Polyphenols-based intelligent oral barrier membranes for periodontal bone defect reconstruction.

Periodontitis-induced periodontal bone defects significantly impact patients' daily lives. The guided tissue regeneration and guided bone regeneration techniques, which are based on barrier membranes, have brought hope for the regeneration of periodontal bone defects. However, traditional barrier membranes lack antimicrobial properties and cannot effectively regulate the complex oxidative stress microenvironment in periodontal bone defect areas, leading to unsatisfactory outcomes in promoting periodontal bone regeneration. To address these issues, our study selected the collagen barrier membrane as the substrate material and synthesized a novel barrier membrane (PO/4-BPBA/Mino@COL, PBMC) with an intelligent antimicrobial coating through a simple layer-by-layer assembly method, incorporating reactive oxygen species (ROS)-scavenging components, commercial dual-functional linkers and antimicrobial building blocks. Experimental results indicated that PBMC exhibited good degradability, hydrophilicity and ROS-responsiveness, allowing for the slow and controlled release of antimicrobial drugs. The outstanding antibacterial, antioxidant and biocompatibility properties of PBMC contributed to resistance to periodontal pathogen infection and regulation of the oxidative balance, while enhancing the migration and osteogenic differentiation of human periodontal ligament stem cells. Finally, using a rat periodontal bone defect model, the therapeutic effect of PBMC in promoting periodontal bone regeneration under infection conditions was confirmed. In summary, the novel barrier membranes designed in this study have significant potential for clinical application and provide a reference for the design of future periodontal regenerative functional materials.

TERC promotes non-small cell lung cancer progression by facilitating the nuclear localization of TERT.

The core of telomerase consists of the protein subunit telomerase reverse transcriptase (TERT) and the telomerase RNA component (TERC). So far, the role of TERC in cancer development has remained elusive. Here, we found TERC expression elevated in non-small cell lung cancer (NSCLC) tissues, which was associated with disease progression and poor prognosis in patients. Using NSCLC cell lines and xenograft models, we showed that knockdown of TERC caused cell cycle arrest, and inhibition of cell proliferation and migration. Mechanistically, TERC was exported to the cytoplasm by nuclear RNA export factor 1 (NXF1), where it mediated the interaction of TERT with other telomerase subunits. Depletion of TERC hindered the assembly and subsequent nuclear localization of the telomerase complex, preventing TERT from functioning in telomere maintenance and transcription regulation. Our findings suggest that TERC is a potential biomarker for NSCLC diagnosis and prognosis and can be a target for NSCLC treatment.

FLI1 promotes IFN-γ-induced kynurenine production to impair anti-tumor immunity.

Nasopharyngeal carcinoma (NPC)-mediated immunosuppression within the tumor microenvironment (TME) frequently culminates in the failure of otherwise promising immunotherapies. In this study, we identify tumor-intrinsic FLI1 as a critical mediator in impairing T cell anti-tumor immunity. A mechanistic inquiry reveals that FLI1 orchestrates the expression of CBP and STAT1, facilitating chromatin accessibility and transcriptional activation of IDO1 in response to T cell-released IFN-γ. This regulatory cascade ultimately leads to augmented IDO1 expression, resulting in heightened synthesis of kynurenine (Kyn) in tumor cells. This, in turn, fosters CD8+ T cell exhaustion and regulatory T cell (Treg) differentiation. Intriguingly, we find that pharmacological inhibition of FLI1 effectively obstructs the CBP/STAT1-IDO1-Kyn axis, thereby invigorating both spontaneous and checkpoint therapy-induced immune responses, culminating in enhanced tumor eradication. In conclusion, our findings delineate FLI1-mediated Kyn metabolism as an immune evasion mechanism in NPC, furnishing valuable insights into potential therapeutic interventions.

Polysaccharides Produced by Plant Growth-Promoting Rhizobacteria Strain Burkholderia sp. BK01 Enhance Salt Stress Tolerance to Arabidopsis thaliana.

