Effect of blood lead levels on periodontitis in American adults: a cross-sectional analysis from the national health and nutrition examination survey.

BACKGROUND: The primary objective of this study was to assess the impact of blood lead levels on the development and progression of periodontitis. METHODS: This study included 8600 participants from the National Nutrition and Health Examination Survey conducted the United States between 2009 and 2014. The exposure variable was the blood lead level, while the outcome variable was periodontitis. To evaluate the relationship between the blood lead level and periodontitis, a multivariate logistic regression model was used. RESULTS: A positive association was observed between blood lead levels and the risk of periodontitis in Model 1 (OR = 7.04, 95% CI = 5.95-8.31). After adjusting for age (continuous), sex, ethnicity, and BMI (continuous) in Model 2, the significant association between blood lead levels and periodontitis risk remained evident (OR = 3.06, 95% CI: 2.54-3.70). Consequently, even after comprehensive adjustment for potential confounding factors in Model 3, the robust association between blood lead levels and periodontitis risk persisted (OR = 2.08, 95% CI = 1.67-2.60). When considering the serum lead concentration as a categorical variable and after adjusting for potential confounders in Model 3, we observed that the odds ratios (ORs) of periodontitis in the T2 (0.94 µg/dL-1.60 µg/dL) and T3 (lead ≥ 1.60 µg/dL) groups increased from 1.27 (OR = 1.27, 95% CI: 1.11-1.44) to 1.57 (OR = 1.57, 95% CI: 1.36-1.81) compared to T1 group. Subgroup analysis revealed no effect modifiers. CONCLUSIONS: Our main findings suggest that there is no safe range of blood lead levels regarding periodontitis risk and that increasing blood lead levels can significantly increase the prevalence of periodontitis.

SURVS: A Swin-Unet and game theory-based unsupervised segmentation method for retinal vessel.

Medical images, especially intricate vascular structures, are costly and time-consuming to annotate manually. It is beneficial to investigate an unsupervised method for vessel segmentation, one that circumvents the manual annotation yet remains valuable for disease detection. In this study, we design an unsupervised retinal vessel segmentation model based on the Swin-Unet framework and game theory. First, we construct two extreme pseudo-mapping functions by changing the contrast of the images and obtain their corresponding pseudo-masks based the on binary segmentation method and mathematical morphology, then we prove that there exists a mapping function between pseudo-mappings such that its corresponding mask is closest to the ground true mask. To acquire the best-predicted mask, based on which, we second develop a model based on the Swin-Unet frame to solve the optimal mapping function, and introduce an Image Colorization proxy task to assist the learning of pixel-level feature representations. Third, since to the instability of two pseudo-masks, the predicted mask will inevitably have errors, inspired by the two-player, non-zero-sum, non-cooperative Neighbor's Collision game in game theory, a game filter is proposed in this paper to reduce the errors in the final predicted mask. Finally, we verify the effectiveness of the presented unsupervised retinal vessel segmentation model on DRIVE, STARE and CHASE_DB1 datasets, and extensive experiments show that has obvious advantages over image segmentation and conventional unsupervised models.

Effects of 2,2'-Azobis(2-methylpropionamidine) Dihydrochloride Stress on the Gel Properties of Duck Myofibrillar Protein Isolate.

The aim of this study was to investigate the biochemical properties and gel-forming capacity of duck myofibrillar proteins under the effects of 2,2'-azobis(2-methylpropionamidine) dihydrochloride (AAPH)-mediated oxidation. Duck myofibrillar proteins were extracted and treated with different concentrations of AAPH solutions (0, 1, 3, 5, 10 mmol/L) and then analysed for carbonyl content, dynamic rheology, protein profiles and gel-forming properties (colour, water holding capacity, gel strength and microstructure). The results showed that with increasing AAPH concentration, the carbonyl content of the proteins exhibited an increasing trend (p < 0.05); SDS-PAGE pattern changes indicated that moderate oxidation (3 mmol/L AAPH) induced myosin aggregation via covalent bonds including disulfide, enhanced protein-protein interactions, and thus affected the gel strength of the DMPs' heat-induced gels. However, high oxidation (5 and 10 mmol/L AAPH) led to the partial degradation of the myosin heavy chain (MHC) isoforms, as evidenced by lower storage modulus and irregular microstructures, which significantly reduced gelation ability. These results suggest that the internal relationship between alkylperoxyl radical-induced oxidation should be taken into account in the processing of duck meat, as mild protein oxidation is conducive to improving gel quality.

