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IFIX, a newly discovered member of the interferon-inducible HIN-200 family, has been identified as a tumor suppressor in breast cancer; however, the involvement of IFIX in oral cancer are poorly understood. Here, we demonstrate a relationship between the level of IFIX expression and the invasive or migratory abilities of oral squamous cell carcinoma. Higher IFIX expression significantly correlated with clinicopathological parameters such as the histopathological grade of clinical samples. In vitro, IFIX overexpression suppressed the invasiveness of human tongue squamous cell carcinoma CAL-27 cells, and this inhibitory effect was mediated by stabilization of the cytoskeleton through various cytokeratins along with downregulation of paxillin, an intracellular adaptor protein that promotes tumor invasion. This inhibitory effect does not appear to affect the transformation of cancer stem-like cells in this cell culture model. Altogether, these data provide novel insights into the tumor-suppressive function of IFIX, namely, stabilization of the cancer cell cytoskeleton.

BACKGROUND: Resistance to PD-1 blocking agents is not uncommon, limiting their wide clinical success. Certain tumor-infiltrating immune cells (e.g., TILs/CTLs) have emerged as biomarkers of response, and absence of such immune cells contributes to resistance. OBJECTIVE: We deconvoluted the dynamic immune microenvironment in a mouse model of oral carcinogenesis for augmenting the resistance to PD-1 blocking agents by combination. METHODS: Bioinformatics methods and routine biological experiments were adopted such as morphological analysis and ELISA in the 4NQO-treated mice model. RESULTS: Our findings revealed that dysplastic tongue tissues from 4NQO-treated mice were characterized by an immunosuppressive tumor microenvironment. Tongue tissues from mice treated with 4NQO for 12 weeks had higher levels of Th2 cells and Tregs compared to tissues taken from control mice or mice treated with 4NQO for 28 weeks; these results suggested a potential therapeutic benefit of anti-PD-1 in the oral cancer. The IL-17 pathway was significantly upregulated during progression from normal mucosa to hyperplasia and tumor formation in mice. Inhibition of IL-17α combined with PD-1 blockade delayed the development of 4NQO-induced precancerous and cancerous lesions and prolonged the survival of 4NQO-treated mice. CONCLUSIONS: Our data suggested a strong rationale of IL-17α blockade as a potential approach to augment the tumor-eliminating effects of anti-PD-1 therapy.

Background Colleges and universities in China have offered courses based on online teaching platforms as required by the Ministry of Education since the beginning of the COVID-19 pandemic. This emergency action was not an expedient measure, but a powerful impetus to improve extant education and implement teaching reform. Oral histopathology is a basic subject in oral medicine education, which combines theory with practice. The course aims to improve the ability of students to observe, think, analyze and identify oral diseases. Method We adjusted and modified the original Bridge-In, Outcomes, Pre-assessment, Participatory Learning, Post-assessment, and Summary (BOPPPS) teaching method to fit the characteristics and needs of oral histopathology. We then combined the characteristics of Small Private Online Courses (SPOCs) and a Flipped class to complete teaching material online, and assessed the effects of such teaching using a questionnaire and interviews. Fifty 5th-year undergraduates in stomatology at the School of Stomatology of Harbin Medical University of China participated in online classes. All were in the junior second half of the semester at the beginning of 2020. Teachers investigated from various medical colleges were responsible for delivering courses associated with stomatology or ophthalmology. Result & conclusion The results showed that the modified BOPPPS combined with SPOC and the Flipped class improved teaching satisfaction. Modified BOPPPS combined with SPOC and the Flipped class is a useful complement to offline teaching on 5th-year undergraduate oral histopathology learning in China during COVID-19, and it can meet the multiple needs of students participating in the course.

PIWIL2 is a human Argonaute protein, which is guided by small RNAs to its targets, plays a role in germ cell maintenance and has been proposed to be expressed in precancerous stem cells and tumor stem cells. However, the significance of PIWIL2 expression in oral cancer and precancerous lesions has not been investigated. In this study, we analyzed the expression of the stem cell protein PIWIL2 in oral squamous-cell carcinoma (OSCC) and in premalignant oral leukoplakia (OL) with predominant expression in malignant and premalignant tissues. In the evaluated patients, we found that PIWIL2 was associated significantly with OSCC prognosis and OL. Furthermore, PIWIL2 was found to be expressed in tumor epithelial cells and macrophages in the tumor microenvironment, which are not derived from enlarged lymph nodes. Cytological experiments confirmed that the human squamous cell carcinoma cell line SCC-25, can promote the PIWIL2 and Nanog level in THP-1 cells, which are extensively used to study the modulation of monocytes and macrophages. Our findings showed that PIWIL2 can predict effectively OSCC prognosis and OL with a high risk of OSCC development and substantiate the deduction that cancer stem(-like) cells in oral cancer have the ability to reconstitute the heterogeneity of the bulk tumor and contribute to poor outcome and immunosuppression.

