JMJD6 functions as an oncogene and is associated with poor prognosis in esophageal squamous cell carcinoma.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is one of the most common malignant tumors with a high prevalence and poor prognosis. It is an urgent problem to deeply understand the molecular mechanism of ESCC and develop effective diagnostic and prognostic methods. METHODS: Using tumor tissue and corresponding paracancerous samples from 141 resected ESCC patients, we assessed Jumonji domain-containing protein 6 (JMJD6) expression using Immunohistochemical (IHC) staining. Kaplan-Meier survival analysis and univariate or multivariate analysis were used to investigate the relationship between JMJD6 expression and clinicopathological features. The expression status and prognostic value of JMJD6 were analyzed by bioinformatics and enrichment analysis. RESULTS: The expression of JMJD6 in ESCC samples was higher than that in the corresponding paracancerous samples, and high expression of JMJD6 was positively associated with poor prognosis of ESCC patients. In addition, bioinformatics analysis of the expression and prognosis of JMJD6 in a variety of tumors showed that high expression of JMJD6 was significantly associated with poor overall survival (OS) in ESCC patients. Enrichment analysis indicated that the high expression of genes similar to JMJD6, such as Conserved oligomeric Golgi 1(COG1), Major facilitator superfamily domain 11 (MFSD11) and Death Effector Domain Containing 2 (DEDD2), was associated with poor prognosis of ESCC, suggesting that JMJD6 might be involved in the occurrence and prognosis of ESCC. CONCLUSION: Our study found that JMJD6 expression was significantly increased in ESCC patients and positively correlated with prognosis, indicating that targeting JMJD6 might be an attractive prognostic biomarker and provides a potential treatment strategy for ESCC. TRIAL REGISTRATION: The study was approved by Tangdu Hospital ethics committee (No. TDLL-202110-02).

Ubiquitin-specific protease 28: the decipherment of its dual roles in cancer development.

As significant posttranslational modifications, ubiquitination and deubiquitination, whose balance is modulated by ubiquitin-conjugating enzymes and deubiquitinating enzymes (DUBs), can regulate many biological processes, such as controlling cell cycle progression, signal transduction and transcriptional regulation. Belonging to DUBs, ubiquitin-specific protease 28 (USP28) plays an essential role in turning over ubiquitination and then contributing to the stabilization of quantities of substrates, including several cancer-related proteins. In previous studies, USP28 has been demonstrated to participate in the progression of various cancers. Nevertheless, several reports have recently shown that in addition to promoting cancers, USP28 can also play an oncostatic role in some cancers. In this review, we summarize the correlation between USP28 and tumor behaviors. We initially give a brief introduction of the structure and related biological functions of USP28, and we then introduce some concrete substrates of USP28 and the underlying molecular mechanisms. In addition, the regulation of the actions and expression of USP28 is also discussed. Moreover, we concentrate on the impacts of USP28 on diverse hallmarks of cancer and discuss whether USP28 can accelerate or inhibit tumor progression. Furthermore, clinical relevance, including impacting clinical prognosis, influencing therapy resistance and being the therapy target in some cancers, is depicted systematically. Thus, assistance may be given to future experimental designs by the information provided here, and the potential of targeting USP28 for cancer therapy is emphasized.

Transcription factor ZEB1 regulates PLK1-mediated SKA3 phosphorylation to promote lung cancer cell proliferation, migration and cell cycle.

Lung cancer (LC) is one of the most common malignancies worldwide with low 5-year survival rate. The mechanism of spindle and kinetochore-associated complex subunit 3 (SKA3) in LC tumorgenesis remains largely unclear. The expression of SKA3 in LC cells was detected by quantitative PCR. Cell proliferation, migration and cell cycle were evaluated by functional assays including 5-ethynyl-2'-deoxyuridine, wound healing, transwell assays and flow cytometry analysis. Bioinformatics analysis, chromatin immunoprecipitation, luciferase reporter, co-immunoprecipitation and in vitro phosphorylation assays were applied to explore the interactions between zinc finger E-box binding homeobox 1 (ZEB1) and SKA3/polo-like kinase 1 (PLK1). SKA3 is highly expressed in LC cell lines and drives LC cell proliferation, migration and cell cycle. PLK1 also enhances the malignancy of LC cells. PLK1 can mediate SKA3 phosphorylation and enhance the stability of SKA3 protein, thus promoting LC progression. Besides, we found that transcription factor ZEB1 transcriptionally activates SKA3/PLK1 expression, contributing to LC cell malignancy. This study demonstrated that transcription factor ZEB1 modulates PLK1-mediated SKA3 phosphorylation to accelerate LC cell growth, migration and cycle, which might offer novel insight into LC treatment.

Laparoscopic gastric dissociation using a two-port approach in minimally invasive esophagectomy.

