Isoliquiritigenin diminishes invasiveness of human nasopharyngeal carcinoma cells associating with inhibition of MMP-2 expression and STAT3 signalling.

Nasopharyngeal carcinoma (NPC) is prevalent in Asia and exhibits highly metastatic characteristics, leading to uncontrolled disease progression. Isoliquiritigenin (ISL) have attracted attention due to their diverse biological and pharmacological properties, including anticancer activities. However, the impact of ISL on the invasive and migratory ability of NPC remains poorly understood. Hence, this study aimed to investigate the in vitro anti-metastatic effects of ISL on NPC cells and elucidate the underlying signalling pathways. Human NPC cell NPC-39 and NPC-BM were utilized as cell models. Migratory and invasive capabilities were evaluated through wound healing and invasion assays, respectively. Gelatin zymography was employed to demonstrate matrix metalloproteinase-2 (MMP-2) activity, while western blotting was conducted to analyse protein expression levels and explore signalling cascades. Overexpression of signal transducer and activator of transcription 3 (STAT3) was carried out by transduction of STAT3-expressing vector. Our findings revealed that ISL effectively suppressed the migration and invasion of NPC cells. Gelatin zymography and Western blotting assays demonstrated that ISL treatment led to a reduction in MMP-2 enzyme activity and protein expression. Investigation of signalling cascades revealed that ISL treatment resulted in the inhibition of STAT3 phosphorylation. Moreover, overexpression of STAT3 restored the migratory ability of NPC cells in the presence of ISL. Collectively, these findings indicate that ISL inhibits the migration and invasion of NPC cells associating with MMP-2 downregulation through suppressing STAT3 activation. This suggests that ISL has an anti-metastatic effect on NPC cells and has potential therapeutic benefit for NPC treatment.

Simultaneous detection of miRNA and mRNA at the single-cell level in plant tissues.

Detecting the simultaneous presence of a microRNA (miRNA) and a mRNA in a specific tissue can provide support for the prediction that the miRNA regulates the mRNA. Although two such methods have been developed for mammalian tissues, they have a low signal-noise ratio and/or poor resolution at the single-cell level. To overcome these drawbacks, we develop a method that uses sequence-specific miRNA-locked nucleic acid (LNA) and mRNA-LNA probes. Moreover, it augments the detection signal by rolling circle amplification, achieving a high signal-noise ratio at the single-cell level. Dot signals are counted for determining the expression levels of mRNA and miRNA molecules in specific cells. We show a high sequence specificity of our miRNA-LNA probe, revealing that it can discriminate single-base mismatches. Numerical quantification by our method is tested in transgenic rice lines with different gene expression levels. We conduct several applications. First, the spatial expression profiling of osa-miR156 and OsSPL12 in rice leaves reveals their specific expression in mesophyll cells. Second, studying rice and its mutant lines with our method reveals opposite expression patterns of miRNA and its target mRNA in tissues. Third, the dynamic expression profiles of ZmGRF8 and zma-miR396 during maize leaf development provide evidence that zma-miR396 regulates the preferential spatial expression of ZmGRF8 in bundle sheath cells. Finally, our method can be scaled up to simultaneously detect multiple miRNAs and mRNAs in a tissue. Thus, it is a sensitive and versatile technique for studying miRNA regulation of plant tissue development.

Correlation between coronary heart disease severity and subsequent chronic rhinosinusitis severity: A retrospective cohort study.

Coronary heart disease (CHD) is associated with the development of several diseases. This retrospective population-based cohort study investigated the association between CHD severity and subsequent chronic rhinosinusitis (CRS) of varying severity. We used data from Taiwan's National Health Insurance Research Database. CHD was categorized as severe if treated using a coronary artery bypass graft (CABG) and as mild if treated with percutaneous coronary intervention (PCI). The primary outcome of this study was the development of CRS or severe CRS treated using functional endoscopic sinus surgery. Cox proportional hazards regression was used to calculate adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for CRS and severe CRS in different patient groups. We included 31,784 patients who received PCI surgery (the CHD-PCI group) and 15,892 patients who received CABG surgery (the CHD-CABG group). A total of 813 and 482 episodes of CRS occurred in the CHD-PCI and CHD-CABG groups, respectively, and 45 and 16 severe CRS events occurred in the CHD-PCI and CHD-CABG groups, respectively. Our multivariable analysis demonstrated that the incidence of CRS in the CHD-CABG group was significantly higher than that in the CHD-PCI group (aHR: 1.196, 95% CI: 1.064-1.280, P = 0.0402), but the two groups had similar incidence rates of severe CRS (aHR: 0.795, 95% CI: 0.456-1.388, P = 0.5534). Subgroup analyses revealed that the association between CHD severity and CRS development was more significant among men (P = 0.0016). In conclusion, we determined that severe CHD treated with CABG was associated with a higher incidence of subsequent CRS, and this association was more prominent among men.