25-hydroxyvitamin D levels in children of different ages and with varying degrees of Helicobacter pylori infection and immunological features.

Background: Helicobacter pylori (HP) is a major cause of upper digestive tract diseases. However, the relationship between HP infection and 25-hydroxyvitamin D [25(OH)D] levels in children has not been fully elucidated. This study investigated the levels of 25(OH)D in children of different ages and with varying degrees of HP infection and immunological features as well as the correlations between 25(OH)D levels in children infected with HP and their ages and degrees of infection. Materials and methods: Ninety-four children who underwent upper digestive endoscopy were divided into an HP-positive group without peptic ulcers (Group A), an HP-positive group with peptic ulcers (Group B) and an HP-negative control group (Group C). The serum levels of 25(OH)D and immunoglobulin and the percentages of lymphocyte subsets were determined. HP colonization, the degree of inflammation, and the degree of activity were further evaluated by HE staining and immunohistochemical staining in gastric mucosal biopsy. Results: The 25(OH)D level of the HP-positive groups (50.93 ± 16.51 nmol/L) was significantly lower than that of the HP-negative group (62.89 ± 19.18 nmol/L). The 25(OH)D level of Group B (47.79 ± 14.79 nmol/L) was lower than that of Group A (51.53 ± 17.05 nmol/L) and was significantly lower than that of Group C (62.89 ± 19.18 nmol/L). The 25(OH)D level decreased with increasing age, and there was a significant difference between Group C subjects who were ≤5 years old and those who were aged 6-9 years and ≥10 years. The 25(OH)D level was negatively correlated with HP colonization (r = -0.411, P < 0.01) and the degree of inflammation (r = -0.456, P < 0.01). The percentages of lymphocyte subsets and immunoglobulin levels among Groups A, B and C were not significantly different. Conclusions: The 25(OH)D level was negatively correlated with HP colonization and the degree of inflammation. As the age of the children increased, the level of 25(OH)D decreased, and the susceptibility to HP infection increased.

Potential of Secondary Metabolites of Diaporthe Species Associated with Terrestrial and Marine Origins.

Diaporthe species produce versatile secondary metabolites (SMs), including terpenoids, fatty acids, polyketides, steroids, and alkaloids. These structurally diverse SMs exhibit a wide range of biological activities, including cytotoxic, antifungal, antibacterial, antiviral, antioxidant, anti-inflammatory, and phytotoxic activities, which could be exploited in the medical, agricultural, and other modern industries. This review comprehensively covers the production and biological potencies of isolated natural products from the genus Diaporthe associated with terrestrial and marine origins. A total of 275 SMs have been summarized from terrestrial (153; 55%) and marine (110; 41%) origins during the last twelve years, and 12 (4%) compounds are common to both environments. All secondary metabolites are categorized predominantly on the basis of their bioactivities (cytotoxic, antibacterial, antifungal, and miscellaneous activity). Overall, 134 bioactive compounds were isolated from terrestrial (92; 55%) and marine (42; 34%) origins, but about half the compounds did not report any kind of activity. The antiSMASH results suggested that Diaporthe strains are capable of encoding a wide range of SMs and have tremendous biosynthetic potential for new SMs. This study will be useful for future research on drug discovery from terrestrial and marine natural products.

Periodontal disease is associated with the risk of cardiovascular disease independent of sex: A meta-analysis.

Objectives: Studies have established a link between periodontal disease and cardiovascular disease (CVD), but it is unclear whether there is a sex difference in their association. Methods: The PubMed, Embase, and Cochrane databases were searched until June, 21 2022. Cardiovascular outcomes included any CVD, myocardial infarction (MI), coronary heart disease (CHD), or stroke. Studies reported the prevalence of CVD in patients with periodontal disease and the relationship between periodontal disease and CVD. The study is registered with PROSPERO (CRD42022333663). The level of evidence and recommendations is assessed by the Grading of Recommendations for Assessment, Development and Evaluation (GRADE). Results: Twenty-six studies were included. In patients with periodontal disease, the prevalence of CVD was 7.2% [9 studies; 95% confidence interval (CI): 2.7-13.6%], and prevalence for CHD, hypertension, stroke, and heart failure was 6.6, 25.3, 1, and 1.1%, respectively. There was a significant association between periodontal disease and CVD in men [odds ratio (OR) = 1.22; 95% CI: 1.12-1.34] and women (OR = 1.11; 95% CI: 1.05-1.17), with no significant sex difference (P > 0.05). Conclusion: Cardiovascular disease is relatively common in patients with periodontal disease, and an increased risk of CVD is associated with periodontal disease independent of sex. Interventions targeting periodontal disease may be beneficial for CVD. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022333663.