Due to the air holes in cladding, it is difficult to process for end faces of ytterbium-doped double-cladding microstructured optical fibers. In this paper, we demonstrate the fabricating method of microlenses on ytterbium-doped double-cladding microstructured optical fibers with a CO2 laser to enhance the coupling efficiency. The theoretical and experimental investigation is carried out to study the effect of minor axis semidiameter and major axis semidiameter of ellipsoidal microlenses on coupling efficiency. The coupling efficiency is up to 88%, which is 14.6% higher than that of the perpendicular flat-end microstructured optical fiber using a free space optical path. These results suggest that the proposed end face processing on microstructured optical fibers provides a straightforward solution for the production of microlenses for laser coupling applications in high-power fiber lasers.

Objective To observe the relationship of rheumatoid arthritis (RA) bone destruction with T cells, regulatory T cells (Tregs), CD19

Background This study aimed to evaluate the relationship between survivin expression and melanoma after 5-aminolevulinic acid (5-ALA)-mediated sonodynamic therapy. Methods Immunohistochemistry was used to detect survivin protein expression in human melanoma clinical samples. Subsequently, the effects of 5-ALA-mediated sonodynamic therapy were determined by measuring the volume of melanoma xenografts and the bodyweights of melanoma-bearing nude mice. The MTT assay was used to detect the viability of melanoma B16-F10 cells under the action of 5-ALA-mediated sonodynamic therapy, and Western blotting and PCR were used to detect survivin expression in melanoma cells and in the melanoma-xenograft model. Results Survivin expression was significantly upregulated in human melanoma tissues compared with that of non-melanoma tissues. In the in vivo case, 5-ALA-mediated sonodynamic therapy significantly delayed tumor growth, prolonged the survival of mice, and inhibited the expression of survivin. In the in vitro case, 5-ALA-mediated sonodynamic therapy inhibited B16-F10 cell proliferation and decreased survivin expression at both protein and mRNA levels. Conclusion Our results suggest that 5-ALA-mediated sonodynamic therapy inhibited B16-F10 cell proliferation and melanoma-xenograft growth and prolonged survival of melanoma-bearing nude mice, which might be through downregulation of survivin expression.

Objective: The aim of this study was to characterize clinical features, etiologies, and mechanisms of strokes due to bilateral middle cerebellar peduncle infarction (BMCPI). Methods: Cases diagnosed as BMCPI in our hospital were retrieved, and a literature review was performed. Data on clinical features and brain MRI were obtained. Extracranial and intracranial segments of the vertebrobasilar artery were assessed by using digital subtraction angiography, magnetic resonance angiography, or computed tomography angiography. Results: Thirteen cases (11 men and 2 women) of BMCPI were identified. A high-intensity signal of diffusion-weighted imaging sequence involving the bilateral middle cerebellar peduncle was observed in all patients. Most patients experienced vertigo, dysarthria, ataxia, and hearing disorders. Eleven of these cases were classified as large artery atherosclerosis, one as traumatic vertebral artery (VA) dissection, and one as giant cell arteritis. Conclusion: BMCPI is a rare cerebrovascular disease characterized by vertigo, ataxia, and dysarthria, which may also be accompanied by a hearing deficit or clinical signs of brainstem damage. BMCPI may be associated with hypoperfusion secondary to occlusive disease of the bilateral VA or proximal basilar artery.

Faster R-CNN algorithm is a deep learning network model based on regional suggestion network, which is applied to the field of target detection and recognition. Extracting a small number of pixels in the original image and generating a downscaled image can improve the detection efficiency of Faster R-CNN. Scene semantic narrowing is be directed at specific types of regions and geographical locations in the image. By performing targeted analysis on these regions, it can be interpreted more carefully, and the image is better applied to Faster R-CNN. The deep convolutional network with the narrowing function of the theme is studied. The main factors that affect the understanding of image content accumulated by human visual cognitive experience and computer vision research are summarized into various themes, and the appropriate theme is selected as a narrow sub-network according to the task. Realize the optimization of the Faster R-CNN algorithm by implementing a collaborative deep network with clear functions in the overall black box and subnet. The experimental results show that the proposed method can significantly shorten the detection time of the algorithm while improving the detection accuracy of Faster R-CNN algorithm.

Introduction Wernicke's encephalopathy (WE) is a severe neuropsychiatric disorder, which results from a nutritional deficiency of thiamine. The occurrence of WE is rarely reported in patients with cerebral infarction, who often have complications of malnutrition. Cerebral infarction is a neurological disease, patients with cerebral infarction may show symptoms such as disturbance of consciousness and gait instability, which is difficult to differentiate from WE. Thus, early recognition and differential diagnosis of WE are important. We report a rare case of cerebral infarction patient who developed WE due to malnutrition and parenteral nutrition. Patient concerns A 65-year-old woman was admitted to our hospital with cerebral infarction. She had lost 15 kg of weight in the past month or so and was diagnosed with malnutrition. In order to correct malnutrition, parenteral nutrition and intravenous glucose without thiamine were administered. Cognitive dysfunction, laloplegia, sleep rhythm inversion, somnolence and bilateral lower limbs weakness were presented 20 days after admission. Diagnosis Brain magnetic resonance imaging confirmed the diagnosis of WE. Interventions The patient was given thiamine and nutrition support therapy. Outcomes The patient's cognitive impairment, laloplegia and sleep condition improved within 4 days. Neurological status continued to improve and physical activity recovered gradually within 2 weeks. She received rehabilitation training when her condition was relatively stable, and her muscle strength of limbs and physical function gradually improved. Conclusion Infarction-related malnutrition may result in nutrient deficiency-related neurological complications, such as WE. Thus, it is important to pay close attention to the nutritional status of patients with cerebral infarction. In addition, early recognition and differential diagnosis of WE in patients with infarction-related malnutrition are necessary, early treatment of replete thiamine supplementation and nutrition support therapy can reduce the risk of WE and improve the prognosis.