Dihydromyricetin inhibits cancer cell migration and matrix metalloproteinases-2 expression in human nasopharyngeal carcinoma through extracellular signal-regulated kinase signaling pathway.

Nasopharyngeal carcinoma (NPC) is endemic in Southeast Asia and the main cause of treatment failure is metastasis. A lot of biological and pharmacological actions of dihydromyricetin (DHM) have been reported such as regulating glucose and anti-cancer effects. The effects of DHM on the cancer invasion and migration of NPC, however, are still unclear. We therefore investigated the in vitro anti-metastatic properties of DHM on three human NPC cell lines (HONE-1, NPC-39, and NPC-BM), as well as the underlying signaling pathways. Our study revealed that DHM could suppress the migration and invasion in NPC cells. Gelatin zymography assay and western blotting assays demonstrated that DHM suppressed the enzyme activity and protein expression of matrix metalloproteinases-2 (MMP-2). Mitogen-activated protein kinases were also investigated to elucidate the signaling pathway, which showed that phosphorylation of extracellular signal-regulated kinase 1 and 2 (ERK1/2) was inhibited after the treatment of DHM. In conclusion, our data revealed that DHM inhibited the migration and invasion of NPC cells by suppressing the expression of MMP-2 via down regulating the ERK1/2 signaling pathway.

Comparison of the target-controlled infusion and the manual infusion of propofol anesthesia during electroconvulsive therapy: an open-label randomized controlled trial.

BACKGROUND: Target-controlled infusion (TCI) of propofol is a well-established method of procedural sedation and has been used in Japan for anesthesia during electroconvulsive therapy (ECT). However, the usefulness of the TCI of propofol for ECT has yet to be determined. This study aimed to compare the TCI and manual infusion (MI) of propofol anesthesia during ECT. METHODS: A total of forty psychiatric inpatients receiving bitemporal ECT were enrolled in the present study and randomized into the TCI group (N = 20) and the MI group (N = 20). Clinical Global Impression (CGI) and Montreal Cognitive Assessment (MoCA) scores were measured before and after ECT. The clinical outcomes, anesthesia-related variables, and ECT-related variables were compared between the two groups. Generalized estimating equations (GEEs) were used to model the comparison throughout the course of ECT. RESULTS: A total of 36 subjects completed the present study, with 18 subjects in each group. Both the groups didn't significantly differ in the post-ECT changes in CGI and MoCA scores. However, concerning MoCA scores after 6 treatments of ECT, the MI group had improvement while the TCI group had deterioration. Compared with the MI group, the TCI group had higher doses of propofol, and longer procedural and recovery time. The TCI group seemed to have more robust seizures in the early course of ECT but less robust seizures in the later course of ECT compared with the MI group. CONCLUSIONS: The present study does not support the use of TCI of propofol for anesthesia of ECT. TRIAL REGISTRATION: (ClinicalTrials.gov): NCT03863925 . Registered March 5, 2019 - Retrospectively registered.

Morusin Suppresses Cancer Cell Invasion and MMP-2 Expression through ERK Signaling in Human Nasopharyngeal Carcinoma.

