Self-Assembly of Amphiphilic PDI and NDI Derivatives with Opposite Thermoresponsive Fluorescent Behaviors in Aqueous Solution.

This work presents a study of the thermally induced aggregation of perylene diimide (PDI) and naphthalene diimide (NDI) derivatives modified with oligo ethylene glycol (OEG) chains in aqueous solution. Water-soluble and flexible OEG side chains were introduced into the π-core of glutamate-modified NDI and PDI structures, and the aggregation process was modulated by heating or cooling in water. Interestingly, a rare opposite temperature response of fluorescent behavior from the two amphiphilic chromophores was revealed, in which the PDI exhibited fluorescent enhancement, while fluorescent quenching upon temperature increase was observed from the NDI assembly. The mechanism of thermally induced aggregation is clearly explained by studies with various spectroscopic techniques including UV-visible, fluorescence, 1H NMR, 2D NMR spectroscopy, and SEM observation as well as control experiments operated in DMSO solution. It is found that although similar J-aggregates were formed by both amphiphilic chromophores in aqueous solution, the temperature response of the aggregates to temperature was opposite. The degree of PDI aggregation decreased, while that of NDI increased upon temperature rising. This research paves a valuable way for understanding the complicated supramolecular behaviors of amphiphilic chromophores.

Heat-Set Supramolecular Hydrogelation by Regulating the Hydrophilic-Lipophilic Balance for a Tunable Circularly Polarized Luminescent Switch.

Heat-set supramolecular gels exhibited totally opposite phase behaviors of dissolution upon cooling and gelation on heating. They are commonly discovered by chance and their rational design remains a great challenge. Herein, a rational design strategy is proposed to realize heat-set supramolecular hydrogelation through regulation of the hydrophilic-lipophilic balance of the system. A newly synthesized amphiphile hydrogelator with pyrene embedded in its lipophilic terminal can self-assemble into a hydrogel through a heating and cooling cycle. However, the host-guest complex of the gelator and hydrophilic γ-cyclodextrin (γ-CyD) results in a sol at room temperature. Thus, heat-set hydrogelation is realized from the sol state in a controllable manner. Heat-set gelation mechanism is revealed by exploring critical heat-set supramolecular gelation and the related findings provide a general strategy for developing new functional molecular gels with tunable hydrophilic-lipophilic balance.

MYO5A overexpression promotes invasion and correlates with low lymphocyte infiltration in head and neck squamous carcinoma.

Head and neck squamous carcinoma (HNSC) poses a significant public health challenge due to its substantial morbidity. Nevertheless, despite advances in current treatments, the prognosis for HNSC remains unsatisfactory. To address this, single-cell RNA sequencing (RNA-seq) and bulk RNA-seq data combined with in vitro studies were conducted to examine the role of MYO5A (Myosin VA) in HNSC. Our investigation revealed an overexpression of MYO5A in HNSC that promotes HNSC migration in vitro. Remarkably, knockdown of MYO5A suppressed vimentin expression. Furthermore, analyzing the TCGA database evidenced that MYO5A is a risk factor for human papillomavirus positive (HPV+) HNSC (HR = 0.81, P < 0.001). In high MYO5A expression HNSC, there was a low count of tumor infiltrating lymphocytes (TIL), including activated CD4+ T cells, CD8+ T cells, and B cells. Of note, CD4+ T cells and B cells were positively associated with improved HPV+ HNSC outcomes. Correlation analysis demonstrated a decreased level of immunostimulators in high MYO5A-expressing HNSC. Collectively, these findings suggest that MYO5A may promote HNSC migration through vimentin and involve itself in the process of immune infiltration in HNSC, advancing the understanding of the mechanisms and treatment of HNSC.

Clinical efficacy in one-year treatment with Artemisia annua-SLIT drops in monosensitized and polysensitized individuals.