We report optical properties and fabrication of hollow core fibers in our lab for optical pumped fiber gas laser. A width transmission window in near infrared spectral region is obtained in octagram hollow core fiber.

We investigate the temporal evolution of photodarkening effect in ytterbium-doped large-mode-area photonic crystal fiber and discuss its mechanism. The results show the great influence of photodarkening on lasing properties.

Background Oral squamous cell carcinoma (OSCC) invades surrounding tissues by upregulating matrix metalloproteinases (MMPs) -2 and −9, which causes over-expression of the Hedgehog signaling proteins Shh and Gli-1 and degradation of the extracellular matrix, thereby creating a “highway” for tumor invasion. We explored the potential of low intensity ultrasound (LIUS) and doxorubicin (DOX) to inhibit the formation of this “highway”. Methods MTT assays were used to examine OSCC cell viability after exposure to LIUS and DOX. The cell morphological changes and ultrastructure were detected by scanning electron microscopy and transmission electron microscopy. Endogenous autophagy-associated proteins were analyzed by immunofluorescent staining and western blotting. Cell migration and invasion abilities were evaluated by Transwell assays. Collagen fiber changes were evaluated by Masson’s trichrome staining. Invasion-associated proteins were analyzed by immunohistochemistry and western blotting. Results LIUS of 1 W/cm2 increased the in vitro DOX uptake into OSCC by nearly 3-fold in three different cell lines and induced transient autophagic vacuoles on the cell surface. The combination of LIUS and 0.2 μg/ml DOX inhibited tumor cell viability and invasion, promoted tumor stromal collagen deposition, and prolonged the survival of mice. This combination also down-regulated MMP-2, MMP-9, Shh and Gli-1 in tumor xenografts. Collagen fiber expression was negatively correlated with the expression of these proteins in human OSCC samples. Conclusions Our findings suggest that effective low dosages of DOX in combination with LIUS can inhibit cell proliferation, migration and invasion, which might be through MMP-2/9 production mediated by the Hedgehog signaling pathway. Electronic supplementary material The online version of this article (10.1186/s13046-017-0633-y) contains supplementary material, which is available to authorized users.

In the present study, the presence of extracellular matrix components, including collagenous and elastic fibers, and the expression of their key regulating enzymes, were investigated in different stages of hamster tongue carcinoma development. Immunohistochemical and computer-assisted morphological analyses were performed to quantify the staining intensity and area (integral optical density) of matrix metalloproteinase (MMP)-1 and -2, tissue inhibitors of metalloproteinase (TIMP)-1 and -2, and the extent of elastic and collagenous fibers in histological sections. MMP-1, MMP-2, TIMP-1 and TIMP-2 expression levels gradually increased with tongue cancer progression, and were associated with disease pathology staging (r=0.705, 0.633, 0.759 and 0.751, respectively). By contrast, elastic fiber levels gradually decreased with cancer progression and were negatively correlated with disease staging (r=-0.881). The levels of collagenous fibers gradually increased with cancer progression and showed a positive correlation (r=0.619). In summary, the study demonstrated that MMP1/2 and TIMP1/2 expression levels, and collagenous and elastic fiber levels were significantly correlated with disease progression in a hamster model of tongue cancer.

Background Neuropilin-2 (NRP2), a receptor for vascular endothelial growth factor C (VEGF-C) and semaphorin 3 F (SEMA3F), is a possible regulator of tumor progression and angiogenesis. However, little evidence of a correlation between NRP2 expression and lymphangiogenesis has been reported. SEMA3F might suppress lymphangiogenesis by competing with VEGF-C for binding to NRP2. Methods We evaluated lymphatic vessel density (LVD), lymphatic vessel invasion (LVI), the expression levels of VEGF-C, SEMA3F, and NRP2 by immunohistochemistry in 80 cases of oral squamous cell carcinomas (OSCCs). Results In these tumors, the expression of NRP2 was positively associated with T stage classification, lymph node metastasis, LVD, LVI, and the expression of VEGF-C. In contrast, low expression of SEMA3F was significantly related to poor differentiation and higher incidence of lymph node metastasis. Patients expressing high levels of VEGF-C or NRP2, or low levels of SEMA3F had a higher risk of recurrence and shorter overall survival. Multivariate analysis showed that VEGF-C and NRP2 were independent prognostic markers for overall survival. Conclusions Results indicate SEMA3F is an inhibitor of tumor progression and provide evidence for an association between NRP2 and VEGF-C, lymphangiogenesis, lymph node metastasis. This suggests the prognostic significance and potential therapeutic value of the VEGF-C/SEMA3F/NRP2 axis for OSCCs. J. Surg. Oncol. 2015 111:382–388. © 2014 Wiley Periodicals, Inc.