The most important cause of treatment failure of nasopharyngeal carcinoma (NPC) patients is metastasis, including regional lymph nodes or distant metastasis, resulting in a poor prognosis and challenges for treatment. In the present study, we investigated the in vitro anti- tumoral properties of morusin on human nasopharyngeal carcinoma HONE-1, NPC-39, and NPC-BM cells. Our study revealed that morusin suppressed the migration and invasion abilities of the three NPC cells. Gelatin zymography assay and Western blotting demonstrated that the enzyme activity and the level of matrix metalloproteinases-2 (MMP-2) protein were downregulated by the treatment of morusin. Mitogen-activated protein kinase proteins were examined to identify the signaling pathway, which showed that phosphorylation of ERK1/2 was inhibited after the treatment of morusin. In summary, our data showed that morusin inhibited the migration and invasion of NPC cells by suppressing the expression of MMP-2 by downregulating the ERK1/2 signaling pathway, suggesting that morusin may be a potential candidate for chemoprevention or adjuvant therapy of NPC.

Epigallocatechin-3-gallate inhibits migration of human nasopharyngeal carcinoma cells by repressing MMP-2 expression.

Metastasis of the cancer cells to the regional lymph nodes parts of the body remains an important cause of treatment failure in nasopharyngeal carcinoma (NPC) patients. Epigallocatechin-3-gallate (EGCG), the most important ingredient in the green tea, has been reported to possess antioxidant and anticancer activities. However, the effects of EGCG on NPC cell metastasis are still unclear. In the present study, we examined the in vitro antimetastatic properties of EGCG on human NPC cells, NPC-39, HONE-1 and NPC-BM. The results revealed that EGCG considerably inhibited the migration abilities of three NPC cells. The matrix metalloproteinases-2 (MMP-2) activity and expression were also significantly inhibited by EGCG treatment. Furthermore, EGCG suppressed the phosphorylation of the Src signaling pathway. Moreover, blocking the Src pathway also inhibits MMP-2 expression and migration in the NPC cells. In conclusion, this study revealed that EGCG could inhibit the metastatic activity of human NPC cells by downregulating the protein expression of MMP-2 through modulation of the Src signaling pathway, suggesting that EGCG may be a potential candidate for chemoprevention of NPC.

Pterygomandibular suspension suture: a simple modification of uvulopalatopharyngoplasty for severe obstructive sleep apnea.

BACKGROUNDS: The aim of this study is to introduce pterygomandibular suspension suture as a simple modification of uvulopalatopharyngoplasty for severe obstructive sleep apnea in dealing with lateral pharyngeal wall and retropalatal space collapse. METHODS: This retrospective study was conducted at Taipei Veterans General Hospital, Taiwan. Ten adult patients underwent modified uvulopalatopharyngoplasty with pterygomandibular suspension suture according to following inclusion criteria: severe obstructive sleep apnea (apnea-hypopnea index [AHI] > 30 events/h), type I Fujita with lateral pharyngeal wall collapse, and failure for continuous positive airway pressure (CPAP) therapy. The philosophy of this modification technique is to create a firm anterolateral suspension of the lateral pharyngeal wall and soft palate by sutures. RESULTS: The mean operative time of modified uvulopalatopharyngoplasty with pterygomandibular suspension suture was 60 min. The mean AHI decreased significantly from 77.2 ± 25.0 preoperatively to 28.7 ± 18.8 postoperatively (P = 0.005) and the lowest oxygen saturation increased from 69.9 ± 11.4 to 81.1 ± 7.19% (P = 0.005). No major perioperative complication such as massive bleeding or respiratory distress was noted. No patient experienced a swallowing disturbance, taste change, or voice change 6 months postoperatively. The mean period for resuming a normal diet was 15 days. CONCLUSION: Modified uvulopalatopharyngoplasty with pterygomandibular suspension suture is a simplified and effective surgical approach with satisfactory functional recovery for selective patients with severe obstructive sleep apnea.

Phytoplasma SAP11 alters 3-isobutyl-2-methoxypyrazine biosynthesis in Nicotiana benthamiana by suppressing NbOMT1.