PURPOSE: Seasonal allergic rhinoconjunctivitis (SARC) caused by Artemisia seriously affects patients' quality of life in northern China. This study aimed to estimate further the efficacy and safety of a one-year course of Artemisia annua-sublingual immunotherapy (SLIT) on SARC patients. MATERIALS AND METHODS: This was an open-label, randomized, controlled, single-centre study involving 150 SARC patients induced by Artemisia, randomized to SLIT group (n = 75, SLIT along with pharmacotherapy) or control group (n = 75, pharmacotherapy only). According to the skin prick test (SPT) results, the SLIT group was divided into monosensitized and polysensitized groups to analyze the influence of sensitization status on the efficacy of Artemisia annua-SLIT. The clinical indicators of this study were total rhinoconjunctivitis symptom score (TRSS), total medication score (TMS), combined scores of medication and rhinoconjunctivitis symptom (CSMRS), and score of visual analog scale (VAS). Safety was evaluated by the occurrence of adverse events (AEs). Daily administration of the drops was recorded in diaries by the patients. RESULTS: After nearly one year of treatment and follow-ups, there was a significant decline in TRSS, TMS, CSMRS, and VAS from the baseline scores in the SLIT group (p < 0.001). However, as pollen counts increased in 2022, indicators above in the control group increased significantly during the peak pollen phase (PPP) in 2022 grass pollen season (GPS) compared to the baseline. Meanwhile, we found no significant difference in TRSS, TMS, CSMRS, and VAS between the monosensitized and polysensitized groups (p > 0.05). Moreover, the result indicated that the clinical improvement in TRSS, TMS, CSMRS, and VAS was still observed in polysensitized patients who were allergic to Artemisia pollen and sensitized to house dust mite (HDM) (n = 15) in PPP of 2022, compared to the baseline value (p < 0.001). CONCLUSION: Artemisia annua-SLIT was proven effective, tolerable and safe in patients with SARC after nearly one year of treatment, whether monosensitization or polysensitization.

Meta-Heuristic Device-Free Localization Algorithm under Multiple Path Effect.

In the scenario of device-free localization under multiple effects, the accuracy of localization based on compressed sensing theory is severely affected. Most existing localization techniques directly ignore multiple path effects. However, it is not practical to ignore the multiple path effect due to its high signal strength, which can provide localization information. In this paper, we formulate the sensing matrix optimization problem in compressed sensing for device-free localization scenarios based on multiple reflections. To solve this problem, we model it as a constrained combinatorial optimization problem and propose a hybrid meta-heuristic algorithm. First, smart reflection surfaces and virtual node models are used to construct the desired communication links. Second, we iteratively improve the properties of the measurement matrix by using K-means clustering to obtain reasonable thresholds, and use a meta-heuristic algorithm to optimize the sensing matrix. Finally, the simulation results show that the proposed method efficiently optimizes the sensing matrix and achieves fast and high-precision localization while conserving communication resources.

Efficacy and safety of Artemisia annua sublingual immunotherapy in patients with seasonal allergic rhinoconjunctivitis over two pollen seasons.

OBJECTIVE: This study investigates the efficacy and safety of sublingual immunotherapy (SLIT) with A. annua allergens in patients with seasonal allergic rhinoconjunctivitis over two pollen seasons. METHODS: Seventy patients with moderate-severe seasonal allergic rhinoconjunctivitis were divided evenly into the SLIT and control groups. The SLIT last from 3 months before the summer-autumn pollen season in 2021 till the end of the summer-autumn pollen season in 2022. The daily individual symptom score, total rhinoconjunctivitis symptom score (dTRSS), total medication score (dTMS), combined score of medication and rhinoconjunctivitis symptom (dCSMRS), visual analog scale (VAS) score, and adverse events (AEs) were evaluated. RESULTS: The average pollen concentration in 2022 was twice that previous two-year during the pollen season. Fifty-six patients completed treatments (SLIT group: 29, control group: 27). Compared with baseline, the individual symptoms, dTRSS, dTMS, dCSMRS, and VAS scores of SLIT group declined in 2021. After 16 months of SLIT, all efficacy indexes in 2022 were still lower than baseline and equivalent to those in 2021. In control group, the efficacy indexes in 2022 were higher than that in 2020 and 2021. The efficacy indexes of SLIT group were lower than those of control group in 2021 and 2022. SLIT is effective for both mono- and poly-sensitized patients. AEs incidence in SLIT group was 82.7% without severe AEs. CONCLUSIONS: The A. annua-SLIT can obtain efficacy and safety over two pollen seasons for patients with moderate-severe seasonal allergic rhinoconjunctivitis.

A terrified-sound stress causes cognitive impairment in female mice by impairing neuronal plasticity.