Salt stress is one of the most serious abiotic stresses leading to reduced agricultural productivity. Polysaccharides from seaweed have been used as biostimulants to promote crop growth and improve plant resistance to abiotic stress. In this study, PGPR strain Burkholderia sp. BK01 was isolated from the rhizosphere of wheat, and it was characterized for phosphorus (Pi) dissolution, indole-3-acetic acid (IAA) production, ammonia (NH3) and exopolysaccharides (EPS). In particular, strain BK01 can efficiently produce extracellular polysaccharide with a yield of 12.86 g/L, using sorbitol as carbon source. BK01 EPS was identified as an heteropolysaccharide with Mw 3.559 × 106 Da, composed of (D)-galactose (75.3%), (D)-glucose (5.5%), (L)-rhamnose (5.5%), (D)-galactouronic acid (4.9%) and (D)-glucuronic acid (8.8%). The present work aims to highlight the effect of the BK01 EPS on growth and biochemical changes in Arabidopsis thaliana under salt stress (100 mM). The purified BK01 EPS at a concentration of 100 mg/L efficiently promoted the growth of plants in pot assays, improved the chlorophyll content, enhanced the activities of SOD, POD and CAT, and decreased the content of MDA. This results suggested that the polysaccharides produced by PGPR strain Burkholderia sp. BK01 can be used as biostimulants to promote plant growth and improve plant resistance to salt stress.

Radiomics and dosiomics for predicting radiation-induced hypothyroidism and guiding intensity-modulated radiotherapy.

To guide individualized intensity-modulated radiotherapy (IMRT), we developed and prospectively validated a multiview radiomics risk model for predicting radiation-induced hypothyroidism in patients with nasopharyngeal carcinoma. And simulated radiotherapy plans with same dose-volume-histogram (DVH) but different dose distributions were redesigned to explore the clinical application of the multiview radiomics risk model. The radiomics and dosiomics were built based on selected radiomics and dosiomics features from planning computed tomography and dose distribution, respectively. The multiview radiomics risk model that integrated radiomics, dosiomics, DVH parameters, and clinical factors had better performance than traditional normal tissue complication probability models. And multiview radiomics risk model could identify differences of patient hypothyroidism-free survival that cannot be stratified by traditional models. Besides, two redesigned simulated plans further verified the clinical application and advantage of the multiview radiomics risk model. The multiview radiomics risk model was a promising method to predict radiation-induced hypothyroidism and guide individualized IMRT.

Immunochemotherapy alone or immunochemotherapy plus subsequent locoregional radiotherapy in de novo metastatic nasopharyngeal carcinoma.

BACKGROUND: To demonstrate whether the benefit of locoregional radiotherapy in de novo metastatic nasopharyngeal carcinoma remains in the immunotherapy era and which patients can benefit from radiotherapy. MATERIALS AND METHODS: A total of 273 histopathology-confirmed de novo metastatic nasopharyngeal carcinoma was enrolled between May 2017 and October 2021 if receiving immunochemotherapy with or without subsequent intensity-modulated radiotherapy to the nasopharynx and neck. We compared the progression-free survival, overall survival, and safety between the two groups. Additionally, subgroup analysis was conducted and a scoring model was developed to identify suitable patients for radiation. RESULTS: There were 95 (34.8 %) patients with immunochemotherapy alone, and 178 (65.2 %) with immunochemotherapy plus subsequent locoregional radiotherapy. With a median follow-up time of 18 months, patients with immunochemotherapy plus subsequent radiotherapy had higher 1-year progression-free survival (80.6 % vs. 65.1 %, P < 0.001) and overall survival (98.3 % vs. 89.5 %, P = 0.001) than those with immunochemotherapy alone. The benefit was retained in multivariate analysis and propensity score-matched analysis. Mainly, it was more significant in patients with oligometastases, EBV DNA below 20,200 copies/mL, and complete or partial relapse after immunochemotherapy. The combined treatment added grade 3 or 4 anemia and radiotherapy-related toxicities. CONCLUSION: Immunochemotherapy plus subsequent locoregional radiotherapy prolonged the survival of de novo metastatic nasopharyngeal carcinoma with tolerable toxicities. A scoring model based on oligometastases, EBV DNA level, and response after immunochemotherapy could facilitate individualized management.

