level census of different neurexin isoforms could predict molecular interactions relating to synapse identity and function. Using single-cell transcriptomics to study the origin of neurexin diversity in multiple murine mature and embryonic cell types, we have discovered shared neurexin expression patterns in developmentally related cells. By comparing neurexin profiles in immature embryonic neurons, we show that neurexin profiles are specified during early development and remain unchanged throughout neuronal maturation. Thus, our findings reveal ontogenetic stability and provide a cell type-level census of neurexin isoform expression in the cortex.
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http://dx.doi.org/10.1016/j.celrep.2019.05.090DOI Listing
June 2019

Deep Survey of GABAergic Interneurons: Emerging Insights From Gene-Isoform Transcriptomics.

Front Mol Neurosci 2019 7;12:115. Epub 2019 May 7.

Laboratory of Neural Connectivity, Faculties of Medicine and Natural Sciences, Brain Research Institute, University of Zurich, Zurich, Switzerland.

GABAergic interneuron diversity is a key feature in the brain that helps to create different brain activity patterns and behavioral states. Cell type classification schemes-based on anatomical, physiological and molecular features-have provided us with a detailed understanding of the distinct types that constitute this diversity and their contribution to brain function. Over recent years, the utility of single-cell RNAseq has majorly complemented this existing framework, vastly expanding our knowledge base, particularly regarding molecular features. Single-cell gene-expression profiles of tens of thousands of GABAergic cells from many different types are now available. The analysis of these data has shed new lights onto previous classification principles and illuminates a path towards a deeper understanding of molecular hallmarks behind interneuron diversity. A large part of such molecular features is synapse-related. These include ion channels and receptors, as well as key synaptic organizers and trans-synaptic signaling molecules. Increasing evidence suggests that transcriptional and post-transcriptional modifications further diversify these molecules and generate cell type-specific features. Thus, unraveling the cell type-specific nature of gene-isoform expression will be a key in cell type classification. This review article discusses progress in the transcriptomic survey of interneurons and insights that have begun to manifest from isoform-level analyses.
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http://dx.doi.org/10.3389/fnmol.2019.00115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6514532PMC
May 2019

Increased cocaine self-administration in rats lacking the serotonin transporter: a role for glutamatergic signaling in the habenula.

Addict Biol 2019 11 24;24(6):1167-1178. Epub 2018 Aug 24.

Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Italy.

Serotonin (5-HT) and the habenula (Hb) contribute to motivational and emotional states such as depression and drug abuse. The dorsal raphe nucleus, where 5-HT neurons originate, and the Hb are anatomically and reciprocally interconnected. Evidence exists that 5-HT influences Hb glutamatergic transmission. Using serotonin transporter knockout (SERT ) rats, which show depression-like behavior and increased cocaine intake, we investigated the effect of SERT reduction on expression of genes involved in glutamate neurotransmission under both baseline conditions as well as after short-access or long-access cocaine (ShA and LgA, respectively) intake. In cocaine-naïve animals, SERT removal led to reduced baseline Hb mRNA levels of critical determinants of glutamate transmission, such as SLC1A2, the main glutamate transporter and N-methyl-D-aspartate (Grin1, Grin2A and Grin2B) as well as α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (Gria1 and Gria2) receptor subunits, with no changes in the scaffolding protein Dlg4. In response to ShA and LgA cocaine intake, SLC1A2 and Grin1 mRNA levels decreased in SERT rats to levels equal of those of SERT rats. Our data reveal that increased extracellular levels of 5-HT modulate glutamate neurotransmission in the Hb, serving as critical neurobiological substrate for vulnerability to cocaine addiction.
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http://dx.doi.org/10.1111/adb.12673DOI Listing
November 2019

Association between integrin-linked kinase and hyperthermia in oral squamous cell carcinoma.

Oncol Lett 2017 Dec 19;14(6):7705-7714. Epub 2017 Oct 19.

State Key Laboratory of Oral Diseases, West China College of Stomatology, Sichuan University, Chengdu, Sichuan 610041, P.R. China.

The present study aimed to observe the effect of the biological functions of integrin-linked kinase (ILK) silencing combined with hyperthermia on Tca8113 cells. Lentivirus-mediated short hairpin RNA (shRNA)-targeting ILK was transfected into oral squamous cell carcinoma (OSCC) Tca8113 cells and, combined with hyperthermia, several experimental methods were used to detect their biological behavior . On the basis of experiments, Tca8113 cells were transplanted into nude mice models, and ILK-shRNA-lentivirus was injected into the nude mice transplanted tumor and combined with hyperthermia. Tumor morphology and the associated protein expression changes were determined. Subsequent to ILK silencing combined with hyperthermia, the growth, migration and proliferation of Tca8113 cells were significantly inhibited. Flow cytometry revealed that the cells were blocked in the S phase, and western blot analysis demonstrated that ILK, phosphorylated (p)-RAC-alpha serine/threonine-protein kinase (Akt), p-glycogen synthase kinase-3β and p-heat shock factor 1 protein expression levels were significantly decreased, while apoptosis-associated protein B-cell lymphoma-2-associated X protein expression and the efficacy of hypothermia were significantly increased. By ILK silencing combined with hyperthermia, a significant therapeutic effect on transplanted tumors was observed in nude mice. Immunohistochemistry revealed the same results as the experiments. ILK silencing combined with hyperthermia can inhibit the growth, proliferation and migration of Tca8113 cells, promote Tca8113 cell apoptosis, inhibit the phosphatidylinositol-3-kinase/Akt signaling pathway and increase hyperthermia sensitivity; the combination therapy exhibits a synergistic sensitizing effect. Therefore, ILK silencing combined with hypothermia may serve as a novel combination therapy strategy against OSCC.
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http://dx.doi.org/10.3892/ol.2017.7222DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5727585PMC
December 2017