Stress is an important environmental factor affecting mental health that cannot be ignored. Moreover, due to the great physiological differences between males and females, the effects of stress may vary by sex. Previous studies have shown that terrified-sound stress, meaning exposed mice to the recorded vocalizations in response to the electric shock by their kind to induce psychological stress, can cause cognitive impairment in male. In the study, we investigated the effects of the terrified-sound stress on adult female mice. METHODS: 32 adults female C57BL/6 mice were randomly divided into control (n = 16) and stress group (n = 16). Sucrose preference test (SPT)was carried out to evaluate the depressive-like behavior. Using Open field test (OFT) to evaluate locomotor and exploratory alterations in mice. Spatial learning and memory ability were measured in Morris Water maze test (MWM), Golgi staining and western blotting showed dendritic remodeling after stress. In addition, serum hormone quantifications were performed by ELISA. RESULTS: we found the sucrose preference of stress group was significantly decreased (p < 0.05) compared with control group; the escape latency of the stress group was significantly prolonged (p < 0.05), the total swimming distance and the number of target crossings(p < 0.05) were significantly increased (p < 0.05) in MWM; Endocrine hormone, Testosterone (T) (p < 0.05), GnRH (p < 0.05), FSH and LH levels was decreased; Golgi staining and western blotting showed a significant decrease in dendritic arborization, spine density and synaptic plasticity related proteins PSD95 and BDNF in the stress group. CONCLUSION: Terrified-sound stress induced depressive-like behaviors, locomotor and exploratory alterations. And impaired cognitive by altering dendritic remodeling and the expression of synaptic plasticity-related proteins. However, females are resilient to terrified-sound stress from a hormonal point of view.

IGFL2-AS1 facilitates tongue squamous cell carcinoma progression via Wnt/ß-catenin signaling pathway.

OBJECTIVES: Tongue squamous cell carcinoma (TSCC) is the most common malignancy in oral cancer. Long noncoding RNAs (lncRNAs) are important regulators in cancer biology. In our present study, we investigated a novel lncRNA IGF-like family member 2 antisense RNA 1 (IGFL2-AS1) in TSCC. METHODS: RT-qPCR analyzed IGFL2-AS1 expression in TSCC cells. Functional assays assessed the impact of IGFL2-AS1 on TSCC cell proliferation, migration, and invasion. Western blot analyzed the protein levels of EMT-related markers. Mechanism assays analyzed the regulatory mechanism of IGFL2-AS1 in TSCC cells. In-vivo experiments were conducted to prove the role of IGFL2-AS1 in TSCC progression. RESULTS: IGFL2-AS1 was significantly up-regulated in TSCC cells and tissues, and IGFL2-AS1 knockdown inhibited cell proliferation, migration, invasion and EMT in TSCC. Moreover, IGFL2-AS1 functioned as a competing endogenous RNA (ceRNA) to sponge miR-1224-5p and thereby modulated SATB homeobox 1 (SATB1) expression. Additionally, SATB1 activated the Wnt/ß-catenin signaling pathway in TSCC cells and IGFL2-AS1 regulated the Wnt/ß-catenin signaling pathway and TSCC progression via elevating SATB1 expression. CONCLUSIONS: The data revealed that IGFL2-AS1 played a cancer promoting role in TSCC and may aid in exploring a brand new biomarker that might contribute to TSCC treatment.

Apigenin attenuates inflammatory response in allergic rhinitis mice by inhibiting the TLR4/MyD88/NF-κB signaling pathway.

BACKGROUND: Allergic rhinitis (AR) is an immunoglobulin E (IgE)-mediated immune inflammatory response that mainly affects the nasal mucosa. Currently, there is evidence that apigenin, as a flavonoid, has anti-allergic potential. MATERIAL/METHODS: In vitro, compound 48/80 and lipopolysaccharide (LPS) were used to induce mast cell activation and inflammation in HMC-1 cells. In vivo, ovalbumin (OVA) induced and stimulated AR in BALB/c mice. ELISA was used to detect the contents of ß-hexosaminidase, histamine, eosinophil cationic protein (ECP), OVA-specific IgE, IgG1, and IgG2a, inflammatory factors in cells and mouse serum. Cell viability and apoptosis were measured with MTT and flow cytometry. Toll like receptor 4 (TLR4)/myeloid differentiation factor88 (MyD88)/Nuclear transcription factor-κB (NF-κB) pathway-related proteins in cells and mouse nasal mucosa tissues were analyzed with Western blotting. The levels of Th1 (IFN-γ) and Th2 (IL-4, IL-5, and IL-13) cytokines and Th1 (T-bet) and Th2 (GATA-3) specific transcription factors were also assessed. The ratio of Th1 (CD4+ IFN-γ+ ) / Th2 (CD4+ IL-4+ ) cells in mouse peripheral blood mononuclear cells was evaluated by flow cytometry. RESULTS: Apigenin significantly inhibited compound 48/80-induced secretion of ß-hexosaminidase and histamine. Apigenin blocked LPS-induced decrease in cell viability and increase in cell apoptosis and inflammatory cytokine secretion by suppressing the activity of the TLR4/MyD88/NF-κB pathway. Apigenin treatment reduced the levels of OVA-specific IgE, IgG1 and IgG2a as well as ß-hexosaminidase, histamine and ECP levels in mouse serum. Moreover, administration with apigenin decreased Th2 cytokine and transcription factor levels and increased Th1 cytokine and transcription factor levels, and promoted the ratio of Th1/Th2 cells in AR mice. Additionally, apigenin significantly alleviated nasal symptoms and nasal eosinophil infiltration in AR mice. CONCLUSIONS: Apigenin alleviates the inflammatory response of allergic rhinitis by inhibiting the activity of the TLR4/MyD88/NF-κB signaling pathway.

