Pyroptosis patterns and immune infiltrates characterization in head and neck squamous cell carcinoma.

BACKGROUND: Pyroptosis plays an essential role in tumor immune responses and inflammation related to chemotherapy. Herein, we studied the characteristic patterns of pyroptosis in head and neck squamous cell carcinoma (HNSCC) to determine their prognostic and therapeutic effects. METHODS: Consensus clustering analysis was performed to classify patients into pyroptosis or gene clusters. A novel pyroptosis score was constructed by principal component analysis. Kaplan-Meier survival curves were used to show the prognostic value. We also assessed the functional enrichment, tumor mutation burden, immune cell infiltration, and the sensitivity to chemotherapy and immunotherapy between high and low pyroptosis score group. RESULTS: Two distinct pyroptosis clusters were defined based on the mRNA expression profiles of PRGs, which were related to immune activation in HNSCC. Notably, a pyroptosis score was constructed according to different expression gene signatures, and then, each HNSCC patient was classified into a low or high pyroptosis score group. Patients with low pyroptosis scores had better immunotherapeutic responses and higher sensitivities to chemotherapeutic agents (paclitaxel, docetaxel, and gemcitabine). Kaplan-Meier survival curves showed that the pyroptosis patterns were independent prognostic indicators regardless of the level of tumor mutation burden. CONCLUSIONS: Pyroptosis plays an essential role in immune infiltration in HNSCC. Quantifying the pyroptosis score of individual patients might suggest prognostic, immunotherapeutic, and chemotherapeutic strategies for HNSCC.

Comprehensive Analysis of NADH:Ubiquinone Oxidoreductase Subunit B3 in Gynecological Tumors and Identification of Its Natural Inhibitor Wedelolactone.

The aim of this study was to explore the role of NADH:ubiquinone oxidoreductase subunit B3 (NDUFB3) in human gynecological malignancies and to screen potential natural compounds targeting it. GEPIA and HPA databases were used to study the expression characteristics of NDUFB3. GO and KEGG enrichment analyses were performed using the R software clusterProfiler package. GSEA for NDUFB3 was performed using the LinkedOmics database. Natural compounds targeting NDUFB3 were screened by virtual screening and molecular docking. After NDUFB3 was depleted or wedelolactone treatment, cell proliferation was detected by CCK-8 assay. The production of reactive oxide species (ROS) in tumor cells was detected by dihydroethidium fluorescent probe. The cell cycle and apoptosis were evaluated by flow cytometry. It was revealed that NDUFB3 was highly expressed in ovarian cancer (OV), uterine corpus endometrial carcinoma (UCEC), and cervical squamous cell carcinoma (CESC). NDUFB3 expression was associated with multiple immunomodulators in CESC, OV, and UCEC. NDUFB3 was predicted to modulate MAPK signaling pathways in CESC, OV, and UCEC. Knocking down NDUFB3 inhibited the proliferation of CESC, OV, and UCEC cells, increased intracellular ROS production, and induced cell cycle arrest and apoptosis. Wedelolactone was a potential small molecule with a strong ability to bind with the active pocket of NDUFB3, and wedelolactone could kill CESC, OV, and UCEC cells partly via NDUFB3. In conclusion, NDUFB3 may be a potential biomarker and a new target for gynecological tumors, and wedelolactone may exert antitumor activity via targeting NDUFB3.

Effect of bariatric surgery on carotid intima-media thickness: A meta-analysis based on observational studies.

Objective: This meta-analysis aimed to investigate the effect of bariatric surgery on CIMT in people with obesity. Methods: PubMed, Web of Science, Embase, and the Cochrane Library were searched for observational studies assessing the effect of bariatric surgery on CIMT from inception to August 2022. Mean difference (MD) and 95% confidence intervals were calculated to assess CIMT. Results: A total of 23 studies, including 1,349 participants, were eligible to participate in this meta-analysis. The results revealed that CIMT was significantly decreased at 6 months, 12 months, and more than 18 months after bariatric surgery compared with baseline (6 months: MD = 0.09; P < 0.01; 12 months: MD = 0.12; P < 0.01; more than 18 months: MD = 0.14; P = 0.02). Meanwhile, laparoscopic Roux-en-Y gastric bypass (LRYGB) seemed to be more effective than laparoscopic sleeve gastrectomy (LSG) in lowering CIMT in terms of the type of surgery (LSG: MD = 0.11; P < 0.01; LRYGB: MD = 0.14; P < 0.01). Lastly, the benefits of bariatric surgery on CIMT was independent of gender (Male: MD = 0.06; P = 0.04; Female: MD = 0.08; P = 0.03). Conclusions: Bariatric surgery is consistently effective in reducing CIMT in people with obesity.