Phytoplasmas are bacterial phytopathogens that release virulence effectors into sieve cells and act systemically to affect the physiological and morphological state of host plants to promote successful pathogenesis. We show here that transgenic Nicotiana benthamiana lines expressing the secreted effector SAP11 from Candidatus Phytoplasma mali exhibit an altered aroma phenotype. This phenomenon is correlated with defects in the development of glandular trichomes and the biosynthesis of 3-isobutyl-2-methoxypyrazine (IBMP). IBMP is a volatile organic compound (VOC) synthesized by an O-methyltransferase, via a methylation step, from a non-volatile precursor, 3-isobutyl-2-hydroxypyrazine (IBHP). Based on comparative and functional genomics analyses, NbOMT1, which encodes an O-methyltransferase, was found to be highly suppressed in SAP11-transgenic plants. We further silenced NbOMT1 through virus-induced gene silencing and demonstrated that this enzyme influenced the accumulation of IBMP in N. benthamiana In vitro biochemical analyses also showed that NbOMT1 can catalyse IBHP O-methylation in the presence of S-adenosyl-L-methionine. Our study suggests that the phytoplasma effector SAP11 has the ability to modulate host VOC emissions. In addition, we also demonstrated that SAP11 destabilized TCP transcription factors and suppressed jasmonic acid responses in N. benthamiana These findings provide valuable insights into understanding how phytoplasma effectors influence plant volatiles.

Transgenic plants that express the phytoplasma effector SAP11 show altered phosphate starvation and defense responses.

Phytoplasmas have the smallest genome among bacteria and lack many essential genes required for biosynthetic and metabolic functions, making them unculturable, phloem-limited plant pathogens. In this study, we observed that transgenic Arabidopsis (Arabidopsis thaliana) expressing the secreted Aster Yellows phytoplasma strain Witches' Broom protein11 shows an altered root architecture, similarly to the disease symptoms of phytoplasma-infected plants, by forming hairy roots. This morphological change is paralleled by an accumulation of cellular phosphate (Pi) and an increase in the expression levels of Pi starvation-induced genes and microRNAs. In addition to the Pi starvation responses, we found that secreted Aster Yellows phytoplasma strain Witches' Broom protein11 suppresses salicylic acid-mediated defense responses and enhances the growth of a bacterial pathogen. These results contribute to an improved understanding of the role of phytoplasma effector SAP11 and provide new insights for understanding the molecular basis of plant-pathogen interactions.

L48H37, a curcumin analog, suppresses matrix metalloproteinase-9 expression and activity to hamper nasopharyngeal cancer cell migration.

OBJECTIVE: Metastatic disease is a major issue of treatment failure in nasopharyngeal carcinoma (NPC) patients and often linked to high mortality. L48H37, a synthetic analog of curcumin with augmented bioavailability over its parent compound, has demonstrated several oncostatic characteristics. This study was aimed to explore the anti-metastatic effect of L48H37 on NPC cancer cells and its underlying mechanism. METHODS: Cell viability was evaluated using MTT assay. Regulation of signaling pathways was elucidated by immunoblotting, and specific kinase inhibitors. RESULTS: In this study, we showed that L48H37 suppressed TPA-stimulated invasive and migratory capacities of NPC cell lines and gave rise to very little cytotoxic responses. Such anti-cancer effect of L48H37 was accompanied with attenuated expression levels and enzymatic activities of matrix metalloproteinase-9 (MMP-9), a pivotal mediator of metastatic processes. In addition, L48H37 interfered with TPA-induced JNK activation, and the treatment of L48H37 combined with a JNK antagonist demonstrated a synergistic effect on restraining TPA-stimulated MMP-9 activity and migration events in NPC cells. CONCLUSIONS: Our results revealed that L48H37 impeded the invasive potential of NPC cells via impairment of MMP-9 function and abundance, highlighting possible complementary therapies using curcumin or its effective analogs to manage NPC dissemination.

Post-irradiation dysbiosis in patients with nasopharyngeal carcinoma having received radiotherapy - A pilot study.