Effects of lentivirus-mediated shRNA targeting integrin-linked kinase on oral squamous cell carcinoma in vitro and in vivo.

Oncol Rep 2016 Jan 2;35(1):89-98. Epub 2015 Nov 2.

State Key Laboratory of Oral Diseases, Sichuan University, Chengdu 610041, P.R. China.

Integrin-linked kinase (ILK), a highly conserved intracellular protein of serine/threonine protein kinase activities, which is associated with the integrin and growth factor receptor signaling pathway, is involved in the regulation of cell proliferation, apoptosis, differentiation, migration and epithelial-mesenchymal transition (EMT). Findings of a previous study showed that ILK overexpression was strongly correlated with a more aggressive tumor phenotype, recurrence and poor survival for oral squamous cell carcinoma (OSCC) patients, as well as some EMT markers. In order to investigate the underlying mechanisms involved, a lentivirus-mediated short hairpin RNA (shRNA) was employed to downregulate ILK. The results showed that the knockdown of ILK inhibited cell growth, adhesion and invasion ability in vitro, and OSCC cells deficient of ILK were blocked in the S phase and underwent apoptosis. Additionally, ILK shRNA inhibited EMT by impairing the expression of Snail, Slug and Twist2 and enhacning E-cadherin expression. ILK shRNA suppressed the phosphorylation of downstream signaling targets Akt and GSk-3β. In addition, the knockdown of ILK inhibited tumor growth, invasion and metastasis of xenograft tumors in vivo. These results suggested that ILK is a promising therapeutic target for the treatment of OSCC.
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http://dx.doi.org/10.3892/or.2015.4374DOI Listing
January 2016

[Expression and clinical significance of nuclear factor κB/B cell lymphoma-2 signal pathway and glycogen synthase kinase 3β in oral squamous cell carcinoma].

Hua Xi Kou Qiang Yi Xue Za Zhi 2015 Feb;33(1):11-5

Objective: This study aims to examine the expression of nuclear factor κB (NF-κB)/B cell lymphoma-2 (Bcl-2) signal pathway and glycogen synthase kinase 3β (GSK-3β) in oral squamous cell carcinoma (OSCC) and provide references for the early diagnosis and prognosis evaluation of OSCC.

Methods: A total of 55 cases of OSCC and 10 cases of paracan- cerous mucosa were examined in this study. Their expressions of GSK-3β, NF-κB and Bcl-2 were detected using the SP me- thod immunohistochemistry. The correlation between their expression in OSCC and the clinical and pathological peculiarity of OSCC was analyzed.

Results: The positive expression of GSK-3β, NF-κB, and Bcl-2 in OSCC were significantly higher than that in paracancerous mucosa (P < 0.01). The expression of GSK-3β, NF-κB, and Bcl-2 had no obvious relationship with patient's age, sex, and clinical stages of the disease (P > 0.05). The expression of Bcl-2 was significantly correlated with the degree of tumor differentiation (P < 0.05), whereas the expression of GSK-3β and NF-κB in OSCC had no obvious relation- ship with the degree of tumor differentiation (P > 0.05). Strong positive correlations were observed among the expressions of GSK-3β, NF-κB, and Bcl-2 (P < 0.05).

Conclusion: The positive expression of GSK-3β, NF-κB, and Bcl-2 in OSCC are sig- nificantly higher than that in paracancerous mucosa. Detecting GSK-3β, NF-κB, and Bcl-2 in OSCC may have implications in the early diagnosis and prognosis evaluation of OSCC.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7030237PMC
February 2015

A hypothesis of traumatic subdural effusion associated with communicating hydrocephalus in infants and its management.

J Craniofac Surg 2015 Mar;26(2):435-7

From the *Department of Neurosurgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai; †Department of Neurosurgery, Longyan First Hospital, Fujian; and ‡Department of Neurosurgery, Pudong Hospital, Shanghai, China.

We report a case with both traumatic subdural effusion (TSE) and associated hydrocephalus. A collapse of the sinuses is known to be present in some infants with external hydrocephalus, but collapsed sinuses have not been previously described in patients with TSE and associated hydrocephalus. Therefore, a preoperative magnetic resonance imaging venography was performed, with thrombosis in the left transverse and sigmoid sinuses identified. The infant was treated with subdural peritoneostomy. We hypothesized that an occlusive cerebral venous sinus thrombosis may well be the culprit, or an exacerbating factor for TSE associated with hydrocephalus.
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http://dx.doi.org/10.1097/SCS.0000000000001329DOI Listing
March 2015

In vitro cytotoxicity and in vivo acute and chronic toxicity of Xanthii Fructus and its processed product.