FLI1 regulates radiotherapy resistance in nasopharyngeal carcinoma through TIE1-mediated PI3K/AKT signaling pathway.

BACKGROUND: Radiotherapy resistance is the main cause of treatment failure in nasopharyngeal carcinoma (NPC), which leads to poor prognosis. It is urgent to elucidate the molecular mechanisms underlying radiotherapy resistance. METHODS: RNA-seq analysis was applied to five paired progressive disease (PD) and complete response (CR) NPC tissues. Loss-and gain-of-function assays were used for oncogenic function of FLI1 both in vitro and in vivo. RNA-seq analysis, ChIP assays and dual luciferase reporter assays were performed to explore the interaction between FLI1 and TIE1. Gene expression with clinical information from tissue microarray of NPC were analyzed for associations between FLI1/TIE1 expression and NPC prognosis. RESULTS: FLI1 is a potential radiosensitivity regulator which was dramatically overexpressed in the patients with PD to radiotherapy compared to those with CR. FLI1 induced radiotherapy resistance and enhanced the ability of DNA damage repair in vitro, and promoted radiotherapy resistance in vivo. Mechanistic investigations showed that FLI1 upregulated the transcription of TIE1 by binding to its promoter, thus activated the PI3K/AKT signaling pathway. A decrease in TIE1 expression restored radiosensitivity of NPC cells. Furthermore, NPC patients with high levels of FLI1 and TIE1 were correlated with poor prognosis. CONCLUSION: Our study has revealed that FLI1 regulates radiotherapy resistance of NPC through TIE1-mediated PI3K/AKT signaling pathway, suggesting that targeting the FLI1/TIE1 signaling pathway could be a potential therapeutic strategy to enhance the efficacy of radiotherapy in NPC.

The prognostic value and immune correlation of IL18 expression and promoter methylation in renal cell carcinoma.

BACKGROUND: Renal cell carcinoma (RCC) is not sensitive to immunotherapy and has poor prognosis. DNA methylation regulates gene expression, and its abnormal changes are related to many human diseases. Recently, DNA methylation has been found to participate in immune infiltration in various cancers. However, its pattern in RCC remains poorly understood. RESULTS: We found that IL18 was significantly over-expressed in RCC tumor tissues compared to normal adjacent tissues The IL18 promoter region was hypomethylated, which was strongly correlated with elevated IL18 mRNA expression, and predicted advanced clinicopathological characteristics and shorter overall survival. Furthermore, we found that IL18 promoter methylation was significantly related to the down-regulation of immune checkpoint molecules and increase of CD8 + T cell infiltration in RCC tumor tissues. CONCLUSIONS: We have identified the important role of IL18 promoter methylation and expression, which are associated with clinicopathological characteristics, overall survival, immune cell infiltration and expression of immune checkpoint molecules in RCC. We present the rationale for IL18 promoter methylation as a molecular biomarker for predicting the response of RCC to immune checkpoint inhibitors.

ROS-scavenging biomaterials for periodontitis.

Periodontitis is defined as a chronic inflammatory disease in which the continuous activation of oxidative stress surpasses the reactive oxygen species (ROS) scavenging capacity of the endogenous antioxidative defense system. Studies have demonstrated that ROS-scavenging biomaterials should be promising candidates for periodontitis therapy. To benefit the understanding and design of scavenging biomaterials for periodontitis, this review details the relationship between ROS and periodontitis, including direct and indirect damage, the application of ROS-scavenging biomaterials in periodontitis, including organic and inorganic ROS-scavenging biomaterials, and the various dosage forms of fabricated materials currently used for periodontal therapy. Finally, the current situation and further prospects of ROS-scavenging biomaterials in periodontal applications are summarized. Expecting that improved ROS-scavenging biomaterials could be better designed and developed for periodontal and even clinical application.