COVID-19 diagnosis utilizing wavelet-based contrastive learning with chest CT images.

The pandemic caused by the coronavirus disease 2019 (COVID-19) has continuously wreaked havoc on human health. Computer-aided diagnosis (CAD) system based on chest computed tomography (CT) has been a hotspot option for COVID-19 diagnosis. However, due to the high cost of data annotation in the medical field, it happens that the number of unannotated data is much larger than the annotated data. Meanwhile, having a highly accurate CAD system always requires a large amount of labeled data training. To solve this problem while meeting the needs, this paper presents an automated and accurate COVID-19 diagnosis system using few labeled CT images. The overall framework of this system is based on the self-supervised contrastive learning (SSCL). Based on the framework, our enhancement of our system can be summarized as follows. 1) We integrated a two-dimensional discrete wavelet transform with contrastive learning to fully use all the features from the images. 2) We use the recently proposed COVID-Net as the encoder, with a redesign to target the specificity of the task and learning efficiency. 3) A new pretraining strategy based on contrastive learning is applied for broader generalization ability. 4) An additional auxiliary task is exerted to promote performance during classification. The final experimental result of our system attained 93.55%, 91.59%, 96.92% and 94.18% for accuracy, recall, precision, and F1-score respectively. By comparing results with the existing schemes, we demonstrate the performance enhancement and superiority of our proposed system.

Exploring Gut Microbiome in Predicting the Efficacy of Immunotherapy in Non-Small Cell Lung Cancer.

We performed various analyses on the taxonomic and functional features of the gut microbiome from NSCLC patients treated with immunotherapy to establish a model that may predict whether a patient will benefit from immunotherapy. We collected 65 published whole metagenome shotgun sequencing samples along with 14 samples from our previous study. We systematically studied the taxonomical characteristics of the dataset and used both the random forest (RF) and the multilayer perceptron (MLP) neural network models to predict patients with progression-free survival (PFS) above 6 months versus those below 3 months. Our results showed that the RF classifier achieved the highest F-score (85.2%) and the area under the receiver operating characteristic curve (AUC) (95%) using the protein families (Pfam) profile, and the MLP neural network classifier achieved a 99.9% F-score and 100% AUC using the same Pfam profile. When applying the model trained in the Pfam profile directly to predict the treatment response, we found that both trained RF and MLP classifiers significantly outperformed the stochastic predictor in F-score. Our results suggested that such a predictive model based on functional (e.g., Pfam) rather than taxonomic profile might be clinically useful to predict whether an NSCLC patient will benefit from immunotherapy, as both the F-score and AUC of functional profile outperform that of taxonomic profile. In addition, our model suggested that interactive biological processes such as methanogenesis, one-carbon, and amino acid metabolism might be important in regulating the immunotherapy response that warrants further investigation.

A self-supervised COVID-19 CT recognition system with multiple regularizations.

The diagnosis of Coronavirus Disease 2019 (COVID-19) exploiting machine learning algorithms based on chest computed tomography (CT) images has become an important technology. Though many excellent computer-aided methods leveraging CT images have been designed, they do not possess sufficiently high recognition accuracy. Besides, these methods entail vast amounts of training data, which might be difficult to be satisfied in some real-world applications. To address these two issues, this paper proposes a novel COVID-19 recognition system based on CT images, which has high recognition accuracy, while only requiring a small amount of training data. Specifically, the system possesses the following three improvements: 1) Data: a novel redesigned BCELoss that incorporates Label Smoothing, Focal Loss, and Label Weighting Regularization (LSFLLW-R) technique for optimizing the solution space and preventing overfitting, 2) Model: a backbone network processed by two-phase contrastive self-supervised learning for classifying multiple labels, and 3) Method: a decision-fusing ensemble learning method for getting a more stable system, with balanced metric values. Our proposed system is evaluated on the small-scale expanded COVID-CT dataset, achieving an accuracy of 94.3%, a precision of 94.1%, a recall (sensitivity) of 93.4%, an F1-score of 94.7%, and an Area Under the Curve (AUC) of 98.9%, for COVID-19 diagnosis, respectively. These experimental results verify that our system can not only identify pathological locations effectively, but also achieve better performance in terms of accuracy, generalizability, and stability, compared with several other state-of-the-art COVID-19 diagnosis methods.