BACKGROUND: A new approach for laparoscopic gastric dissociation in minimally invasive esophagectomy (MIE) was attempted. This study aimed to evaluate the short-term outcomes, safety, and efficacy of two-port laparoscopy using the McKeown procedure. METHODS: This retrospective study included 206 consecutive patients with esophageal cancer who underwent a modified two-port laparoscopic or the traditional five-port McKeown procedure at our institution from August 2019 to August 2021. Surgical outcomes of the two methods were compared. RESULTS: Of the 206 patients, 106 (51.46%) underwent the modified two-port procedure, whereas 100 (48.54%) underwent the traditional five-port procedure. Subsequently, 182 propensity score-matched patients were compared. No significant differences were observed in laparoscopic operative time, blood loss during laparoscopic surgery, number of dissected lymph nodes, and pain score on postoperative day 1 between the two groups. The rate of complication and postoperative length of hospital stay did not differ significantly between the two groups. The total hospitalization cost also did not differ significantly between the two groups (p = 0.325). No postoperative deaths occurred in either group. CONCLUSIONS: Our findings demonstrate that laparoscopic gastric dissociation using the two-port approach in MIE is a safe and effective procedure, with short-term outcomes comparable to those of the traditional five-port procedure in patients with esophageal cancer. Larger studies with longer follow-up duration are warranted.

Clinicopathological characteristics and prognostic significance of HDAC11 protein expression in non-small cell lung cancer: a retrospective study.

Background: Although the prognosis of non-small cell lung cancer (NSCLC) can be assessed based on pathological type, disease stage and inflammatory indicators, the prognostic scoring model of NSCLC still needs to improve. HDAC11 is associated with poor prognosis of partial tumors, but its prognostic relationship with NSCLC is poorly understood. In this study, the role of HDAC11 in NSCLC was studied to evaluate relationship with disease prognosis and potential therapeutic target. Methods: The clinicopathological and paracancerous tissues of patients with NSCLC primarily diagnosed in Tangdu Hospital from 2009 to 2013 were collected. Follow-up of patients were made every three months and the last follow-up period was December 2018. The expression of HDAC11 was assessed by immunohistochemistry (IHC). Then, weighted gene co-expression network analysis (WGCNA) was used to analyze the relationship between HDAC11 expression and the prognosis of lung adenocarcinoma (LUAD) patients. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Kaplan-Meier plotter database was used to verify the connection between hub genes and tumor stage and prognosis. We accessed the relationship between HDAC11 expression and clinicopathological features, and impact on the prognosis. Results: The study assessed 326 patients with NSCLC. Compared with adjacent tissues, HDAC11 expression was upregulated (HR =1.503, 95% CI: 1.172 to 1.927, P=0.001). Kaplan-Meier survival analyses showed that HDAC11 expression was closely related to OS of NSCLC patients (P=0.0011). Univariate and multivariate analyses showed that the independent risk factors of OS were clinical stage, HDAC11 expression, and HDAC11 differentiation (all P≤0.001). HDAC11 was significantly associated with prognosis in LUAD. A total of 1,174 differential genes and WGCNA were obtained to construct a co-expression network in LUAD. The GO and KEGG pathway enrichment analyses showed the relevance with staphylococcus aureus infection, NOD-like receptor signaling pathway, and others. The results of LUAD survival analysis showed that HDAC11-related genes NKX2-5 and FABP7 were significantly associated with LUAD prognosis. Conclusions: The high expression of HDAC11 is related to the poor prognosis of LUAD, and it is expected to become a therapeutic target and prognostic evaluation therapy for LUAD in the future. However, the relevant results need to be further studied and verified.

Influenza a virus triggers acute exacerbation of chronic obstructive pulmonary disease by increasing proinflammatory cytokines secretion via NLRP3 inflammasome activation.

BACKGROUND: Influenza A virus (IAV) triggers acute exacerbation of chronic obstructive pulmonary disease (AECOPD), but the molecular mechanisms remain unclear. In this study, we investigated the role of IAV induced NLRP3 inflammasome activation to increase airway inflammation response in the progression of AECOPD. METHODS: Human bronchial epithelial cells were isolated and cultured from normal and COPD bronchial tissues and co-cultured with IAV. The NLRP3 inflammasome associated genes were identified using RNA sequencing, and the expressions of NLRP3 inflammasome components were measured using qRT-PCR and western blot after cells were transfected with siRNA and treated with MCC950. Moreover, IAV-induced COPD rat models were established to confirm the results; 37 AECOPD patients were included to measure the serum and bronchoalveolar lavage fluid (BALF) of interleukin (IL)-18 and IL-1ß. RESULTS: Increased levels of NLRP3 inflammasome components were not seen until 6 h post-inoculation in normal cells. However, both cell groups reached peak NLRP3 level at 12 h post-inoculation and maintained it for up to 24 h. ASC, Caspase-1, IL-1ß and IL-18 were also elevated in a similar time-dependent pattern in both cell groups. The mRNA and protein expression of the NLRP3 inflammasome components were decreased when COPD cells treated with siRNA and MCC950. In COPD rats, the NLRP3 inflammasome components were elevated by IAV. MCC950 alleviated lung damage, improved survival time, and reduced NLRP3 inflammasome components expression in COPD rats. Additionally, the serum and BALF levels of IL-1ß and IL-18 were increased in AECOPD patients. CONCLUSIONS: NLRP3 inflammasome is activated in COPD patients as a pre-existing condition that is further exacerbated by IAV infection.