Immunologically modified enzyme-responsive micelles regulate the tumor microenvironment for cancer immunotherapy.

Immune checkpoint blockade has been proven to have great therapeutic potential and has revolutionized the treatment of tumors. However, various limitations remain, including the low response rate of exhausted T cells and mutual regulation of multiple immunosuppressive cell types that compromise the effect of single-target therapy. Nano-delivery systems can be used to regulate the tumor immune microenvironment in favor of immunotherapy. In this study, we constructed a polypeptide-based micellar system that encapsulates an aryl hydrocarbon receptor (AhR) inhibitor (CH223191) conjugated to T cell activator anti-CD28. The inhibition of AhR activation downregulates the fraction of immunosuppressive cells and effectively inhibits tumor cell metastasis. In addition, the combination with co-stimulatory antibodies improves T-cell activation and synergistically enhances the antitumor effect of AhR inhibitors. The micellar system developed in this study represents a novel and effective tumor immunotherapy approach.

A novel Pyroptosis-related long non-coding RNA signature for predicting the prognosis and immune landscape of head and neck squamous cell carcinoma.

BACKGROUND: Pyroptosis plays an essential function in carcinogenesis and the antitumor immune response. Herein, we constructed a pyroptosis-related long noncoding RNA (prLncRNA) signature to predict therapeutic effects and outcomes for head and neck squamous cell carcinoma (HNSCC) patients. METHODS: Patients obtained from the TCGA-HNSC project were divided randomly into the training as well as the validation sets at a ratio of 7:3. A novel prognostic prLncRNA signature was constructed from the results of the training set using the least absolute shrinkage and selection operation. The medium value was used as the basis for categorizing all HNSCC patients into a low- or high-risk cohort. Cox regression and Kaplan-Meier (KM) survival analyses were executed to estimate the prognostic value. We also evaluated the functional enrichment, tumor microenvironment, immune cell infiltration, and the sensitivity to chemotherapy and immunotherapy between the high- and low-risk cohorts. RESULTS: Nineteen prognostic prlncRNAs were identified to establish the prognostic signature. Multivariate Cox regression and KM survival analyses confirmed that this prlncRNA signature might serve as an independent prognostic indicator of patient survival, which was subsequently confirmed using a validating dataset. Multiple ROC curves indicated the prlncRNA signature presented a more predictive power than clinicopathological factors (age, sex, tumor grade, and tumor stage). GO, KEGG, and GSEA enrichment analysis disclosed several immune-related pathways which appeared to be enhanced in the low-risk cohort. ESTIMATE, CIBERSORT, and ssGSEA algorithms indicated considerable differences in the tumor microenvironment and immune cell infiltration in the low- and high-risk cohorts. Furthermore, the low-risk cohort was predicted to achieve a better response to immunotherapeutic drugs, while in contrast, the high-risk cohort would be more sensitive to chemotherapy drugs. CONCLUSIONS: Our findings robustly demonstrate that our constructed prlncRNA signature could serve as an efficient indicator of prognosis, immunotherapy response, and chemosensitivity for HNSCC patients.

Construction of a Ferroptosis-Related Gene Signature for Head and Neck Squamous Cell Carcinoma Prognosis Prediction.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is one of the most common malignant cancers, and few studies have demonstrated the value of ferroptosis-related genes in prognosis. METHODS: The original counts of RNA sequencing data and clinicopathological data were obtained from TCGA and GSE65858 datasets. Common ferroptosis-related genes related to prognosis were identified from the training set and were included in LASSO to determine the best prognosis. To evaluate the efficacy, time-dependent ROC and Kaplan-Meier (KM) survival analyses were applied. Moreover, univariate and multivariate Cox regression analyses were used to screen independent parameters of prognosis and build a nomogram. Eventually, possible biological pathways were proposed based on GSEA. RESULTS: Among 242 ferroptosis-related genes, we identified that the FLT3, IL6, Keap1, NQO1, SOCS1 and TRIB3 genes were significantly connected with HNSCC patient prognosis as a six-gene signature. After, the patients were divided into high- and low-risk groups based on the six-gene signature. The KM survival curves demonstrated that the high-risk group had worse OS (p < 0.0001) and higher AUC values (0.654, 0.735, and 0.679 for 1-, 3-, and 5-year survival, respectively) for the prognostic signature of the six genes compared with other genes, which were also validated in the GSE65858 dataset. Moreover, GSEA suggested that the epithelial mesenchymal transition pathway was abundant and that the mesenchymal status in the high-risk group was substantially higher than that in the low-risk group. Finally, the immune microenvironment and differences in the content of immune cell types were demonstrated. CONCLUSION: We established a six-ferroptosis-related-gene model crossing clinical prognostic parameters that can predict HNSCC patient prognosis and provide a reliable prognostic evaluation tool to assist clinical treatment decisions.