OBJECTIVE: To compare the changes in the sinonasal mucosa microbiome in patients with nasopharyngeal carcinoma (NPC) before and after radiotherapy (RT), and to explore the pathogenesis of post-irradiation chronic rhinosinusitis (PI-CRS) and its association with dysbiosis. STUDY DESIGN: Prospective cohort study. SETTING: Unicenter, Tertiary referral hospital. METHODS: Included patients newly diagnosed with NPC. Samples of ostiomeatal complex mucosa were collected before and after RT. Microbiome analysis was conducted using 16S rRNA sequencing, and statistical analysis was performed. Subgroup analyses based on RT modality (proton therapy or photon therapy) RESULTS: Total of 18 patients were enrolled in the study, with 62.1% receiving intensity-modulated proton therapy (IMPT). Corynebacterium was the most dominant genus identified in both the pre- and post-RT groups, with a visible increase in Staphylococcus and a decrease in Fusobacterium genus in post-RT group. Alpha-diversity did not significantly differ between groups, although the beta-diversity analysis revealed a dispersed microbiota in the post-RT group. The functional prediction indicated a higher relative abundance of taxonomies associated with biofilm formation in the post-RT group. The subgroup analysis revealed the above changes to be more significant in patients who received photon therapy (Intensity modulated radiation therapy, IMRT). CONCLUSIONS: This is the first study to analyze the microbiome of patients with NPC after IMPT. We identified similarities between the post-RT microenvironment and that reported in patients with CRS, with a more apparent change noted in patients treated with IMRT. Further investigation is required to further elucidate the pathogenesis of PI-CRS and its relationship to post-RT dysbiosis, particularly IMPT.

Impact of LINC00312 gene polymorphism coupled with habitual risks on buccal mucosa cancer.

Oral squamous cell carcinoma (OSCC) is a prevalent and lethal malignancy with a diverse etiology. LINC00312 is a long intergenic non-coding RNA that functions as a signal hub to regulate the progression and treatment of head and neck cancer. The aim of this study was to evaluate the effect of LINC00312 single nucleotide polymorphisms (SNPs) on the development of oral cancer. Two LINC00312 SNPs, namely rs12497104 and rs164966, were investigated among 469 male patients with cancer of buccal mucosa and 1194 gender- and age-matched controls. No significant correlation was observed between these two SNPs and the occurrence of OSCC in the case and control groups. While assessing the clinicopathological features, carriers of at least one minor allele of rs164966 (GA and GG) were less prone to develop lymph node metastasis (adjusted odds ratio [AOR], 0.666; 95% confidence interval [CI], 0.447-0.991; p=0.045) in comparison with homozygous carriers of the major allele (AA). Subsequent stratifying surveys revealed that this genetic association with nodal spread was seen only in cases who habitually chewed betel quid (AOR, 0.616; 95% CI, 0.386-0.985; p=0.042) or smoked cigarettes (AOR, 0.612; 95% CI, 0.393-0.953; p=0.029), but undetected in cases free of these main behavioral risks. Our results indicate an interactivity of LINC00312 rs164966 with lifestyle-related risks on modulating OSCC progression.

Convergent evolution of water-conducting cells in Marchantia recruited the ZHOUPI gene promoting cell wall reinforcement and programmed cell death.

A key adaptation of plants to life on land is the formation of water-conducting cells (WCCs) for efficient long-distance water transport. Based on morphological analyses it is thought that WCCs have evolved independently on multiple occasions. For example, WCCs have been lost in all but a few lineages of bryophytes but, strikingly, within the liverworts a derived group, the complex thalloids, has evolved a novel externalized water-conducting tissue composed of reinforced, hollow cells termed pegged rhizoids. Here, we show that pegged rhizoid differentiation in Marchantia polymorpha is controlled by orthologs of the ZHOUPI and ICE bHLH transcription factors required for endosperm cell death in Arabidopsis seeds. By contrast, pegged rhizoid development was not affected by disruption of MpNAC5, the Marchantia ortholog of the VND genes that control WCC formation in flowering plants. We characterize the rapid, genetically controlled programmed cell death process that pegged rhizoids undergo to terminate cellular differentiation and identify a corresponding upregulation of conserved putative plant cell death effector genes. Lastly, we show that ectopic expression of MpZOU1 increases production of pegged rhizoids and enhances drought tolerance. Our results support that pegged rhizoids evolved independently of other WCCs. We suggest that elements of the genetic control of developmental cell death are conserved throughout land plants and that the ZHOUPI/ICE regulatory module has been independently recruited to promote cell wall modification and programmed cell death in liverwort rhizoids and in the endosperm of flowering plant seed.

EF-24, a Curcumin Analog, Inhibits Cancer Cell Invasion in Human Nasopharyngeal Carcinoma through Transcriptional Suppression of Matrix Metalloproteinase-9 Gene Expression.