The cruciferous herb Weixian radish (Raphanus sativus L.), also known as Lai Fu, is a popular type of edible vegetable. The present paper describes the molecular tracking and bioactivity of glucocerebroside isolated from Weixian radish for the first time. Methanol extraction was carried out by using silica gel, Sephadex LH-20 and RP-C18 column chromatography. Based on their structures, the two compounds were determined to be 1-O-(β-D-glucopyranosyl)-(2S, 3S, 4R, 8E)-2-[(2'R)-2'-hydroxyl-tetracos-15'-enoyl amino]-8-octa-decene- 1, 3, 4-triol (glucocerebroside). The glucocerebroside could inhibit the growth of BEL-7402 cancer cells and induce apoptosis in these cells.

The objective of this study was to explore the prognostic value of cancer stem cell markers, namely CD133, NANOG, and NOTCH1, in early stage oral squamous cell carcinoma (OSCC). One hundred forty-four patients with early stage (cT1T2N0) OSCC were identified from a pre-existing database of patients with oral cancer. We examined the impact of the immunohistochemical expression of CD133, NANOG, and NOTCH1 in OSCC. Overall survival (OS) curves were calculated using the Kaplan–Meier method. Predictors of outcome were identified using multivariate analysis. We found that CD133, NANOG, and NOTCH1 were significantly associated with lymph node metastasis, and NOTCH1 was also significantly associated with depth of invasion and locoregional recurrence. NOTCH1 was identified as an independent prognostic factor for OS. NOTCH1 might prove to be a useful indicator for high-risk patients with occult metastases from early stage OSCC.

Figure S1. Schematic diagram of the low-intensity ultrasound device and experimental setup. Figure S2. Schematic diagrams of ultrasound pressure level distribution for in vitro and in vivo experiments. Figure S3. The effects of LIUS and DOX on HT293 cell. (PPT 734 kb)

Let μ be a normal function on [0,1). The atomic decomposition of the μ-Bergman space in the unit ball B is given for all p > 0.

A rapid, environmental friendly, and sensitive biosensor for detection of zearalenone (ZEN) was developed at glassy carbon electrode (GCE) using nanoporous bimetallic alloy as label of secondary antibody (Ab2). The biosensor was prepared by immobilizing nitrogen-doped graphene sheets (N-GS) captured primary antibody (Ab1) on GCE. The analytes were then bound to Ab1 for further capture of antibodies, labeled by the nanoporous bimetallic alloy, nanoporous PtCo alloy (NP-PtCo). NP-PtCo with three-dimensional bicontinuous spongy structures and various hollow channels was prepared by corrosion of PtCoAl alloy, and exhibited remarkably improved electrocatalytic activity toward H2O2. Within ZEN concentration range (0.005–25 ng mL−1), the biosensor exhibited a highly sensitive response to ZEN with a detection limit of 2.1 pg mL−1. Several factors that would affect the performance of the biosensor were studied, such as erosion time of NP-PtCo, concentration of NP-PtCo, pH of buffer solution, and concentration of N-GS. After H2O2 was injected into the buffer solution, the amperometric response of the biosensor can be used to detect ZEN by chronoamperometry. The developed biosensor shows good selectivity and sensitivity to ZEN and is promising in feed safety analysis.

In this contribution, mesoporous carbon nanospheres (MCN) were used to fabricate a label-free electrochemical immunosensor for breast cancer susceptibility gene (BRCAl). The detection platform was constructed by conjugation of anti-BRCA1 on glassy carbon electrodes which were modified by mesoporous carbon nanospheres–toluidine blue nanocomposite (MCN–TB)/room temperature ionic-liquid (RTIL) composited film. TB was adsorbed onto MCN and acted as a redox probe. The electroactivity of TB was greatly enhanced in the presence of MCN. The good conductivity of MCN and BMIM·BF4 could promote the electron transfer and thus enhance the detection sensitivity. Moreover, the large surface area of MCN and the protein-binding properties of BMIM·BF4 could greatly increase the antibody loading. The specific antibody–antigen immunoreaction on the electrode surface resulted in a decrease of amperometric signal of the electrode. Under optimized conditions, the amperometric signal decreased linearly with BRCAl concentration in the range of 0.01–15 ng mL−1 with a low detection limit of 3.97 pg mL−1. The immunosensor exhibits high sensitivity, good selectivity and stability.