Human Oral Keratinocytes Challenged by Streptococcus sanguinis and Porphyromonas gingivalis Differentially Affect the Chemotactic Activity of THP-1 Monocytes.

Periodontal diseases are initiated by the shift from microbe-host symbiosis to dysbiosis, and the disrupted host response predominantly contributes to tissue destruction. This study investigated whether and to what extent human oral keratinocytes (HOKs) challenged by a periodontal commensal or pathogen could differentially affect the chemotactic activity of THP-1 monocytes. A selected periodontal commensal (Streptococcus sanguinis ATCC 10556) and a pathogen (Porphyromonas gingivalis ATCC 33277) were cultured and inoculated, respectively, into the lower chamber of Transwell® Permeable Supports with HOKs and incubated for 2 h or 18 h at 37°C under appropriate cell growth conditions. HOKs alone served as the control for the transwell migration assay. Well-stained THP-1 monocytes were seeded in the top chamber of the device, incubated for 2 h and then collected from the lower well for quantitation of the migrated fluorescence-labeled cells by the FACSCalibur™ flow cytometer. The statistical significance was determined using one-way ANOVA. The HOKs challenged by S. sanguinis attracted a significantly higher number of THP-1 cell migration as compared with the control after 2 h or 18 h interaction (p < 0.01). By contrast, P. gingivalis-treated HOKs exhibited a markedly reduced chemotactic effect on THP-1 cells (p < 0.01, 2 h; p < 0.05, 18 h). There was no significant difference in THP-1 cell migration among the groups with either S. sanguinis or P. gingivalis alone. The current findings on P. gingivalis-HOKs interactions with resultant paralysis of THP-1 cell chemotaxis provide further evidence that the keystone periodontopathogen P. gingivalis can evade innate defense and contribute to periodontal pathogenesis.

The effect of VAV3 polymorphisms on thyroid cancer.

BACKGROUND: The incidence of thyroid cancer is rising rapidly in China, but there are few studies on the risk factors of thyroid cancer in the Chinese Han population. METHODS: We performed this case-control study of 510 patients and 509 controls to for determine the linkage of VAV3 variants (rs17019602, rs7521681, rs4915076, and rs1777451) with thyroid cancer susceptibility by computing the odds ratio (OR) and 95% confidence intervals (CI). Multi-factor dimension reduction (MDR) analysis was conducted to assess interaction of VAV3 genetic variants. RESULTS: We found that rs7521681 was remarkably related to a higher risk of thyroid cancer (OR = 1.74, p = 0.012), whereas rs4915076 (OR = 0.66, p = 0.001) significantly decreased thyroid cancer susceptibility. Stratified analyses showed that rs4915076 had a protective role in thyroid cancer in both ages >45 years (OR = 0.70, p = 0.017) and age ≤45 years (OR = 0.63, p = 0.007). Rs17019602 could increase the susceptibility of thyroid cancer in men (OR = 4.76, p = 0.049). Rs7521681 was related to an increased risk of thyroid cancer in women (OR = 1.97, p = 0.012). Rs4915076 could protect individuals from thyroid cancer both in men (OR = 0.60, p = 0.031) and women (OR = 0.68, p = 0.010). Moreover, rs4915076 was the best single-locus model to predict thyroid cancer. Interestingly, the interaction model of rs17019602, rs7521681, rs4915076, rs1777451, and age was a candidate gene-environment model. CONCLUSION: Our results indicated VAV3 variants were associated with thyroid cancer, which provides a new sight into etiology of thyroid cancer.