Role of postoperative chemoradiotherapy in head and neck cancer without positive margins or extracapsular extension: a propensity score-matching analysis.

BACKGROUND: The aim of this work was to determine whether patients with intermediate-risk head and neck squamous cell carcinoma (HNSCC) can benefit from postoperative chemoradiotherapy (POCRT). METHODS: Patients without extracapsular extension (ECE) or positive margins (PMs) who received POCRT or postoperative radiotherapy (PORT) at our center were retrospectively (December 2009 to October 2018) included for analysis, in particular, using a propensity score-matching method. RESULTS: After matching, 264 patients were enrolled, including 142 (41.2%) patients with pT3-4, 136 (38.3%) patients with pN2-3, 68 (21.1%) patients with perineural invasion, and 45 (12.8%) patients with lymphatic/vascular space invasion. With a median follow-up of 52 months, 3-year overall survival (OS), locoregional relapse-free survival (LRFS), distant metastasis-free survival (DMFS) and disease-free survival (DFS) rates were 72.4%, 79.3%, 83.5% and 62.5%, respectively. pN2-3 was an independent risk factor for OS (p < 0.001), DFS (p < 0.001), LRFS (p < 0.001) and DMFS (p = 0.002), while pT3-4 was a poor prognostic factor for DMFS (p = 0.005). Overall, patients receiving POCRT had no significant differences from those receiving PORT in OS (p = 0.062), DFS (p = 0.288), LRFS (p = 0.076) or DMFS (p = 0.692). But notably, patients with pN2-3 achieved better outcomes from POCRT than PORT in 3-year OS (p = 0.050, 63.9% vs. 47.9%) and LRFS (p = 0.019, 74.6% vs. 54.9%). And patients with pT3-4 also had higher 3-year LRFS (p = 0.014, 88.5% vs. 69.1%) if receiving POCRT. CONCLUSIONS: Among all intermediate-risk pathological features, pN2-3 and pT3-4 were independent unfavorable prognostic factors for patients with HNSCC without PMs or ECE. POCRT can improve the survival outcomes of patients with pN2-3 or pT3-4.

A universal coating strategy for inhibiting the growth of bacteria on materials surfaces.

The development of a versatile antibacterial coating, irrespective of material characteristics, is greatly attractive but still a challenge. In this work, mussel-inspired dopamine-modified sodium alginate (SA-DA) was successfully synthesized as the adhesion layer, and antibacterial coatings on three types of substrates, namely cotton fabric, aluminum sheet, and polyurethane membrane, were constructed through the layer-by-layer (LbL) deposition of polyhexamethylene guanidine and sodium alginate. Among the coated materials, the coated cotton fabric was systematically characterized, and the results showed that it still exhibited ideal hydrophilicity, and its liquid absorption capacity increased with an increase in the coating layers. The growth of Escherichia coli and Staphylococcus aureus was notably inhibited on the coated cotton fabric, and 10 coating bilayers achieved 100% inhibition of bacterial growth within 10 min. Furthermore, an ideal antibacterial ability maintained after 10 cycles of antibacterial trials or 50 washing or soaping cycles. In vitro evaluation of the hemostatic effect indicated that the coated cotton fabric could promote blood clotting by concentrating the components of blood and activating the platelets, and no significant hemolysis and cytotoxicity were observed in the coated cotton fabric. Moreover, the coated aluminum and polyurethane film also displayed an obvious antibacterial effect, which proved that the constructed coating could successfully adhere to the metal and polymer surfaces. Therefore, this work provided a proper way for the progress of a current antibacterial coating tactics for different substrate surfaces.

Development and validation of radiologic scores for guiding individualized induction chemotherapy in T3N1M0 nasopharyngeal carcinoma.