Bisphenol A (BPA), which could disrupt endocrine system and cause cancer, has been considered as an endocrine disruptor. Therefore, it is very important and necessary to develop a sensitive and selective method for detection of BPA. Herein, nitrogen-doped graphene sheets (N-GS) and chitosan (CS) were used to prepare electrochemical BPA sensor. Compared with graphene, N-GS has favorable electron transfer ability and electrocatalytic property, which could enhance the response signal towards BPA. CS also exhibits excellent film forming ability and improves the electrochemical behavior of N-GS modified electrode. The sensor exhibits a sensitive response to BPA in the range of 1.0 × 10−8–1.3 × 10−6 mol L−1 with a low detection limit of 5.0 × 10−9 mol L−1 under the optimal conditions. Finally, this proposed sensor was successfully employed to determine BPA in water samples with satisfactory results.

Hai-Xia Fan,1 Yan Chen,1 Bo-Xiong Ni,1 Shan Wang,1 Miao Sun,2 Dong Chen,2 Jin-Hua Zheng11Department of Anatomy, Basic Medical Science College, 2Department of Oral and Maxillofacial Surgery, Stomatological Hospital, Harbin Medical University, Harbin, People’s Republic of ChinaBackground: Matrix metalloproteinase (MMP)-1 degrades type I collagen of the extracellular matrix and also activates protease activated receptor (PAR)-1 to induce angiogenesis. The aims of this study were to evaluate microvessel density (MVD) and the expression of PAR-1 and MMP-1 in oral squamous cell carcinoma (SCC) specimens with different patterns of invasion (POI) and to evaluate their association with clinical outcomes.Methods: Seventy-four surgically obtained oral SCC samples were classified by POI according to hematoxylin-eosin staining. MVD and the localization and intensity of PAR-1 and MMP-1 expression were detected by immunohistochemistry.Results: Of the 74 oral SCC samples, 18, 5, 34, and 17 showed type I, II, III, and IV POI, respectively. MVD and expression levels of MMP-1 and PAR-1 differed between POI types I–II and POI types III–IV. Patients with low tumor expression of MMP-1 and PAR-1 and low MVD had a longer survival time than those with high tumor expression of MMP-1 and PAR-1. Moreover, the survival time of patients with POI types III–IV was shorter than that of patients with POI types I–II.Conclusion: POI combined with expression levels of MMP-1 and PAR-1 may be a valuable tool for assessing the clinical prognosis of patients with oral SCC.Keywords: oral squamous cell carcinoma, pattern of invasion, immunohistochemistry, clinical outcomes

Backgroud Malignant melanoma is a very refractory skin tumor due to its high metastasis, poor prognosis, and insensitivity to chemotherapy. Sonodynamic therapy has recently evolved as a potential method to treat cancers. In this study, 5-aminolevulinic acid-mediated sonodynamic therapy (ALA-SDT) was used to treat malignant melanoma in vivo . Objective To investigate whether ALA-SDT induces anti-tumor effects in malignant melanoma and to see if miRNAs are involved in this process. Methods Tumor transplantation experiments in BALB/c nude mice were used to assess anti-tumor effects after ALA-SDT treatment. Cell apoptosis was evaluated by TUNEL assays and cell proliferation was measured using immunohistochemisty with anti-PCNA antibody. Microarray analysis was performed to measure miRNAs expressions. Endogenous miR-34a and its upstream and downstream genes were assayed by real-time PCR. Western blottings were used to determine these protein expressions. Intracellular ROS levels were detected by measuring the fluorescence intensity of DCF. Results Tumor transplantation experiments revealed that ALA-SDT could inhibit mouse melanoma cell proliferation and tumor growth. Compared with the control group, TUNEL assays revealed that apoptosis was increased and proliferation was inhibited in the SDT group. Real-time PCR analysis showed 14-fold increase of miR-34a expression in the SDT group compared to the control group. In addition, ALA-SDT significantly increased intracellular ROS levels in vitro , which were almost inhibited by the ROS scavenger NAC. Also, the mRNA, total protein, and acetylation levels of p53 were increased, whereas some downstream anti-apoptotic or pro-proliferative factors of miR-34a such as BCL2, CCND1, CDK6, and SIRT1 were decreased in the SDT group compared with the control, ALA alone, and ultrasound alone groups. When miR-34a was inhibited in vitro , the protein expressions of BCL2, CCND1, CDK6, and SIRT1 recovered. By targeting SIRT1, which inhibits p53 acetylation, miR-34a promoted the transcriptional activity of p53, and finally led to increased expression of miR-34a itself. Therefore, the p53, miR-34a, and SIRT1 constituted a positive feedback loop. Conclusion ALA-SDT showed synergistic anti-tumor effects in malignant melanoma by constituting a positive feedback loop of p53-miR-34a-Sirt1 axis.

