TRIM Expression in HNSCC: Exploring the Link Between Ubiquitination, Immune Infiltration, and Signaling Pathways Through Bioinformatics.

Objective: Ubiquitination is an important post-translational modification. However, the significance of the TRIM family of E3 ubiquitin ligases in head and neck squamous cell carcinoma (HNSCC) has not been determined. In this study, the roles of TRIM E3 ubiquitin ligases in lymphovascular invasion in head and neck squamous cell carcinoma (HNSCC) were evaluated. Materials and Methods: TRIM expression and related parameters were obtained from UbiBrowser2.0, UALCAN, TIMER, TISIDB, LinkedOmics, STRING, and GeneMANIA databases. Immunohistochemistry was used to confirm their expression. Results: TRIM2, TRIM11, TRIM28, and TRIM56 were upregulated in HNSCC with lymphovascular invasion. TRIM expression was strongly associated with immune infiltration, including key treatment targets, like PD-1 and CTL4. Co-expressed genes and possible ubiquitination substrates included tumor-related factors. The TRIMs had predicted roles in ubiquitination-related pathways and vital signaling pathways, eg, MAPK, PI3K-Akt, and JAK-STAT signaling pathways. Conclusion: Ubiquitination mediated by four TRIMs might be involved in the regulation of tumor immunity, laying the foundation for future studies of the roles of the TRIM family on the prediction and personalized medicine in HNSCC. The four TRIMs might exert oncogenic effects by promoting lymphovascular invasion in HNSCC.

Development and Validation of a Novel Diagnostic Nomogram Model Using Serum Oxidative Stress Markers and AURKA for Prediction of Nasopharyngeal Carcinoma.

Purpose: The mortality rate of nasopharyngeal carcinoma (NPC) remains high due to the absence of quick and accurate diagnostic approaches at its early stage. Our aim is to evaluate the diagnostic value of the elevated expression of Aurora kinase A (AURKA) and the oxidative stress markers (such as glutathione, superoxide dismutase and malondialdehyde) in serum of NPC patients and to establish a nomogram model for predicting NPC on the ground of these biomarkers. Patients and Methods: Serum samples from 93 NPC patients and 94 healthy subjects were collected. Enzyme-linked immunosorbent assay (ELISA) was adopted to determine the AURKA level, while oxidative stress markers were measured by commercially available appropriate kits. Logistic regression was used for NPC predictor identification and nomogram construction. The training and validation cohorts (3:1) were randomly split up from the participants. Receiver operating characteristic (ROC) curves, calibration curves, and decision curve analyses (DCAs) were performed to validate the nomogram. Results: AURKA and malondialdehyde (MDA) levels were significantly high in the NPC population compared to the healthy controls (P < 0.0001). The nomogram resulted in an area under the curve (AUC) of 0.897 (95% confidence interval: 0.848-0.947) in the training set and AUC of 0.770 (0.628-0.912) in the validation set. The predicted probability and the actual probability matched well in the nomogram (P > 0.05). DCAs showed good results too. Conclusion: Serum levels of AURKA, SOD, and MDA have diagnostic values in NPC. The nomogram based on the identified biomarkers is favorable for NPC prediction.

Biosynthesis of Silver Nanoparticles Using the Biofilm Supernatant of Pseudomonas aeruginosa PA75 and Evaluation of Their Antibacterial, Antibiofilm, and Antitumor Activities.

Purpose: As an under-explored biomaterial, bacterial biofilms have a wide range of applications in the green synthesis of nanomaterials. The biofilm supernatant of Pseudomonas aeruginosa PA75 was used to synthesize novel silver nanoparticles (AgNPs). BF75-AgNPs were found to possess several biological properties. Methods: In this study, we biosynthesized BF75-AgNPs using biofilm supernatant as the reducing agent, stabilizer, and dispersant and investigated their biopotential in terms of antibacterial, antibiofilm, and antitumor activities. Results: The synthesized BF75-AgNPs demonstrated a typical face-centered cubic crystal structure; they were well dispersed; and they were spherical with a size of 13.899 ± 4.036 nm. The average zeta potential of the BF75-AgNPs was -31.0 ± 8.1 mV. The BF75-AgNPs exhibited strong antibacterial activities against the methicillin-resistant Staphylococcus aureus (MRSA), extended-spectrum beta-lactamase Escherichia coli (ESBL-EC), extensively drug-resistant Klebsiella pneumoniae (XDR-KP), and carbapenem-resistant Pseudomonas aeruginosa (CR-PA). Moreover, the BF75-AgNPs had a strong bactericidal effect on XDR-KP at 1/2 × MIC, and the expression level of reactive oxygen species (ROS) in bacteria was significantly increased. A synergistic effect was observed when the BF75-AgNPs and colistin were used for the co-treatment of two colistin-resistant XDR-KP strains, with fractional inhibitory concentration index (FICI) values of 0.281 and 0.187, respectively. Furthermore, the BF75-AgNPs demonstrated a strong biofilm inhibition activity and mature biofilm bactericidal activity against XDR-KP. The BF75-AgNPs also exhibited a strong antitumor activity against melanoma cells and low cytotoxicity against normal epidermal cells. In addition, the BF75-AgNPs increased the proportion of apoptotic cells in two melanoma cell lines, and the proportion of late apoptotic cells increased with BF75-AgNP concentration. Conclusion: This study suggests that BF75-AgNPs synthesized from biofilm supernatant have broad prospects for antibacterial, antibiofilm, and antitumor applications.