Cancer metastasis is a main cause of failure in treating subjects with nasopharyngeal carcinoma (NPC) and is frequently linked to high death rates. EF-24, an analog of curcumin, has exhibited many anti-cancer properties and enhanced bioavailability over curcumin. Nevertheless, the effects of EF-24 on the invasiveness of NPC are poorly understood. In this study, we demonstrated that EF-24 effectively inhibited TPA-induced motility and invasion responses of human NPC cells but elicited very limited cytotoxicity. In addition, the TPA-induced activity and expression of matrix metalloproteinase-9 (MMP-9), a crucial mediator of cancer dissemination, were found to be reduced in EF-24-treated cells. Our reporter assays revealed that such a reduction in MMP-9 expression by EF-24 was transcriptionally mediated by NF-κB via impeding its nuclear translocation. Further chromatin immunoprecipitation assays displayed that the EF-24 treatment decreased the TPA-induced interaction of NF-κB with the MMP-9 promoter in NPC cells. Moreover, EF-24 inhibited the activation of JNK in TPA-treated NPC cells, and the treatment of EF-24 together with a JNK inhibitor showed a synergistic effect on suppressing TPA-induced invasion responses and MMP-9 activities in NPC cells. Taken together, our data demonstrated that EF-24 restrained the invasiveness of NPC cells through the transcriptional suppression of MMP-9 gene expression, implicating the usefulness of curcumin or its analogs in controlling the spread of NPC.

Stomatal regulators are co-opted for seta development in the astomatous liverwort Marchantia polymorpha.

The evolution of special types of cells requires the acquisition of new gene regulatory networks controlled by transcription factors (TFs). In stomatous plants, a TF module formed by subfamilies Ia and IIIb basic helix-loop-helix TFs (Ia-IIIb bHLH) regulates stomatal formation; however, how this module evolved during land plant diversification remains unclear. Here we show that, in the astomatous liverwort Marchantia polymorpha, a Ia-IIIb bHLH module regulates the development of a unique sporophyte tissue, the seta, which is found in mosses and liverworts. The sole Ia bHLH gene, MpSETA, and a IIIb bHLH gene, MpICE2, regulate the cell division and/or differentiation of seta lineage cells. MpSETA can partially replace the stomatal function of Ia bHLH TFs in Arabidopsis thaliana, suggesting that a common regulatory mechanism underlies setal and stomatal formation. Our findings reveal the co-option of a Ia-IIIb bHLH TF module for regulating cell fate determination and/or cell division of distinct types of cells during land plant evolution.

Risk of Infertility in Males with Obstructive Sleep Apnea: A Nationwide, Population-Based, Nested Case-Control Study.

Obstructive sleep apnea (OSA) yields intermittent hypoxia, hypercapnia, and sleep fragmentation. OSA is associated with chronic medical conditions such as cardiovascular diseases, metabolic syndrome, and neurocognitive dysfunction. However, the risk of infertility in OSA remains unclear due to limited data and lack of long-term population-based studies. The study aims to assess the risk of infertility in obstructive sleep apnea (OSA) by means of a population-based cohort study. The data was utilized from the Taiwan National Health Insurance Research Database (NHIRD) to conduct a population-based cohort study (1997-2013). Compared with the Non-OSA group, the male with OSA and surgery group has the OR (odds ratio) of infertility of 2.70 (95% CI, 1.46-4.98, p = 0.0015), but no significance exists in females with OSA. When the data was stratified according to age and gender, some associations in the specific subgroups were significant. Respectively, males aged 20-35 years old and aged 35-50 years old with a history of OSA and surgery both had a positive association with infertility. (aOR: 3.19; 95% CI, 1.18-8.66, p = 0.0227; aOR: 2.57; 95% CI, 1.18-5.62 p = 0.0176). Male patients with OSA suffer from reduced fertility, but no significant difference was noted in females with OSA. The identification of OSA as a risk factor for male infertility will aid clinicians to optimize long-term medical care. Furthermore, more studies will be encouraged to clarify the effect of OSA on female fertility.

Lipocalin 2 Reduces MET Levels by Inhibiting MEK/ERK Signaling to Inhibit Nasopharyngeal Carcinoma Cell Migration.