OBJECTIVES: We aimed to develop and validate radiologic scores from [18F]FDG PET/CT and MRI to guide individualized induction chemotherapy (IC) for patients with T3N1M0 nasopharyngeal carcinoma (NPC). METHODS: A total of 542 T3N1M0 patients who underwent pretreatment [18F]FDG PET/CT and MRI were enrolled in the training cohort. A total of 174 patients underwent biopsy of one or more cervical lymph nodes. Failure-free survival (FFS) was the primary endpoint. The radiologic score, which was calculated according to the number of risk factors from the multivariate model, was used for risk stratification. The survival difference of patients undergoing concurrent chemoradiotherapy (CCRT) with or without IC was then compared in risk-stratified subgroups. Another cohort from our prospective clinical trial (N = 353, NCT03003182) was applied for validation. RESULTS: The sensitivity of [18F]FDG PET/CT was better than that of MRI (97.7% vs. 87.1%, p < 0.001) for diagnosing histologically proven metastatic cervical lymph nodes. Radiologic lymph node characteristics were independent risk factors for FFS (all p < 0.05). High-risk patients (n = 329) stratified by radiologic score benefited from IC (5-year FFS: IC + CCRT 83.5% vs. CCRT 70.5%; p = 0.0044), while low-risk patients (n = 213) did not. These results were verified again in the validation cohort. CONCLUSIONS: T3N1M0 patients were accurately staged by both [18F]FDG PET/CT and MRI. The radiologic score can correctly identify high-risk patients who can gain additional survival benefit from IC and it can be used to guide individualized treatment of T3N1M0 NPC. KEY POINTS: • [18F]FDG PET/CT was more accurate than MRI in diagnosing histologically proven cervical lymph nodes. • Radiologic lymph node characteristics were reliable independent risk factors for FFS in T3N1M0 nasopharyngeal carcinoma patients. • High-risk patients identified by the radiologic score based on [18F]FDG PET/CT and MRI could benefit from the addition of induction chemotherapy.

The Bio-Aging of Biofilms on Behalf of Various Oral Status on Different Titanium Implant Materials.

The properties of titanium implants are affected by bio-aging due to long-term exposure to the oral microenvironment. This study aimed to investigate probable changes in titanium plates after different biofilm bio-aging processes, representing various oral status. Titanium plates with different surface treatments were used, including polish, sandblasted with large grit and acid etched (SLA), microarc oxidation (MAO), and hydroxyapatite coating (HA). We established dual-species biofilms of Staphylococcus aureus (S. aureus)-Candida albicans (C. albicans) and saliva biofilms from the healthy and patients with stage III-IV periodontitis, respectively. After bio-aging with these biofilms for 30 days, the surface morphology, chemical composition, and water contact angles were measured. The adhesion of human gingival epithelial cells, human gingival fibroblasts, and three-species biofilms (Streptococcus sanguis, Porphyromonas gingivalis, and Fusobacterium nucleatum) were evaluated. The polished specimens showed no significant changes after bio-aging with these biofilms. The MAO- and SLA-treated samples showed mild corrosion after bio-aging with the salivary biofilms. The HA-coated specimens were the most vulnerable. Salivary biofilms, especially saliva from patients with periodontitis, exhibited a more distinct erosion on the HA-coating than the S. aureus-C. albicans dual-biofilms. The coating became thinner and even fell from the substrate. The surface became more hydrophilic and more prone to the adhesion of bacteria. The S. aureus-C. albicans dual-biofilms had a comparatively mild corrosion effect on these samples. The HA-coated samples showed more severe erosion after bio-aging with the salivary biofilms from patients with periodontitis compared to those of the healthy, which emphasized the importance of oral hygiene and periodontal health to implants in the long run.

Development and prospective validation of a risk score model in guiding individualized concurrent chemoradiotherapy in stage II nasopharyngeal carcinoma in intensity-modulated radiotherapy era.