Lysine Acetylation/Deacetylation Modification of Immune-Related Molecules in Cancer Immunotherapy.

As major post-translational modifications (PTMs), acetylation and deacetylation are significant factors in signal transmission and cellular metabolism, and are modulated by a dynamic process via two pivotal categories of enzymes, histone acetyltransferases (HATs) and histone deacetylases (HDACs). In previous studies, dysregulation of lysine acetylation and deacetylation has been reported to be associated with the genesis and development of malignancy. Scientists have recently explored acetylation/deacetylation patterns and prospective cancer therapy techniques, and the FDA has approved four HDAC inhibitors (HDACi) to be used in clinical treatment. In the present review, the most recent developments in the area of lysine acetylation/deacetylation alteration in cancer immunotherapy were investigated. Firstly, a brief explanation of the acetylation/deacetylation process and relevant indispensable enzymes that participate therein is provided. Subsequently, a multitude of specific immune-related molecules involved in the lysine acetylation/deacetylation process are listed in the context of cancer, in addition to several therapeutic strategies associated with lysine acetylation/deacetylation modification in cancer immunotherapy. Finally, a number of prospective research fields related to cancer immunotherapy concepts are offered with detailed analysis. Overall, the present review may provide a reference for researchers in the relevant field of study, with the aim of being instructive and meaningful to further research as well as the selection of potential targets and effective measures for future cancer immunotherapy strategies.

Microstructure and Superior Corrosion Resistance of an In-Situ Synthesized NiTi-Based Intermetallic Coating via Laser Melting Deposition.

A nickel-titanium (NiTi)-based intermetallic coating was in-situ synthesized on a Ti-6Al-4V (TC4) substrate via laser melting deposition (LMD) using Ni-20Cr and TC4 powders. Scanning electron microscopy, X-ray diffraction, a digital microhardness tester and an electrochemical analyzer were used to evaluate the microstructure, Vicker's microhardness and electrochemical corrosion resistance of the intermetallic coating. Results indicate that the microstructure of the intermetallic coating is composed of NiTi2, NiTi and Ni3Ti. The measured microhardness achieved is as high as ~850 HV0.2, ~2.5 times larger than that of the TC4 alloy, which can be attributed to the solid solution strengthening of Al and Cr, dispersion strengthening of the intermetallic compounds, and grain refinement strengthening from the rapid cooling of LMD. During the electrochemical corrosion of 3.5% NaCl solution, a large amount of Ti ions were released from the intermetallic coating surface and reacted with Cl- ions to form [TiCl6]2 with an increase in corrosion voltage. In further hydrolysis reactions, TiO2 formation occurred when the ratio of [TiCl6]2- reached a critical value. The in-situ synthesized intermetallic coating can achieve a superior corrosion resistance compared to that of the TC4 alloy.

Major complications of minimally invasive Ivor Lewis oesophagectomy using the purse string-stapled anastomotic technique in 215 patients with oesophageal carcinoma.

OBJECTIVES: The purse string-stapled anastomotic technique is a method for minimally invasive oesophagectomy with intrathoracic anastomosis, in which a purse string is hand sewn without the necessity of specialized devices, such as OrVil and Endo-Stitch. Since this technique was first reported by our surgical team in 2012, several measures in the operation have been refined. Furthermore, there are very few literature reports on the major complications of minimally invasive oesophagectomy with this technique. This article studies the major complications of minimally invasive Ivor Lewis oesophagectomy with this technique and explores methods for prevention and treatment. METHODS: Clinical data of 215 patients with oesophageal cancer who underwent thoracoscopic laparoscopic oesophagectomy with intrathoracic anastomosis from October 2011 to December 2015 were analysed. No patients received preoperative radiotherapy and chemotherapy. During the operation, the purse string was simply hand sewn before it was tightened and tied, and anastomosis was performed using a circular stapler. RESULTS: Six (2.79%) patients developed anastomotic leakage, and all of them were treated conservatively. Three (1.40%) patients experienced postoperative haemorrhage; of them, 2 were cured with conservative treatment. The remaining patient was cured by endoscopic management using titanium clips. Thirty-nine (18.14%) patients experienced postoperative pulmonary complications. One (1.47%) patient died due to pulmonary infection with respiratory failure although he had received mechanical ventilator support after tracheotomy. Five (2.33%) patients developed chyle leakage and 5 (2.33%) patients developed recurrent laryngeal nerve injuries. CONCLUSIONS: The incidence of major complications is acceptable for thoracoscopic laparoscopic oesophagectomy with intrathoracic anastomosis using this purse string-stapled anastomotic technique, which is feasible and safe to perform. Some measures designed in the operation will be conducive to reduce the incidence of major complications.