Biomed Res Int 2013 26;2013:403491. Epub 2013 Nov 26.

Yunnan University of Traditional Chinese Medicine, Kunming, Yunnan 650500, China.

Xanthii Fructus (XF), the fruit of Xanthium sibiricum Patr., was used in the treatment of rhinitis and related nasal disease. Adverse effects of Xanthii Fructus are frequently reported these years. In the paper, in vitro renal cytotoxicity and in vivo acute and chronic toxicity researches of Xanthii Fructus (XF) and its processed product (processed Xanthii Fructus (PXF)) were carried out. Water extraction of XF displayed no cell membrane damage effects even in the highest concentration (100 μg/mL); however, it might affect the function of renal cell mitochondria. Acute toxicities were observed only in high and middle dosage groups. Fortunately, the single dose administration of XF or PXF was safe even at the highest daily dosage. Twelve-week chronic toxicity assays were performed in SD rats with low, middle, and high dosage. Notable changes in body weight and blood cell and BUN and Scr changes sporadically occurred in middle and high groups after the 9th week. Serum HA and HPCIII values were sustained increasing from the 4th week to the 8th week in Group V male rats, which indicated that the renal fibrosis risks still existed although no fibrosis was found in the pathological examination of the liver and kidney.
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http://dx.doi.org/10.1155/2013/403491DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3858965PMC
August 2014

Hypoxia-inducible factor-1α overexpression indicates poor clinical outcomes in tongue squamous cell carcinoma.

Exp Ther Med 2013 Jan 30;5(1):112-118. Epub 2012 Oct 30.

Department of Oral and Maxillofacial Surgery, Hospital of Stomatology, Tongji University, Shanghai 200072;

The aim of the present study was to investigate the expression of hypoxia-inducible factor-1α (HIF-1α) in tongue squamous cell carcinoma (TSCC) and to assess its possible impact on prognosis. A total of 49 tumor samples and 15 adjacent non-tumor samples from 49 patients treated between January 2000 and December 2005 at the Department of Oral and Maxillofacial Surgery, Hospital of Stomatology, Tongji University (Shanghai, China) were obtained for investigation with immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR). The expression of HIF-1α was detected in 87.76% (43/49) of the TSCC samples and in 33.33% (5/15) of the adjacent non-tumor tissues. The expression of vascular endothelial growth factor (VEGF) was also observed in 83.67% (41/49) of the TSCC samples and in only 20% (3/15) of the adjacent non-tumor samples at a low level. RT-PCR revealed that the mRNA expression of HIF-1α and VEGF was present in the tumor tissues; however, it was barely detected in the corresponding adjacent normal tissues. The overexpression of HIF-1α was significantly associated with T classification (P=0.01), lymphatic metastasis (P=0.05) and histological differentiation (P<0.001). Furthermore, HIF-1α overexpression was significantly associated with poor overall (P=0.001) and disease-free survival rates (P=0.01), independent of T stage and lymphatic metastasis. The Cox proportional hazards regression model demonstrated that the level of HIF-1α expression may be an independent prognostic factor for TSCC. HIF-1α overexpression was observed in TSCC and its overexpression suggests a poor prognosis. HIF-1α may be a molecular marker for predicting the prognosis of TSCC.
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http://dx.doi.org/10.3892/etm.2012.779DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3524283PMC
January 2013

Effects of trichostatin A on HIF-1α and VEGF expression in human tongue squamous cell carcinoma cells in vitro.

Oncol Rep 2012 Jul 23;28(1):193-9. Epub 2012 Apr 23.

Department of Oral and Maxillofacial Surgery, Hospital of Stomatology, Tongji University, Shanghai 200072, PR China.

Hypoxia is an essential feature of the microenvironment of solid tumors, which regulates a variety of transcription factors including hypoxia-inducible factor-1α (HIF-1α). HIF-1α overexpression enhances tumor angiogenesis via upregulation of vascular endothelial growth factor (VEGF) and some other hypoxia-inducible angiogenic factors, which lead to a more aggressive tumor phenotype, tumor metastasis and resistance to radiation and chemotherapy. In this study, we found that a histone deacetylase (HDAC) inhibitor, trichostatin A (TSA), inhibited cell proliferation and invasion, blocked the cell cycle, and induced cell apoptosis in a dose- and time-dependent manner in the human tongue squamous cell carcinoma (TSCC) SCC-6 cell line in vitro. Furthermore, TSA reduced both basal levels and hypoxia-induced HIF-1α protein accumulation but not HIF-1α mRNA levels, and both protein and mRNA levels of VEGF expression. These results showed that TSA had a potent anticancer activity on TSCC cells, suggesting that TSA could be a promising drug targeting tumor angiogenesis via inhibition of HIF-1α and VEGF expression in the development of an effective chemopreventive and anticancer agent on human TSCCs.
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http://dx.doi.org/10.3892/or.2012.1784DOI Listing
July 2012
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