Tuning Rheological Behaviors of Supramolecular Aqueous Gels via Charge Transfer Interactions.

Rheological properties are critical for determining real applications of supramolecular gels in various fields. Correspondingly, the modulation of gel rheology will be very important for meeting real requirements. In this aspect, a few strategies were applied to tune the rheological behaviors of supramolecular gels, but some specific interactions like charge transfer (CT) interactions were less explored at the molecular level. Herein, we report a pyrene-containing derivative of diphenylalanine as a donor gelator and naphthalenediimide or 3,5-dinitrobenzene as matching acceptor molecules. It was found that the viscoelastic properties and strength of the original gel could be tuned through addition of different acceptor molecules to the original gel with changing the ratios of the selected acceptor molecules. As a result, storage modulus was continuously adjusted over a wide range from 190,000 to 50,000 Pa by CT interactions. Furthermore, the mechanism of the CT-induced change in rheological properties was understood and clarified through relevant techniques (e.g., UV-Vis, fluorescence, and FT-IR spectroscopy and TEM). The findings in this work would provide a novel strategy to modulate the rheological properties of supramolecular gels for adaption to broader fields of real applications.

Genetic polymorphisms in the PCNXL2 gene are risk factors for thyroid cancer in the Chinese population.

Background: Thyroid cancer is the most common endocrine malignancy and the fastest growing cancer worldwide. Thyroid cancer has the largest genetic component of all cancers. Previous genome-wide association studies indicated that genetic polymorphism in PCNXL2 is related to thyroid cancer susceptibility in European populations. This study aims to determine the influence of PCNXL2 polymorphisms on thyroid cancer risk in Chinese individuals. Methods: This case-control study identified four polymorphisms in PCNXL2 among 510 thyroid cancer cases and 509 healthy controls. The associations of PCNXL2 polymorphisms with thyroid cancer susceptibility were detected by calculating odds ratios. Multifactor dimensionality reduction was performed to detect the impact of SNP (single nucleotide polymorphism)-SNP interactions on the risk of thyroid cancer. Results: The study showed that rs10910660 in PCNXL2 was related to thyroid cancer susceptibility. Rs12129938 played a protective role in thyroid cancer susceptibility. Stratification analysis indicated that rs10910660 increased thyroid cancer risk at age >45 years. Rs12129938 enhanced susceptibility to thyroid cancer at age >45 years, while this SNP decreased thyroid cancer risk at age ≤45 years. Rs4649295 was associated with lower susceptibility to thyroid cancer at age ≤45 years. An association was observed between rs6424270 and rs12129938 with decreased susceptibility to thyroid cancer in women. Rs10910660 was related to thyroid cancer risk in men. The combination of rs6424270, rs10910660, rs12129938 and rs4649295 was the best model to predict thyroid cancer. Conclusion: This study suggests that PCNXL2 polymorphisms are risk factors for thyroid cancer in the Chinese population.

Long non-coding RNA SNHG16, binding with miR-106b-5p, promoted cell apoptosis and inflammation in allergic rhinitis by up-regulating leukemia inhibitory factor to activate the JAK1/STAT3 signaling pathway.

Allergic rhinitis (AR) is a type I hypersensitive disease. Long non-coding RNA (lncRNA) SNHG16 acts as an oncogene in a variety of tumors and promotes the occurrence of inflammation in many inflammatory diseases. The study aims to investigate the expression of SNHG16 and its potential biological functions in AR. RT-qPCR results showed that the expression of SNHG16 in AR was up-regulated. The AR cell model was constructed by stimulating primary nasal mucosal epithelial cells from AR patients with IL-13. After knocking down the expression of lncRNA SNHG16, cell apoptosis was detected by flow cytometry, and the expression of inflammatory factors was detected by ELISA. The results showed that SNHG16 promoted cell apoptosis and inflammation. Then, bioinformatics analysis was used to screen miRNAs bound with SNHG16. Luciferase reporter gene assay and RNA pull-down experiment were used to verify the relationship. We found that the expression of miR-106b-5p was down-regulated and leukemia inhibitory factor (LIF) expression was up-regulated in the AR cell model. The expression of phospho-Janus kinase 1 and p-signal transducer and activator of transcription 3 (STAT3) were detected by Western blotting. Silencing the expression of LIF could inhibit the activity of JAK1/STAT3 pathway and further inhibit cell apoptosis and the occurrence of inflammation. Then transfected SNHG16 shRNA alone or together with miR-106b-5p antagomir into the AR cell model, we found that silencing the expression of SNHG16 down-regulated the expression of LIF and inhibited the activity of the JAK1/STAT3 pathway, cell apoptosis, and inflammation. However, miR-106b-5p antagomir weakened its inhibitory effects. The role of SNHG16 in AR was further verified by the ovalbumin-induced AR mouse model in vivo. In conclusion, SNHG16 up-regulates LIF expression by binding with miR-106b-5p, thus promoting the activity of JAK1/STAT3 pathway, and promoting the development of AR. These results provide new targets for the treatment of AR and may help reduce the damage caused by AR.