Latent adversarial regularized autoencoder for high-dimensional probabilistic time series prediction.

Many practical applications require probabilistic prediction of time series to model the distribution on future horizons. With ever-increasing dimensions, much effort has been invested into developing methods that often make an assumption about the independence between time series. Consequently, the probabilistic prediction in high-dimensional environments has become an essential topic with significant challenges. In this paper, we propose a novel probabilistic model called latent adversarial regularized autoencoder, abbreviated as TimeLAR, specifically for high-dimensional multivariate Time Series Prediction (TSP). It integrates the flexibility of Generative Adversarial Networks (GANs) and the capability of autoencoders in extracting higher-level non-linear features. Through flexible autoencoder mapping, TimeLAR learns cross-series relationships and encodes this global information into several latent variables. We design a modified Transformer for these latent variables to capture global temporal patterns and infer latent space prediction distributions, where only one step is required to output multi-step predictions. Furthermore, we employ the GAN to further refine the performance of latent space predictions, by using a discriminator to guide the training of the autoencoder and the Transformer in an adversarial process. Finally, complex distributions of multivariate time series data can be modeled by the non-linear decoder of the autoencoder. The effectiveness of TimeLAR is empirically underpinned by extensive experiments conducted on five real-world high-dimensional time series datasets in the fields of transportation, electricity, and web page views.

CLINICAL EFFICACY OF PROBIOTICS AS AN ADJUNCTIVE THERAPY TO SCALING AND ROOT PLANNING IN THE MANAGEMENT OF PERIODONTITIS: A SYSTEMATIC REVIEW AND META-ANALYSIS OF RANDOMIZED CONTROLLED TRAILS.

OBJECTIVES: To evaluate the efficacy of probiotics as an adjunctive therapy to scaling and root planning treatment (SRP) in the management of periodontitis. METHODS: PubMed, Embase, Web of science, SCOPUS and the Cochrane library were systematically searched to identify eligible studies. Stata 12.0 software was used to calculate the weighted mean differences (WMD) and 95% confidential interval (CI). The primary outcomes were clinical attachment level (CAL), probing pocket depth (PPD) and bleeding on probing (BOP). RESULTS: Twenty-four randomized controlled trials (RCT) were included in the meta-analysis. The pooled results showed CAL gain (WMD: 0.20, 95% CI 0.09 to 0.31), PPD reduction (WMD: -0.31, 95% CI -0.52 to -0.10) and BOP reduction (WMD: -2.98, 95% CI -4.70 to -1.26) in the SRP+ probiotics group were significantly improved compared to control group at 3 months follow-up, but no significant difference was observed at 6 months. In addition, the probiotics administration could improve Plaque index (WMD: -0.30, 95% CI -0.59 to -0.05) and Gingival index (WMD: -0.46, 95% CI -0.71 to -0.21) at short term. CONCLUSIONS: The results support the clinical efficacy of probiotics as an adjunctive therapy to SRP in the management of periodontitis at least 3 months follow-up. Within the limits of the evidence, the long-term efficacy needs to further confirm.

Prospective correlation between the patient microbiome with response to and development of immune-mediated adverse effects to immunotherapy in lung cancer.