Bioactivity-guided study led to the isolation of a natural phenylpropionate derivative, (E)-3-(4-hydroxy-2-methoxyphenyl)-propenoic acid 4-hydroxy-3-methoxyphenyl ester from the roots of Mirabilis himalaica. Cellular analysis showed that compound 1 specifically inhibited the cancer cell growth through the S phase arrest. Mechanistically, compound 1 was able to induce the apoptosis in HepG2 cells through mitochondrial apoptosis pathway in which Bcl-2 and p53 were required. Interestingly, the cellular phenotype of compound 1 were shown specifically in cancer cells originated from hepatocellular carcinoma (HepG2) while compromised influence by compound 1 were detected within the normal human liver cells (L-02). Consistently, the in vivo inhibitory effects of compound 1 on tumor growth were validated by the in xenograft administrated with HepG2 cells. Our results provided a novel compound which might serve as a promising candidate and shed light on the therapy of the hepatocellular carcinoma.

The aim of this study was to investigate sonic hedgehog (SHH) signaling pathway components (Shh and Gli-1), E-cadherin, and MMP-9 expression in human oral squamous cell carcinoma (OSCC) and to evaluate their role in prognosis. Expression of Shh, Gli-1, and MMP-9 was significantly upregulated in 74 OSCC samples compared with non-cancerous tissue samples (Shh IOD: 162.44 ± 29.35 and 608.82 ± 170.99; Gli-1 IOD: 203.50 ± 71.57 and 831.11 ± 242.352; MMP-9 IOD: 196.69 ± 64.48 and 721.64 ± 197.99 in non-cancerous and tumor tissues, respectively, P

A sandwich electrochemical immunosensor is described for carbohydrate antigen 72-4 (CA72-4) based on a dual amplification strategy with nanoporous gold (NPG) film as the sensor platform and polyaniline-Au asymmetric multicomponent nanoparticles (PANi-Au AMNPs) as labels. In this study, the second anti-CA72-4 antibody (Ab2) adsorbed onto the Au of the PANi-Au AMNPs, which could be simply synthesized by interfacial reaction and have many characteristics of polyaniline and Au nanoparticle, such as well-controlled size, high conductivity, biocompatibility and catalysis. NPG film was used as electrode substrate material to fix a large number of antibodies, due to its unique properties: good biocompatibility, high conductivity, large surface area, and stability. The synergetic of NPG film and PANi-Au AMNPs could increase signal response, and significantly improve sensitivity of the immunosensor. The proposed immunosensor exhibited a wide linear range from 2 to 200 U/mL, with a detection limit of 0.10 U/mL CA72-4, good reproducibility, selectivity and stability. This new type of labels for immunosensors may provide many potential applications in the detection of carbohydrate antigen in immunoassays.

Ethnopharmacological relevance The roots of Mirabilis himalaica have been used in Tibetan folk medicine for treatment of uterine cancer, nephritis edematous, renal calculus and arthrodynia. In our previous work, the ethanol extract of roots had shown potent cytotoxicity against human cancer cells. However, no information is available on the antitumor effect of Mirabilis himalaica. The aim of the present study was to investigate the active constituents guided by bioassay and evaluate the related antitumor efficacy in vitro and in vivo . Materials and methods The active subextract (ethyl acetate) was subjected to successive chemical separation using a combination of silica gel, LH-20 chromatography and semi-preparative HPLC. The structures were determined by spectroscopic analysis techniques such as nuclear magnetic resonance (NMR) and mass spectrometry. Three human cancer cell lines, A549, HepG2 and HeLa were used for in vitro cytotoxicity evaluation of all isolated compounds by MTT-assay. Then, the potent and novel compound mirabijalone E was employed to the mechanism study againstA549 cells. BrdU immunofluorescence, soft agar assay and cell cycle analysis were employed to detect the cell proliferation effects. Annexin V-FITC/PI staining assay was used for examining apoptotic effects. Expression levels of apoptosis-related proteins were determined by western blot assay. in vivo tumorigenic assay was used to evaluate the xenograft tumor growth treated with mirabijalone E. Results One new rotenoid compound, mirabijalone E, together with eight known rotenoids was isolated from Mirabilis himalaica . Mirabijalone E, 9- O -methyl-inone B, boeravinone C and boeravinone H exhibited cytotoxicity against A 549 and HeLa cells. Further study on mirabijalone E was carried out in vitro and in vivo . Mirabijalone E inhibited A549 cells growth in a time and dose-dependent manner, which arrested cell cycle in S phase. Mechanistically, mirabijalone E treatment resulted in the increase of Bax expression level, the decrease of Bcl-2 level and the activation of caspase-3, which suggested the activation of apoptosis cascades. Consequently, the xenograft treated with mirabijalone E showed markedly suppressed tumor growth. Conclusions The result suggested that mirabijalone E, together with active compounds, 9- O -methyl-4-hydroxyboeravinone B, boeravinone C and boeravinone H could be a promising candidate for cancer therapy.