IL-1RN gene polymorphisms reduces thyroid cancer risk in Chinese Han population.

The purpose of this study was to investigate the effect of IL-1RN polymorphisms on thyroid cancer (TC) risk in Han population. Genotypes of four single nucleotide polymorphisms (SNPs) (rs17042888, rs928940, rs3181052, and rs452204) were analyzed by Agena MassARRAY. Meanwhile, we used the logistic regression to calculate the odds ratios (ORs) and 95% confidence intervals (CIs), and significant differences were evaluated by t test and χ2 test. Findings found that allele "G" of rs452204 and rs3181052 in interleukin-1 receptor antagonist (IL-1RN) reduced the risk of TC. (OR = 0.72, 95% CI = 0.55-0.94, p = .017; OR = 0.73, 95% CI = 0.56-0.94, p = .017, respectively). Hierarchical analysis indicated that three SNPs (rs17042888, rs3181052, and rs452204) significantly reduced the risk of TC among females or individuals older than 48 years (p < .05). Our findings indicate that IL-1RN polymorphisms may contribute to a protective role against TC risk.

IL-1B rs2853550 polymorphism contributes to esophageal cancer susceptibility in Chinese Han population of Northwest China.

BACKGROUND: Esophageal cancer (EC) is one of the most common human cancers, with a particularly aggressive behavior and increased incidence worldwide. The aim of this study was to assess the associations of single-nucleotide polymorphisms (SNPs) in IL-1B with the risk of EC in a northwest Chinese Han population. METHODS: In order to evaluate the correlations between IL-1B polymorphisms and EC risk, an Agena MassARRAY platform was used to determine the genotype of the candidate SNPs among 384 EC patients and 499 controls. The associations between IL-1B variants and EC risk were examined using logistic regression analysis with adjustment for gender and age. Haplotype construction and analysis were performed to detect the potential associations between haplotypes within IL-1B and EC susceptibility. Additionally, bioinformatics databases were used for gene expression analysis and SNP functional prediction. RESULTS: A significant relationship was found between IL-1B rs2853550 and an increased risk of EC in the allele model [odds ratio (OR) = 1.38, 95% confidence interval (95% CI): 1.01-1.89, p = 0.041), the codominant model (A/G, OR = 1.63, 95% CI: 1.10-2.42, p = 0.011), and the dominant model (OR = 1.49, 95% CI: 1.02-2.18, p = 0.041). Functional analysis revealed the potential effects of rs2853550, which further reinforced its influence on EC susceptibility. However, there were no statistically significant differences for other SNPs or haplotypes between EC cases and healthy controls. Expression analysis conducted with dataset indicated that the expression level of IL-1B was higher in EC cases than that in normal samples. CONCLUSIONS: This study demonstrated that rs2853550 in IL-1B might increase EC susceptibility in the Chinese Han population of Northwest China.

IL1A & IL1B genetic polymorphisms are risk factors for thyroid cancer in a Chinese Han population.