Efficacy of chemoradiotherapy in survival of stage â £ nasopharyngeal carcinoma and establishment of a prognostic model.

OBJECTIVES: The efficacy of chemoradiotherapy regimen in the treatment of stage Ⅳ nasopharyngeal carcinoma (Ⅳ NPC) is not clear. This retrospective study aimed to reveal the benefit of chemoradiotherapy in Ⅳ-NPC and to develop a survival prognostic model for the disease prediction. MATERIALS AND METHODS: The Surveillance, Epidemiology, and End Results (SEER) database at https://seer.cancer.gov was retrieved for stage Ⅳ NPC patients between 2004 and 2016. The patients were divided into two groups of radiotherapy and chemoradiotherapy according to the treatment method. Overall survival (OS) and cancer-specific survival (CSS) between the groups were compared using Kaplan-Meier analysis, log-rank test, and propensity matching score (PSM). Cox proportional hazards model, nomogram, and receiver operating characteristic (ROC) curve were employed to establish the prognostic model. RESULTS: A total of 729 patients with Ⅳ NPC were introduced, of whom 44 received radiotherapy and 685 received chemoradiotherapy. Results of statistical tests demonstrated that chemoradiotherapy was associated with improved OS and CSS, especially in the patients with ⅣA NPC (P < 0.05); further multivariate analysis with PSM confirmed that chemoradiotherapy benefited the patients' OS (HR: 0.24, 95% CI: 0.12-0.50; P < 0.001). Moreover, the efficacy of chemoradiotherapy was found significantly correlated to metastasis. Even though chemoradiotherapy had an obvious survival benefit in patients without metastasis, it only helped to improve the CSS in those with metastases. CONCLUSION: This study indicated that chemoradiotherapy could improve the survival of NPC patients at stage ⅣA and non-metastasis. The nomogram we established may provide reference for clinical treatment of NPC.

Elevated ACE Levels Indicate Diabetic Nephropathy Progression or Companied Retina Impaired.

Objectives: Renin-angiotensin-aldosterone system plays important roles in the development of diabetic nephropathy (DN), and angiotensin converting enzyme (ACE) is the key factor in the process from angiotensin I to angiotensin II, but the variation and roles of serum ACE in DN patients are still unclear. Methods: Forty-four type 2 diabetes mellitus (T2DM) patients, 75 DN patients, and 36 age-gender-matched healthy volunteers were recruited who attended Xiangya Hospital of Central South University in this case control study. Serum ACE levels and other indexes were tested with commercial kit. Results: ACE levels in DN were significantly higher than T2DM and controls (F = 9.66, P < 0.001). Serum ACE levels significantly correlated with UmALB (r = 0.3650, P < 0.001), BUN (r = 0.3102, P < 0.001), HbA1c (r = 0.2046, P = 0.0221), ACR (r = 0.4187, P < 0.001), ALB (r = -0.1885, P = 0.0192), and eGFR (r = -0.3955, P < 0.001), and we got an equation that Y = 2.839 + 0.648X1 + 2.001X2 + 0.003X3 - 6.637X4 +0.416X5 - 0.134X6 (Y: ACE; X1: BUN; X2: HbA1C; X3: UmALB; X4: gender; X5: ALB; X6: eGFR, R2 = 0.655). When DN patients were divided into advanced-stage and early-stage with or without DR, ACE levels would increase when early-stage DN develops into advanced-stage or companied with DR. Conclusion: Elevated serum ACE levels may hint DN progression or retina impaired of DN patients.

The Variation and Correlation of Serum Adiponectin, Nesfatin-1, IL-6, and TNF-α Levels in Prediabetes.