Neuropilin-2 (NRP2), a receptor for vascular endothelial growth factor C (VEGF-C) and semaphorin 3 F (SEMA3F), is a possible regulator of tumor progression and angiogenesis. However, little evidence of a correlation between NRP2 expression and lymphangiogenesis has been reported. SEMA3F might suppress lymphangiogenesis by competing with VEGF-C for binding to NRP2.We evaluated lymphatic vessel density (LVD), lymphatic vessel invasion (LVI), the expression levels of VEGF-C, SEMA3F, and NRP2 by immunohistochemistry in 80 cases of oral squamous cell carcinomas (OSCCs).In these tumors, the expression of NRP2 was positively associated with T stage classification, lymph node metastasis, LVD, LVI, and the expression of VEGF-C. In contrast, low expression of SEMA3F was significantly related to poor differentiation and higher incidence of lymph node metastasis. Patients expressing high levels of VEGF-C or NRP2, or low levels of SEMA3F had a higher risk of recurrence and shorter overall survival. Multivariate analysis showed that VEGF-C and NRP2 were independent prognostic markers for overall survival.Results indicate SEMA3F is an inhibitor of tumor progression and provide evidence for an association between NRP2 and VEGF-C, lymphangiogenesis, lymph node metastasis. This suggests the prognostic significance and potential therapeutic value of the VEGF-C/SEMA3F/NRP2 axis for OSCCs.

To investigate the effects of Xinfeng Capsule (XFC) on pulmonary function and related mechanism in adjuvant-induced arthritis (AA) rats.The rats were randomly divided into five groups: normal control (NC), model control (MC) groups, methotrexate (MTX), tripterygium glycosides tablet (TPT) and Xinfeng capsule (XFC) treatment groups. The adjuvant-induced arthritis model was established by intracutaneous injection of 0.1 mL Freund ' s complete adjuvant in the right paw of rats; the drugs were given 19 d after model establishment. The toe swelling degree (E), arthritis index (AI), pulmonary function, peripheral blood Treg levels, pathological changes of lung tissue and expression of Foxp3, TGF-β1, Smad3, Smad7 proteins in lung tissue were measured 30 d after drug administration.Compared to NC group, the levels of E, AI, alveolitis score, TGF-β1 and Smad3 were significantly increased (P0.05 or P0.01); maximum expiratory flow 25% of vital capacity (FEF25),50% maximal expiratory vital capacity flow (FEF50), maximum expiratory flow at 75% of vital capacity (FEF75), maximum mid-expiratory flow (MMF), force peak expiratory flow (PEF), CD4+ CD25+ Treg, Foxp3 and Smad7 were significantly decreased in MC group (P0.05 or P0.01). Compared to MC group,the expression of E, AI, TGF-β1 and Smad3 were reduced, while FEF50, FEF75, MMF, PEF, Treg, Foxp3 and Smad7 were elevated in XFC group (P0.05 or P0.01). Compared to XFC group, the level of body mass,FEF25,FEF50, FEF75, MMF and Treg were lower in MTX and TPT groups (P0.05 or P0.01).There are inflamed joints and reduced pulmonary function in rats of adjuvant-induced arthritis. XFC can inhibit paw edema degrees, reduce arthritis response, and improve pulmonary function, which is associated with up-regulating expression of Treg and Foxp3, down-regulating the expression of TGF-β1 and adjusting TGF-β1/Smads signal pathway.

Objective To observe the impact of xinfeng xapsule (XFC) on pulmonary function in a rat model of adjuvant arthritis (AA) and to investigate the mechanism of action. Methods Forty rats were randomly divided into four groups of ten: normal control (NC); model control (MC); tripterygium glycosides tablet (TPT); and xinfeng capsule (XFC). Except for the NC group, AA was induced in all rats by intracutaneous injection of 0.1 mL Freund's complete adjuvant in the right paw on the 19th day. NC and MC groups were given (0.9%) physiological saline. The TPT and XFC groups were given TPT (10 mg/kg) and XFC (1.2 g/kg), respectively. Thirty days after administration, changes in paw edema (E), the arthritis index (AI), pulmonary function, levels of regulatory T-cells (Treg), ultrastructure of lung tissue, and expression of Notch receptors and ligands in lung tissue were observed. Results In the MC group, E and the AI were increased and pulmonary function significantly decreased; the structure of alveolar type-II cells was damaged; ratios of Treg in peripheral blood were reduced; and expression of Notch receptors such as Notch3 and Notch4 and ligands such as Delta1 in lung tissue were significantly increased whereas expression of Notch1, Jagged1 and Jagged2 were significantly decreased. After intervention with XFC, E and the AI were decreased; pulmonary function was enhanced; the structure of alveolar type-II cells was improved; and expression of Treg, Notch1, Jagged1, Jagged2 was elevated, whereas that of Notch3, Notch4 and Delta1 was reduced. Conclusion XFC can not only inhibit E and the AI and improve joint symptoms, it can also improve pulmonary function and reduce inflammation in lung tissue. These actions could be carried out through increases in the expression of Treg, Notch receptors (Notch1) and ligands (Jagged1, Jagged2), and reductions in the expression of Notch3, Notch4 and Delta1. These phenomena would reduce the deposition of immune complexes and the inflammatory response in lung tissue, thereby improving joint symptoms and pulmonary function.