A novel pyroptosis-related gene signature to predict outcomes in laryngeal squamous cell carcinoma.

Pyroptosis, a pro-inflammatory form of programmed cell death, is associated with carcinogenesis and progression. However, there is little information concerning pyroptosis-related genes (PRGs) in laryngeal squamous cell carcinoma (LSCC). Herein, we aim to explore the prognostic value of PRGs in LSCC. The expression and clinical data of 47 PRGs in LSCC patients were obtained from The Cancer Genome Atlas. A novel prognostic PRG signature was constructed using least absolute shrinkage and selection operator analysis. Receiver operating characteristic (ROC) curves were drawn, and Kaplan-Meier survival Cox proportional hazard regression analyses were performed to measure the predictive capacity of the PRG signature. Furthermore, we constructed a six-PRG signature to divide LSCC patients into high- and low-risk groups. Patients in the high-risk group had worse overall survival than the low-risk group. The area under the time-dependent ROC curve was 0.696 for 1 year, 0.784 for 3 years, and 0.738 for 5 years. We proved that the PRGs signature was an independent predictor for LSCC. Functional enrichment analysis indicated that several immune-related pathways were significantly enriched in the low-risk group. Consistent with this, patients with low-risk scores had higher immune scores and better immunotherapeutic responses than the high-risk group. In conclusion, we established a novel PRGs signature that can predict outcome and response to immunotherapy of LSCC, pyroptosis may be a potential target for LSCC.

Vitamins and Helicobacter pylori: An Updated Comprehensive Meta-Analysis and Systematic Review.

BACKGROUND: Over recent decades, epidemiological studies have shown relationships between vitamins and Helicobacter pylori (H. pylori) infection and eradication, but the results are controversial. METHODS: A comprehensive meta-analysis and systematic review were conducted to clarify the relationships between common types of vitamins and H. pylori. We applied meta-regression, subgroup analysis and sensitivity analysis to obtain available evidence. Articles published from January 1991 to June 2021 in PubMed, EMBASE, and the Cochrane Library were searched. RESULTS: In total, we identified 48 studies. The results indicate that H. pylori -positive patients had lower serum vitamin B12 [standardized mean difference (SMD) = -0.30; 95% confidence interval (CI): -0.53 - -0.08], folate (SMD = -0.69; 95% CI: -1.34 - -0.04), vitamin C (SMD = -0.37; 95%CI: -0.57 - -0.18) and vitamin D (SMD = -0.34; 95% CI: -0.49 - -0.18) levels than H. pylori-negative patients. Patients in which H. pylori had been successfully eradicated had higher serum vitamin D levels (SMD = 1.37; 95% CI: 0.37-2.38) than in patients in which eradication had been unsuccessful. The serum vitamin B12 levels of H. pylori-positive patients improved after successful H. pylori eradication therapy (SMD = 1.85; 95% CI: 0.81-2.90), and antioxidant vitamin supplementation to an H. pylori eradication regimen improved the eradication rate (risk ratio = 1.22; 95% CI: 1.02-1.44 for per-protocol analysis; risk ratio = 1.25; 95% CI: 1.06-1.47 for intention-to-treat analysis). CONCLUSIONS: H. pylori infections decrease the serum levels of several types of vitamins, eradication of H. pylori could rescue its adverse effects, and antioxidant vitamin supplementation may improve the H. pylori eradication rate. SYSTEMATIC REVIEW REGISTRATION: identifier: CRD42021268127.

Epithelioid inflammatory myofibroblastic sarcoma of stomach: diagnostic pitfalls and clinical characteristics.

Inflammatory myofibroblastic tumor (IMT) is a neoplasm composed of spindled neoplastic myofibroblasts admixed with reactive lymphoplasmacytic cells, plasma cells, and/or eosinophils, which has an intermediate biological behavior. An IMT variant with plump round epithelioid or histiocytoid tumor cells, recognized as epithelioid inflammatory myofibroblastic sarcoma (EIMS), has a more clinically aggressive progression. To the best of our knowledge, only about 40 cases of EIMS have previously been reported in limited literature. Here, we report here a case of unusual EIMS with a relative indolent clinical behavior. We reviewed the literature for 18 similar cases. The patients present with a highly aggressive inflammatory myofibroblastic tumor characterized by round or epithelioid morphology, prominent neutrophilic infiltrate, and positive staining of ALK with RANBP2-ALK gene fusion or RANBP1-ALK gene fusion, or EML4-ALK gene fusion. Our case is the first case of primary stomach EIMS. Moreover, the mechanisms of the rare entity have not been widely recognized and require further study. Early accurate diagnosis and complete resection of this tumor is necessary. Some researchers suggest expression of PD-L1 may provide new strategies for ALK-targeted therapy.