PURPOSE: We aimed to develop and prospectively validate a risk score model to guide individualized concurrent chemoradiotherapy (CCRT) for patients with stage II nasopharyngeal carcinoma (NPC) in intensity-modulated radiotherapy (IMRT) era. MATERIALS AND METHODS: In total, 1220 patients who received CCRT or IMRT alone were enrolled in this study, including a training cohort (n = 719), a validation cohort (n = 307), and a prospective test cohort (n = 194). Patients were stratified into different risk groups by a risk score model based on independent prognostic factors, which were developed in the training cohort. Survival rates were compared by the log-rank test. The validation and prospective test cohorts were used for validation. RESULTS: Total tumor volume, Epstein-Barr virus DNA, and lactate dehydrogenase were independent risk factors for failure-free survival (FFS, all p < 0.05). A risk score model based on these three risk factors was developed to classify patients into low-risk group (no risk factor, n = 337) and high-risk group (one or more factors, n = 382) in the training cohort. In the high-risk group, CCRT had better survival rates than IMRT alone (5-year FFS: 82.6% vs. 74.0%, p = 0.028). However, there was no survival difference between CCRT and IMRT alone either in the whole training cohort (p = 0.15) or in the low-risk group (p = 0.15). The results were verified in the validation and prospective test cohorts. CONCLUSION: A risk score model was developed and prospectively validated to precisely select high-risk stage II NPC patients who can benefit from CCRT, and thus guided individualized treatment in IMRT era.

Benefit of [18F]-FDG PET/CT for treatment-naïve nasopharyngeal carcinoma.

BACKGROUND: To test the advantages of positron emission tomography and computed tomography (PET/CT) for diagnosing lymph nodes and staging nasopharyngeal carcinoma and to investigate its benefits for survival and treatment decisions. METHODS: The performance of PET/CT and magnetic resonance imaging (MRI) in diagnosis was compared based on 460 biopsied lymph nodes. Using the propensity matching method, survival differences of T3N1M0 patients with (n = 1093) and without (n = 1377) PET/CT were compared in diverse manners. A radiologic score model was developed and tested in a subset of T3N1M0 patients. RESULTS: PET/CT performed better than MRI with higher sensitivity, accuracy, and area under the receiver operating characteristic curve (96.7% vs. 88.5%, p < 0.001; 88.0% vs. 81.1%, p < 0.001; 0.863 vs. 0.796, p < 0.05) in diagnosing lymph nodes. Accordingly, MRI-staged T3N0-3M0 patients showed nondifferent survival rates, as they were the same T3N1M0 if staged by PET/CT. In addition, patients staged by PET/CT and MRI showed higher survival rates than those staged by MRI alone (p < 0.05), regardless of the Epstein-Barr virus DNA load. Interestingly, SUVmax-N, nodal necrosis, and extranodal extension were highly predictive of survival. The radiologic score model based on these factors performed well in risk stratification with a C-index of 0.72. Finally, induction chemotherapy showed an added benefit (p = 0.006) for the high-risk patients selected by the model but not for those without risk stratification (p = 0.78). CONCLUSION: PET/CT showed advantages in staging nasopharyngeal carcinoma due to a more accurate diagnosis of lymph nodes and this contributed to a survival benefit. PET/CT combined with MRI provided prognostic factors that could identify high-risk patients and guide individualized treatment.

Prognostic values of treatment modalities on head and neck mucosal melanomas in elderly patients: a population-based analysis.