BACKGROUND: Though the gut microbiome has been associated with efficacy of immunotherapy (ICI) in certain cancers, similar findings have not been identified for microbiomes from other body sites and their correlation to treatment response and immune related adverse events (irAEs) in lung cancer (LC) patients receiving ICIs. METHODS: We designed a prospective cohort study conducted from 2018 to 2020 at a single-center academic institution to assess for correlations between the microbiome in various body sites with treatment response and development of irAEs in LC patients treated with ICIs. Patients must have had measurable disease, ECOG 0-2, and good organ function to be included. Data was collected for analysis from January 2019 to October 2020. Patients with histopathologically confirmed, advanced/metastatic LC planned to undergo immunotherapy-based treatment were enrolled between September 2018 and June 2019. Nasal, buccal and gut microbiome samples were obtained prior to initiation of immunotherapy +/- chemotherapy, at development of adverse events (irAEs), and at improvement of irAEs to grade 1 or less. RESULTS: Thirty-seven patients were enrolled, and 34 patients were evaluable for this report. 32 healthy controls (HC) from the same geographic region were included to compare baseline gut microbiota. Compared to HC, LC gut microbiota exhibited significantly lower α-diversity. The gut microbiome of patients who did not suffer irAEs were found to have relative enrichment of Bifidobacterium (p = 0.001) and Desulfovibrio (p = 0.0002). Responders to combined chemoimmunotherapy exhibited increased Clostridiales (p = 0.018) but reduced Rikenellaceae (p = 0.016). In responders to chemoimmunotherapy we also observed enrichment of Finegoldia in nasal microbiome, and increased Megasphaera but reduced Actinobacillus in buccal samples. Longitudinal samples exhibited a trend of α-diversity and certain microbial changes during the development and resolution of irAEs. CONCLUSIONS: This pilot study identifies significant differences in the gut microbiome between HC and LC patients, and their correlation to treatment response and irAEs in LC. In addition, it suggests potential predictive utility in nasal and buccal microbiomes, warranting further validation with a larger cohort and mechanistic dissection using preclinical models. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03688347 . Retrospectively registered 09/28/2018.

Relating Gut Microbiome and Its Modulating Factors to Immunotherapy in Solid Tumors: A Systematic Review.

Background: Gut microbiome is proved to affect the activity of immunotherapy in certain tumors. However, little is known if there is universal impact on both the treatment response and adverse effects (AEs) of immune checkpoint inhibitors (ICIs) across multiple solid tumors, and whether such impact can be modulated by common gut microbiome modifiers, such as antibiotics and diet. Methods: A systematic search in PubMed followed by stringent manual review were performed to identify clinical cohort studies that evaluated the relevance of gut microbiome to ICIs (response and/or AEs, 12 studies), or association of antibiotics with ICIs (17 studies), or impact of diet on gut microbiome (16 studies). Only original studies published in English before April 1st, 2020 were used. Qualified studies identified in the reference were also included. Results: At the phylum level, patients who had enriched abundance in Firmicutes and Verrucomicrobia almost universally had better response from ICIs, whereas those who were enriched in Proteobacteria universally presented with unfavorable outcome. Mixed correlations were observed for Bacteroidetes in relating to treatment response. Regarding the AEs, Firmicutes correlated to higher incidence whereas Bacteroidetes were clearly associated with less occurrence. Interestingly, across various solid tumors, majority of the studies suggested a negative association of antibiotic use with clinical response from ICIs, especially within 1-2 month prior to the initiation of ICIs. Finally, we observed a significant correlation of plant-based diet in relating to the enrichment of "ICI-favoring" gut microbiome (P = 0.0476). Conclusions: Gut microbiome may serve as a novel modifiable biomarker for both the treatment response and AEs of ICIs across various solid tumors. Further study is needed to understand the underlying mechanism, minimize the negative impact of antibiotics on ICIs, and gain insight regarding the role of diet so that this important lifestyle factor can be harnessed to improve the therapeutic outcomes of cancer immunotherapy partly through its impact on gut microbiome.

The effect of denture restoration and dental implant restoration in the treatment of dentition defect: a systematic review and meta-analysis.