INTRODUCTION: Thyroid carcinoma accounts for a large proportion of endocrine neoplasia, and the relationship between inflammation and thyroid cancer has been previously validated. IL-1α (Interleukin 1 alpha) and IL-1ß (Interleukin 1 beta), encoded by IL1A and IL1B, respectively, are implicated in numerous inflammatory responses and in tumor progression. The objective of this research was to assess the association of genetic polymorphisms of IL1A and IL1B with the risk of thyroid cancer in a Chinese Han population. MATERIALS AND METHODS: Genotypes of the 12 candidate SNPs in IL1A and IL1B were identified among 208 thyroid cancer patients and 279 healthy controls using an Agena MassARRY method. Genetic model analysis was carried out to evaluate the significant links between the variants and thyroid cancer risk. HaploReg v4.1 and the GTEx database were used for SNP functional annotation and expression quantitative trait loci (eQTL) analysis, respectively. RESULTS: Significant associations were detected between IL1A rs3783521 and an increased thyroid cancer risk in our study population (p < 0.05). IL1A rs3783546 and rs3783521 were associated with an increased cancer risk in men, and IL1B rs3136558 and rs1143623 were associated with an decreased cancer risk in women. Meanwhile, rs3783550, rs3783546, rs1609682, and rs3783521 in IL1A were identified as biomarkers of risk among individuals aged ≤48 years. Rs3136558 and rs1143623 in the IL1B gene showed strong correlations with a susceptibility to thyroid cancer among individuals aged >48 years. Additionally, bioinformatics and eQTLs analysis also provided supporting evidence for the effects of the SNPs on gene regulation. CONCLUSIONS: Our study is the first to report that IL1A and IL1B polymorphisms are risk factors for thyroid carcinoma in a Chinese Han population.

Polymorphisms of the Highly Expressed IL-6 Gene in the Papillary Thyroid Cancer Susceptibility Among Chinese.

BACKGROUND: Papillary thyroid cancer (PTC) is the cardinal histologic type of thyroid cancer, which is the most prevalent kind of endocrine malignancy. The expression of IL-6 is found higher in thyroid carcinoma (THCA) samples than paired normal tissues based on The Cancer Genome Atlas (TCGA) and Genotype-Tissue expression (GTEx) database. In this study, we aimed to investigate the association between interleukin-6 (IL-6) polymorphisms and the PTC risk. METHODS: A case-control study was designed using the following data: 241 PTC patients and 463 healthy controls. Five single nucleotide polymorphisms (SNPs) in IL-6 were selected and genotyped using Agena MassARRAY technology. RESULTS: Our results revealed that SNP rs1800796 was associated with an increased PTC risk in co-dominant model (p = 0.042) and dominant model (p = 0.027). Rs1524107 was also a risk factor for PTC susceptibility in co-dominant model (p = 0.003), dominant model (p = 0.002) and log-additive model (p = 0.044). Moreover, rs2066992 significantly increased the PTC risk in co-dominant model and dominant model (p = 0.011, p = 0.009, respectively). Additionally, rs2069837 variant elevated the PTC risk based on dominant model (p = 0.041). In silico analysis, GTEx results for rs1800796, rs1524107 and rs2066992 variants are known to be associated with IL-6 gene expression. Using HaploReg, we found rs1800796, rs1524107 and rs2066992 in LD with functional importance. CONCLUSION: Our study indicates that IL-6 variants may be a risk factor involved in the pathogenesis and development of PTC.

Knockdown of FOXJ1 inhibits the proliferation, migration, invasion, and glycolysis in laryngeal squamous cell carcinoma cells.

Forkhead box (FOX) proteins are a large family of transcription factors that are involved in multiple biological processes. FOXJ1, a member of the FOX family, has been found to participate in tumorigenesis. However, the role of FOXJ1 in laryngeal squamous cell carcinoma (LSCC) is still unclear. The aim of the present study was to explore the potential roles of FOXJ1 in LSCC. Our results showed that FOXJ1 was overexpressed in LSCC tissues and cell lines. Then the small interfering RNA targeting FOXJ1 (FOXJ1-siRNA) or control siRNA was transfected into TU-177 and AMC-HN-8 cells to knockdown FOXJ1. Cell Counting Kit-8 assay showed that knockdown of FOXJ1 inhibited the proliferation of LSCC cells. Transwell assay revealed that FOXJ1-siRNA-transfected cells showed significant reduction in cell migration and invasion compared to the cells transfected with control siRNA. FOXJ1 knockdown suppressed glycolysis in LSCC cells, which was illustrated by the reduced glucose consumption and lactate production. In addition, FOXJ1 knockdown inhibited the activation of the Wnt/ß-catenin pathway, and the LiCl treatment mitigated the inhibitory effects of FOXJ1-siRNA on cell proliferation, migration, invasion, and glycolysis. These findings indicated that FOXJ1-siRNA executed its functions via suppressing the activation of the Wnt/ß-catenin pathway.