BACKGROUND: Head and neck mucosal melanoma (HNMM) is defined as a rare malignant tumor derived from melanocytes. There is no consensus regarding the treatment protocol for HNMM in elderly patients. METHODS: The National Cancer Institute's Surveillance, Epidemiology, and End Results database was used to identify elderly patients diagnosed with HNMM from 1975 to 2016. The chi-squared test was used to compare patient characteristics. The reverse Kaplan-Meier method was used to estimate the median follow-up time. The Kaplan-Meier method and log-rank test were used to estimate and compare the overall survival (OS) and disease-specific survival (DSS) of the groups. Cox regression analysis was used to evaluate the risk factors for OS and DSS of HNMM. RESULTS: Our retrospective study included 828 elderly patients with HNMM, and the 5-year OS and DSS rates were 22.4% and 27.4%, respectively. After adjusting for other variables in multivariate analysis, patients undergoing radiotherapy alone had worse OS [hazard ratio (HR) =1.449, 95% confidence interval (CI): 1.010-1.742, P=0.006] and DSS (HR =1.656, 95% CI: 1.257-2.181, P<0.001) than those undergoing surgery alone. No significant difference in OS (HR =0.892, 95% CI: 0.753-1.056, P=0.183) or DSS (HR =0.917, 95% CI: 0.764-1.101, P=0.354) was observed for patients undergoing surgery with or without radiotherapy. Our analysis of the subgroup of patients with complete clinical staging information demonstrated that the effects of surgery alone on OS (HR =0.734, 95% CI: 0.562-0.958, P=0.023) were inferior to those of surgery with radiotherapy, but no significant difference was noted compared with radiotherapy alone. CONCLUSIONS: The survival of elderly patients with HNMM is increased with the combination of surgery and radiotherapy compared with surgery alone and radiotherapy alone. In addition, the population-based analysis demonstrated that combination therapy exhibited an obviously increased usage rate from 1975 to 2016, representing a mainstream treatment modality.

LINC00460 promotes pancreatic cancer progression by sponging miR-491-5p.

BACKGROUND: A growing body of studies have suggested that LINC00460 is instrumental in tumorigenesis and tumour progression. Nonetheless, the biological function and mechanisms of LINC00460 in pancreatic ductal adenocarcinoma (PDAC) remain vague. METHODS: Analysis based on public databases and a quantitative reverse transcription-polymerase chain reaction were performed to screen for differentially expressed lncRNAs in PDAC and to detect LINC00460 expression in PDAC cell lines and clinical samples. The survival of patients in the up-regulated and down-regulated LINC00460 expression groups was compared by using the Kaplan-Meier method. In addition, the potential biological functions of LINC00460 in PDAC were explored by cell counting kit-8, colony formation, flow cytometry and transwell assays. Furthermore, bioinformatics analysis, luciferase reporter assays and rescue experiments were applied to demonstrate the mechanism by which LINC00460 could directly bind to and inhibit miR-491-5p. RESULTS: LINC00460 is up-regulated in PDAC and correlates with adverse survival outcomes. The results of functional tests verified that LINC00460 knockdown inhibited both cell proliferation and cell migration. Additionally, knockdown led to G0/G1 cell cycle blockage and enhanced cell apoptosis. Mechanistic investigations revealed that LINC00460 directly binds to and attenuates the tumour suppressor miR-491-5p, thus accelerating PDAC progression. CONCLUSIONS: This research showed that LINC00460 is overexpressed in PDAC and correlates with adverse clinical outcomes. Additionally, LINC00460 promotes the aggressiveness of PDAC by targeting miR-491-5p. Thus, LINC00460 may serve as diagnostic biomarker of PDAC and a new target for PDAC therapy.

Effect of Induction Chemotherapy in Nasopharyngeal Carcinoma: An Updated Meta-Analysis.