BACKGROUND: Dentition defect is a common symptom in clinical dental patients. This study compared the clinical effects of denture restoration and dental implant restoration in the treatment of dentition defects through meta-analysis. METHODS: Data retrieval was conducted through the PubMed, Web of Science, Embase, CNKI, and Wanfang databases. A total of 479 related literatures published in English or Chinese from 2013 to 2020 were included. Literature screening, data extraction and comprehensive evaluation, and analysis by meta-analysis was performed by 3 authors. RESULTS: A total of 17 studies and 1,459 patients were included. Among the 17 studies, the effective rate of treatment between the two groups was compared and the experimental group rate was significantly higher than that of the control group [odds ratio (OR) =6.149, 95% confidence interval (CI): 4.103-9.215, P<0.001]; the mastication function score was compared, and was higher in the experimental group than in the control group [standardized mean difference (SMD) =1.632, 95% CI: 1.039-2.224, P<0.001]; the retention function score was compared, and was higher in the experimental group than in the control group (SMD =1.775, 95% CI: 1.095-2.455), P<0.001); the aesthetics score was also compared, and was higher in the experimental group than in the control group (SMD =1.300, 95% CI: 0.499-2.100, P=0.001). Among 17 studies, 15 compared the comfort score, which was higher in the experimental group than in the control group (SMD =1.357, 95% CI: 0.455-2.258, P=0.003). CONCLUSIONS: Compared with denture restoration, dental implant restoration is more effective in the treatment of dentition defect with a higher comprehensive score of functional restoration.

Long Non-Coding RNA NKILA Reduces Oral Squamous Cell Carcinoma Development Through the NF-KappaB Signaling Pathway.

OBJECTIVE: Emerging studies have identified that long non-coding RNAs (lncRNAs) play critical roles in cancer development. This study aims to explore the mechanism of NF-KappaB (NF-κB) interacting lncRNA (NKILA) in the pathological process of oral squamous cell carcinoma (OSCC). METHODS: NKILA expression in OSCC tissues, paracancerous tissues, and normal human oral keratinocytes and OSCC cell lines was detected using RT-qPCR. KB cells were selected for the follow-up experiments. The role of NKILA in cell proliferation, migration, invasion, and NF-κB signaling pathway was identified using the gain- and loss-of function of NKILA in OSCC cells. Additionally, the role of NKILA in vitro was determined by inducing xenograft tumors in nude mice. RESULTS: NKILA was poorly expressed in OSCC tissues and cells. Cell proliferation, invasion and migration, tumor volume and weight were significantly suppressed in cells with overexpressed NKILA, while silencing NKILA led to opposite trends. Moreover, the protein levels of p-IκBα and nuclear-p65 were markedly decreased, while the levels of IκBα and cytoplasm-p65 were enhanced in cells with overexpressed NKILA. CONCLUSION: This study provided evidence that NKILA could reduce proliferation, invasion and migration of OSCC cells through inhibiting the NF-κB signaling pathway. The findings may offer new insights for OSCC prevention and treatment.

Knockdown of circ_HIPK3 inhibits tumorigenesis of hepatocellular carcinoma via the miR-582-3p/DLX2 axis.

Hepatocellular carcinoma (HCC) is the most common type in the sub-classification of liver cancer. Circular RNAs (circRNAs) play a fundamental role in tumor occurrence and progression. This research aimed to investigate the role and molecular basis of circRNA homeodomain-interacting protein kinase 3 (circ_HIPK3) in HCC. Circ_HIPK3 and DLX2 levels were enhanced, and miR-582-3p level was reduced in HCC tissues and cells. Silencing of circ_HIPK3 impeded proliferation, migration and invasion and expedited apoptosis in HCC cells. Furthermore, circ_HIPK3 modulated HCC progression via sponging miR-582-3p, and miR-582-3p suppressed HCC progression via targeting DLX2. Moreover, circ_HIPK3 knockdown inhibited tumor growth in vivo. Circ_HIPK3 facilitated HCC progression by mediating miR-582-3p/DLX2 pathway, suggesting a new potential biomarker for HCC treatment.

Long non-coding RNA TUG1 promotes cell progression in hepatocellular carcinoma via regulating miR-216b-5p/DLX2 axis.

BACKGROUND: Accumulating evidence indicates that the long noncoding RNA taurine upregulated gene 1(TUG1) plays a critical role in cancer progression and metastasis. However, the overall biological role and clinical significance of TUG1 in hepatocellular carcinoma (HCC) remain largely unknown. METHODS: The expressions of TUG1, microRNA-216b-5p and distal-less homeobox 2 (DLX2) were detected by Quantitative real-time polymerase chain reaction (qRT-PCR). The target relationships were predicted by StarBase v.2.0 or TargetScan and confirmed by dual-luciferase reporter assay. The cell growth, apoptosis, migration and invasion were detected by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), Flow cytometry and Transwell assays, respectively. All protein expression levels were detected by western blot. Tumor xenografts were implemented to explore the role of TUG1 in vivo. RESULTS: We found that there was a marked rise in TUG1 expression in HCC tissues and cells, and knockdown of TUG1 repressed the growth and metastasis and promoted apoptosis of HCC cells. In particular, TUG1 could act as a ceRNA, effectively becoming a sink for miR-216b-5p to fortify the expression of DLX2. Additionally, repression of TUG1 impared the progression of HCC cells by inhibiting DLX2 expression via sponging miR-216b-5p in vitro. More importantly, TUG1 knockdown inhibited HCC tumor growth in vivo through upregulating miR-216b-5p via inactivation of the DLX2. CONCLUSION: TUG1 interacting with miR-216b-5p contributed to proliferation, metastasis, tumorigenesis and retarded apoptosis by activation of DLX2 in HCC.