Nasopharyngeal carcinoma (NPC) is the most common cancer that occurs in the nasopharynx, and it is difficult to detect early. The main cause of death of NPC patients is cancer metastasis. Lipocalin 2 (LCN2) has been shown to be involved in a variety of carcinogenesis processes. Here, we aimed to study the role of LCN2 in NPC cells and determine its underlying mechanism. We found that LCN2 was expressed differently in NPC cell lines, namely HONE-1, NPC-39, and NPC-BM. The down-regulation of LCN2 levels by siRNA targeting LCN2 (siLCN2) increased cell migration and invasion in HONE-1 cells, while the up-regulation of LCN2 levels by transfection with the LCN2 expression plasmid decreased cell migration and invasion in NPC-BM cells. Furthermore, LCN2 levels negatively regulated the phosphorylation of MEK/ERK pathways. The treatment of the specific MEK/ERK inhibitor, U0126, reduced cell migration in HONE-1 cells, whereas the treatment of tBHQ, an ERK activator, enhanced cell migration in NPC-BM cells. Based on the bioinformatics data, there was a moderately negative correlation between LCN2 and MET in metastatic NPC tissues (r = -0.5946, p = 0.0022). Indeed, the manipulation of LCN2 levels negatively regulated MET levels in these NPC cells. The treatment of U0126 reduced siLCN2-increased MET levels, while the treatment of tBHQ enhanced LCN2-enhanced MET levels. Interestingly, the down-regulation of MET levels by siMET further decreased siLCN2-enhanced MET levels and cell migration. Therefore, LCN2 inhibits NPC cell migration by reducing MET levels through MEK/ERK signaling.

Microbiota dysbiosis in odontogenic rhinosinusitis and its association with anaerobic bacteria.

Odontogenic rhinosinusitis is a subtype of rhinosinusitis associated with dental infection or dental procedures and has special bacteriologic features. Previous research on the bacteriologic features of odontogenic rhinosinusitis has mainly used culture-dependent methods. The variation of microbiota between odontogenic and nonodontogenic rhinosinusitis as well as the interplay between the involved bacteria have not been explored. Therefore, we enrolled eight odontogenic rhinosinusitis cases and twenty nonodontogenic rhinosinusitis cases to analyze bacterial microbiota through 16S rRNA sequencing. Significant differences were revealed by the Shannon diversity index (Wilcoxon test p = 0.0003) and PERMANOVA test based on weighted UniFrac distance (Wilcoxon test p = 0.001) between odontogenic and nonodontogenic samples. Anaerobic bacteria such as Porphyromonas, Fusobacterium, and Prevotella were significantly dominant in the odontogenic rhinosinusitis group. Remarkably, a correlation between different bacteria was also revealed by Pearson's correlation. Staphylococcus was highly positively associated with Corynebacterium, whereas Fusobacterium was highly negatively correlated with Prophyromonas. According to our results, the microbiota in odontogenic rhinosinusitis, predominantly anaerobic bacteria, was significantly different from that in nonodontogenic rhinosinusitis, and the interplay between specific bacteria may a major cause of this subtype of rhinosinusitis.

Risk of head and neck cancer in patients with peptic ulcers and the effect of Helicobacter pylori treatment.

It remained inconclusive whether patients with peptic ulcer disease had a higher risk of head and neck cancer (HNC). Therefore, we enrolled 109,360 patients with peptic ulcer disease and matched for age and sex with 218,720 controls from the Taiwan National Health Insurance Research Database between January 1, 1997 and December 31, 2013.The HNC incidence rate was 1.33-fold higher in the peptic ulcer group than in the control group (7.52 vs. 5.68 per 100,00 person-years; crude relative risk: 1.33; 95% confidence interval [CI]: 1.08-1.63) after > 6 years of follow-up. However, in the peptic ulcer subgroup with H. pylori treatment, HNC risk was not significantly different from that of the control group (crude relative risk: 1.12; 95% CI: 0.86-1.46). Moreover, the population with peptic ulcers had the highest risk of laryngeal and hypopharyngeal cancer (adjusted HR: 2.27 [95% CI: 1.16-4.44] and 2.00 [95% CI, 1.13-3.55]), respectively. This observational study suggested that peptic ulcer disease is associated with an increased incidence of laryngeal and hypopharyngeal cancer and H. pylori treatment may have a role in preventing HNC in patients with peptic ulcer disease.