BACKGROUND: Previous meta-analysis had evaluated the effect of induction chemotherapy in nasopharyngeal carcinoma. But two trials with opposite findings were not included and the long-term result of another trial significantly differed from the preliminary report. This updated meta-analysis was thus warranted. METHODS: Literature search was conducted to identify randomized controlled trials focusing on the additional efficacy of induction chemotherapy in nasopharyngeal carcinoma. Trial-level pooled analysis of hazard ratio (HR) for progression free survival and overall survival and risk ratio (RR) for locoregional control rate and distant control rate were performed. RESULTS: Twelve trials were eligible. The addition of induction chemotherapy significantly prolonged both progression free survival (HR=0.68, 95% confidence interval [CI] 0.60-0.76, p<0.001) and overall survival (HR=0.67, 95% CI 0.54-0.80, p<0.001), with 5-year absolute benefit of 11.31% and 8.95%, respectively. Locoregional (RR=0.80, 95% CI 0.70-0.92, p=0.002) and distant control (RR=0.70, 95% CI 0.62-0.80) rates were significantly improved as well. The incidence of grade 3-4 adverse events during the concurrent chemoradiotherapy was higher in leukopenia (p=0.028), thrombocytopenia (p<0.001), and fatigue (p=0.038) in the induction chemotherapy group. CONCLUSIONS: This meta-analysis supported that induction chemotherapy could benefit patients with nasopharyngeal carcinoma in progression free survival, overall survival, locoregional, and distant control rate.

Atg7-Mediated Autophagy Is Involved in the Neural Crest Cell Generation in Chick Embryo.

Autophagy plays a very important role in numerous physiological and pathological events. However, it still remains unclear whether Atg7-induced autophagy is involved in the regulation of neural crest cell production. In this study, we found the co-location of Atg7 and Pax7+ neural crest cells in early chick embryo development. Upregulation of Atg7 with unilateral transfection of full-length Atg7 increased Pax7+ and HNK-1+ cephalic and trunk neural crest cell numbers compared to either Control-GFP transfection or opposite neural tubes, suggesting that Atg7 over-expression in neural tubes could enhance the production of neural crest cells. BMP4 in situ hybridization and p-Smad1/5/8 immunofluorescent staining demonstrated that upregulation of Atg7 in neural tubes suppressed the BMP4/Smad signaling, which is considered to promote the delamination of neural crest cells. Interestingly, upregulation of Atg7 in neural tubes could significantly accelerate cell progression into the S phase, implying that Atg7 modulates cell cycle progression. However, ß-catenin expression was not significantly altered. Finally, we demonstrated that upregulation of the Atg7 gene could activate autophagy as did Atg8. We have also observed that similar phenotypes, such as more HNK-1+ neural crest cells in the unilateral Atg8 transfection side of neural tubes, and the transfection with full-length Atg8-GFP certainly promote the numbers of BrdU+ neural crest cells in comparison to the GFP control. Taken together, we reveal that Atg7-induced autophagy is involved in regulating the production of neural crest cells in early chick embryos through the modification of the cell cycle.

Excess Imidacloprid Exposure Causes the Heart Tube Malformation of Chick Embryos.

As a neonicotinoid pesticide, imidacloprid is widely used to control sucking insects on agricultural planting and fleas on domestic animals. However, the extent to which imidacloprid exposure has an influence on cardiogensis in early embryogenesis is still poorly understood. In vertebrates, the heart is the first organ to be formed. In this study, to address whether imidacloprid exposure affects early heart development, the early chick embryo has been used as an experimental model because of its accessibility at its early developmental stage. The results demonstrate that exposure of the early chick embryo to imidacloprid caused malformation of heart tube. Furthermore, the data reveal that down-regulation of GATA4, NKX2.5, and BMP4 and up-regulation of Wnt3a led to aberrant cardiomyocyte differentiation. In addition, imidacloprid exposure interfered with basement membrane breakdown, E-cadherin/laminin expression, and mesoderm formation during the epithelial-mesenchymal transition (EMT) in gastrula chick embryos. Finally, the DiI-labeled cell migration trajectory indicated that imidacloprid restricted the cell migration of cardiac progenitors to primary heart field in gastrula chick embryos. A similar observation was also obtained from the cell migration assay of scratch wounds in vitro. Additionally, imidacloprid exposure negatively affected the cytoskeleton structure and expression of corresponding adhesion molecules. Taken together, these results reveal that the improper EMT, cardiac progenitor migration, and differentiation are responsible for imidacloprid exposure-induced malformation of heart tube during chick embryo development.