Background: The variation and correlation among adiponectin, nesfatin-1, tumor necrosis factor α (TNF-α), and interleukin 6 (IL-6), which may be involved in the development of the decline of health into prediabetes and diabetes, have not been elucidated. This study aims to investigate the roles of these cytokines in this process. Methods: Seventy-two type 2 diabetes mellitus (T2DM) patients, 75 prediabetics, and 72 healthy individuals were enrolled in our case control study. Serum adiponectin, nesfatin-1, TNF-α, and IL-6 were tested with appropriate kits, and primary data were analyzed with correct methods. Results: Serum levels of each cytokine in patients with prediabetes were between T2DM and the healthy, and significant differences were found among them. TNF-α and nesfatin-1 levels in T2DM were obviously different compared to prediabetes or the healthy; IL-6 and adiponectin levels in the healthy group were significantly changed in contrast to prediabetes or T2DM. Correlation analysis found that in prediabetics, adiponectin was positively correlated with TNF-α (R = 0.2939, P = 0.0105) and IL-6 (R = 0.3918, P = 0.0005), and their relationship was greatly strengthened in prediabetes accompanied by insulin resistance (TNF-α: R = 0.7732, P < 0.0001, IL-6: R = 0.6663, P = 0.0005). We also demonstrated that declined adiponectin (OR = 6.238, P = 0.019) and nesfatin-1 (OR = 2.812, P = 0.01) and elevated TNF-α (OR = 5.541, P = 0.001) were risk factors for prediabetes toward diabetes. Conclusions: This research proved significant variations of adiponectin, nesfatin-1, IL-6, and TNF-α levels in the healthy, prediabetics, and T2DM, suggesting a slow and gradual change during the progression from a healthy condition toward diabetes via prediabetes.

Influence of circulating nesfatin-1, GSH and SOD on insulin secretion in the development of T2DM.

Aims: To evaluate the correlation of nesfatin-1, GSH and SOD levels with ß-cell insulin secretion and their influence on insulin secretion in the development of type 2 diabetes mellitus (T2DM). Materials and methods: 75 patients with T2DM, 67 with prediabetes and 37 heathy participants were recruited in this study. Serum levels of nesfatin-1, GSH and SOD were quantified and statistically analyzed. Results: The levels of nesfatin-1, GSH and SOD in T2DM were significantly decreased (P < 0.001) compared to either in prediabetes or in healthy control, and significant reduction of these biomarkers was also observed in prediabetes when compared to the control (P < 0.001). Circulating nesfatin-1, GSH and SOD were not only strongly correlated with ß-cell insulin secretion, but also exerted remarkable influence on the secretion. Conclusion: Serum nesfatin-1, GSH and SOD are important factors involving insulin secretion in the development of T2DM, which may help provide new ideas for forthcoming investigations on the roles of these factors in pathogenesis of T2DM, as well as for active prediction and prevention of prediabetes before it develops into overt T2DM.

The role of Exosomes in the Pathogenesis of Nasopharyngeal Carcinoma and the involved Clinical Application.

Exosomes are nanoscale membrane vesicles, which carry biologically active substances of their cell of origin and play an important role in signal transduction and intercellular communication. At present, exosomes have been identified as a promising non-invasive liquid biopsy biomarker in the tissues and circulating blood of nasopharyngeal carcinoma (NPC) and found to participate in regulating pathophysiological process of the tumor. We here review recent insights gained into the molecular mechanisms of exosome-induced cell growth, angiogenesis, metastasis, immunosuppression, radiation resistance and chemotherapy resistance in the development and progression of NPC, as well as the clinical application of exosomes as diagnostic biomarkers and therapeutic agents. We also discuss the limitations and challenges in exosome application. We hope this review may provide some references for the use of exosomes in clinical intervention.

High preoperative albumin-bilirubin score predicts poor survival in patients with newly diagnosed high-grade gliomas.

OBJECTIVE: To determine the prognostic value of the preoperative Albumin-bilirubin (ALBI) score in high-grade glioma (HGG) patients. METHODS: A retrospective study of 194 HGG patients was conducted. ROC analysis was used to determine the optimal cut-off value of ALBI score. Univariate and multivariate analysis was performed to identify prognostic factors associated with progression free survival (PFS) and overall survival (OS). The resulting prognostic models were externally validated by a demographic-matched cohort of 130 HGG patients. RESULTS: Optimal cutoff value of ALBI score was -2.941. In training set, ALBI was correlated with age (P = 0.001), tumor location (P = 0.012) and adjuvant therapy (P = 0.016). Both PFS (8.27 vs. 18.40 months, P<0.001) and OS (13.93 vs. 27.57 months, P<0.001) were significantly worse in the ALBI-high group. Strikingly, patients in ALBI-low group had 56% decrease in the risk of tumor progression and 57% decrease in the risk of death relative to high ALBI. Multivariate analysis further identified ALBI score as an independent predictor for both PFS (HR=0.47, 95% CI 0.34, 0.66) and OS (HR=0.45, 95% CI 0.32, 0.63). The ALBI score remained independent prognostic value in the validation set for both PFS (P = 0.01) and OS (P = 0.007). Patients with low ALBI score had better PFS and OS in all subgroups by tumor grade and treatment modalities. CONCLUSIONS: The preoperative ALBI score is a noninvasive and valuable prognostic marker for HGG patients.