Background This study aims to investigate the expression and significance of the αvβ6 integrin, collagen fibres and matrix metalloproteinases (MMP)-3 in oral squamous cell carcinoma (OSCC) and to analyse the possible regulatory relationships between αvβ6, collagen fibres and MMP-3. Materials and Methods A series of 80 patients (mean age 56.4 years) diagnosed with OSCC were enrolled. Associations between αvβ6, MMP-3, collagen fibre expression levels and clinicopathological parameters were evaluated using the Fisher exact test. Survival analysis was performed with Kaplan–Meier curves. Spearman rank correlation was used to analyse interactions between αvβ6, MMP-3 and collagen fibres. Results αvβ6 and MMP-3 were strongly expressed in human OSCC, especially at the peripheral borders of invasive tumour islands, and collagen fibres were generally disrupted and degraded in the same areas. The expression intensity of αvβ6 was associated with the differentiation state of cells. β6 mRNA was expressed in almost all cancer cells. In carcinomas, αvβ6 and MMP-3 expression were correlated with the distribution of collagen fibres. Conclusions Tumour cells highly expressing αvβ6 have a strong capability for invasion and migration, due to concomitant protease production and the destruction and remodelling of collagen fibres. Increased αvβ6 integrin and MMP-3 expression and collagen fibre changes in human OSCCs are related to unfavourable clinical prognostic factors and decreased survival.

Studies of sonodynamic therapy (SDT) have mainly focused on its direct cytotoxic effect on tumor cells. Its effects on the tumor microenvironment, especially angiogenesis, remain unknown. In this study, we found that SDT significantly inhibited endothelial cell proliferation, migration, invasion, and tube formation. Furthermore, in a tumor xenograft mouse model, SDT was found to remarkably suppress tumor growth, intratumoral vascularity, and expression of vascular endothelial growth factor in tumor cells. An ultrastructural study showed damage and disruption of tumor microvasculature after STD. Our results indicate that SDT inhibits neovascularization in tumor, which is partially responsible for the anti-tumor effect of SDT.

Background Type IV collagen (ColIV) is the most important scaffold for the basement membrane (BM) proteins, and plays an important role in regulating and limiting tumour invasion and metastasis. Methods Here, we observed the changes in morphology and distribution of type IV collagen (ColIV) in the basement membrane (BM) surrounding nests of carcinoma in 48 patients with oral tongue squamous cell (OTSCC). We examined the correlation between the expressions of ColIV, MMP-2 and MMP-9 and the prognosis of OTSCC patients. The intensity and patterns of expression were assessed immunohistochemically using anti-human mouse monoclonal MMP-2, MMP-9 and Col IV antibodies. Statistical analyses were performed to determine the prognostic correlations of ColIV, MMP-2, and MMP-9 levels. Results MMP-2 and MMP-9 expressions in OTSCC were higher than those in normal oral mucosa and dysplastic oral mucosa group(MMP-2 iOD: 66.40 ± 24.20, 134.69 ± 37.08, and 357.79 ± 116.78; MMP-9 iOD: 88.05 ± 23.85, 307.13 ± 93.22, and 791.31 ± 260.52; in normal, dysplastic oral mucosa, and tumour tissues, respectively, P < 0.01); however, ColIV immunoreactivity was lower (ColIV iOD: 406.87 ± 62.95, 247.83 ± 42.30, and 151.92 ± 38.17 in normal, dysplastic oral mucosa, and tumour tissues, respectively, P < 0.01). High tumour and stromal MMP-2 and MMP-9 expression was significantly associated with positive lymph node status. Col IV expression was associated with positive lymph node status (P < 0.05), and have negatively correlated with the expression of MMP-2 and MMP-9. Overall survival was significantly shorter in patients with high tumour and stromal MMP-2 and MMP-9 expression, and tended to be shorter in patients with low ColIV expression. Conclusions Degradation of ColIV was closely related to increased MMP-2 and MMP-9 expression; MMP-9 have more important function than MMP-2 during the cancer development. Monitoring changes in the expression of ColIV, MMP-2, and MMP-9 may be a useful technique for assessing prognoses in OTSCC patients.

Dumbbell-like Pt-Fe₃O₄ nanoparticles (NPs) were synthesized and used as a novel kind of label for the preparation of electrochemical immunosensor, which is applied to the detection of cancer biomarker squamous cell carcinoma antigen (SCC-Ag). The signal amplification strategy, using the synergetic effect present in Pt-Fe₃O₄ to increase the reduction ability of the NPs toward H₂O₂, improved the sensitivity of the immunosensor. Nitrogen-doped graphene sheets (N-GS) were synthesized from graphite oxides through thermal annealing of graphite oxides in ammonia, which was used to immobilize primary anti-SCC antibody (Ab₁). Secondary anti-SCC antibody (Ab₂) was adsorbed onto the Pt-Fe₃O₄ NPs. The immunosensor was prepared through a sandwich structure and displayed a wide linear range (0.05-18 ng/mL), low detection limit (15.3 pg/mL), good reproducibility and stability. The method has been applied to the analysis of clinical serum samples with satisfactory results. These labels for immunosensors can provide many potential applications for the detection of different biomolecules.