Pholiotone A, a new polyketide derivative from Pholiota sp.

Pholiotone A (1), a new polyketide derivative, with tetrahydrobenzofuran-4(2H)-one skeleton, together with four known compounds, trichodermatides A (2) and B (3) and koninginins B (4) and E (5), were isolated from the crude extract of Pholiota sp. The structures of all the isolated compounds were determined mainly by NMR experiments, the modified Mosher method and electronic circular dichroism (ECD) calculations. The antifungal and cytotoxicity of all isolates were evaluated.

Expression profile analysis identifies IER3 to predict overall survival and promote lymph node metastasis in tongue cancer.

BACKGROUND: Lymph node metastasis is one of the most important factors affecting the prognosis of tongue cancer, and the molecular mechanism regulating lymph node metastasis of tongue cancer is poorly known. METHODS: The gene expression dataset GSE2280 and The Cancer Genome Atlas (TCGA) tongue cancer dataset were downloaded. R software was used to identify the differentially expressed hallmark gene sets and individual genes between metastatic lymph node tissues and primary tongue cancer tissues, and the Kaplan-Meier method was used to evaluate the association with overall survival. The screening and validation of functional genes was performed using western blot, q-PCR, CCK-8, migration and invasion assays, and lymphangiogenesis was examined by using a tube formation assay. RESULTS: Thirteen common hallmark gene sets were found based on Gene Set Variation Analysis (GSVA) and then subjected to differential gene expression analysis, by which 76 deregulated genes were found. Gene coexpression network analysis and survival analysis further confirmed that IER3 was the key gene associated with the prognosis and lymph node metastasis of tongue cancer patients. Knockdown of IER3 with siRNA inhibited the proliferation, colony formation, migration and invasion of Tca-8113 cells in vitro and it also inhibited the secretion and expression of VEGF-C in these cells. The culture supernatant of Tca-8113 cells could promote lymphangiogenesis and migration of lymphatic endothelial cells, and knockdown of IER3 in Tca-8113 cells suppressed these processes. CONCLUSION: Our study demonstrated that IER3 plays important roles in lymphangiogenesis regulation and prognosis in tongue cancer and might be a potential therapeutic target.

Metadherin enhances vulnerability of cancer cells to ferroptosis.

Ferroptosis is an iron-dependent, non-apoptotic form of regulated cell death driven by lipid hydroperoxides within biological membranes. Although therapy-resistant mesenchymal-high cancers are particularly vulnerable to ferroptosis inducers, especially phospholipid glutathione peroxidase 4 (GPx4) inhibitors, the underlying mechanism is yet to be deciphered. As such, the full application of GPx4 inhibitors in cancer therapy remains challenging. Here we demonstrate that metadherin (MTDH) confers a therapy-resistant mesenchymal-high cell state and enhanced sensitivity to inducers of ferroptosis. Mechanistically, MTDH inhibited GPx4, as well as the solute carrier family 3 member 2 (SLC3A2, a system Xc- heterodimerization partner), at both the messenger RNA and protein levels. Our metabolomic studies demonstrated that MTDH reduced intracellular cysteine, but increased glutamate levels, ultimately decreasing levels of glutathione and setting the stage for increased vulnerability to ferroptosis. Finally, we observed an enhanced antitumor effect when we combined various ferroptosis inducers both in vitro and in vivo; the level of MTDH correlated with the ferroptotic effect. We have demonstrated for the first time that MTDH enhances the vulnerability of cancer cells to ferroptosis and may serve as a therapeutic biomarker for future ferroptosis-centered cancer therapy.