Three species of rape responded to cadmium and melatonin alleviating Cd-toxicity in species-specific strategy.

Cadmium (Cd) pollution has been a significant concern in heavy metal pollution, prompting plants to adopt various strategies to mitigate its damage. While the response of plants to Cd stress and the impact of exogenous melatonin has received considerable attention, there has been limited focus on the responses of closely related species to these factors. Consequently, our investigation aimed to explore the response of three different species of rape to Cd stress and examine the influence of exogenous melatonin in this scenario. The research findings revealed distinctive responses among the investigated rape species. B. campestris showed the resistance to Cd and exhibited lower Cd absorption and sustained its physiological activity under Cd stress. In contrast, B. juncea accumulated much Cd and increased the amount of anthocyanin to mitigate the Cd-damage. Furthermore, B. napus showed the tolerance to Cd and tended to accumulate Cd in vacuoles under Cd stress, thereby decreasing the Cd damage and leading to higher activity of antioxidant enzymes and photosynthesis. Moreover, the application of exogenous melatonin significantly elevated the melatonin level in plants and mitigated Cd toxicity by promoting the activity of antioxidant enzymes, reducing Cd absorption, enhancing the chelating capacity with Cd, decreasing Cd accumulation in organelles, and reducing its fluidity. Specifically, exogenous melatonin increased the FHAc content in B. campestris, elevated the phytochelatins (PCs) level in B. napus, and stimulated photosynthesis in B. juncea. In summary, the findings underscore the species-specific responses of the three species of rape to both Cd stress and exogenous melatonin, highlighting the potential for tailored mitigation strategies based on the unique characteristics of each species.

Bioprospecting of Actinobacterial Diversity and Antibacterial Secondary Metabolites from the Sediments of Four Saline Lakes on the Northern Tibetan Plateau.

The Tibetan Plateau, known as the "Roof of the World" and "The Third Pole", harbors numerous saline lakes primarily distributed in the Northern Tibetan Plateau. However, the challenging conditions of high altitude, low oxygen level, and harsh climate have limited investigations into the actinobacteria from these saline lakes. This study focuses on investigating the biodiversity and bioactive secondary metabolites of cultivable actinobacteria isolated from the sediments of four saline lakes on the Northern Tibetan Plateau. A total of 255 actinobacterial strains affiliated with 21 genera in 12 families of 7 orders were recovered by using the pure culture technique and 16S rRNA gene phylogenetic analysis. To facilitate a high-throughput bioactivity evaluation, 192 isolates underwent OSMAC cultivation in a miniaturized 24-well microbioreactor system (MATRIX cultivation). The antibacterial activity of crude extracts was then evaluated in a 96-well plate antibacterial assay. Forty-six strains demonstrated antagonistic effects against at least one tested pathogen, and their underlying antibacterial mechanisms were further investigated through a dual-fluorescent reporter assay (pDualrep2). Two Streptomyces strains (378 and 549) that produce compounds triggering DNA damage were prioritized for subsequent chemical investigations. Metabolomics profiling involving HPLC-UV/vis, UPLC-QTOF-MS/MS, and molecular networking identified three types of bioactive metabolites belonging to the aromatic polyketide family, i.e., cosmomycin, kidamycin, and hedamycin. In-depth analysis of the metabolomic data unveiled some potentially novel anthracycline compounds. A genome mining study based on the whole-genome sequences of strains 378 and 549 identified gene clusters potentially responsible for cosmomycin and kidamycin biosynthesis. This work highlights the effectiveness of combining metabolomic and genomic approaches to rapidly identify bioactive chemicals within microbial extracts. The saline lakes on the Northern Tibetan Plateau present prospective sources for discovering novel actinobacteria and biologically active compounds.

Georgenia halotolerans sp. nov., a halotolerant actinobacterium isolated from Taklamakan desert soil.

A Gram-stain-positive, aerobic, non-motile, non-spore-forming and rod-shaped actinobacterium, designated strain 10Sc9-8T, was isolated from Taklamakan desert soil sampled in the Xinjiang Uygur Autonomous Region, China. Strain 10Sc9-8T grew at 8‒37 °C (optimum, 28‒30 °C), pH 6.0‒10.0 (optimum, pH 7.0-8.0) and in the presence of 0‒15 % (w/v) NaCl (optimum, 0-3 %). Phylogenetic analysis based on 16S rRNA gene sequence suggested that strain 10Sc9-8T was affiliated with members of the genus Georgenia and showed the highest 16S rRNA gene sequence similarity to Georgenia yuyongxinii Z443T (97.4 %). Phylogenomic analysis based on the whole genome sequences indicated that strain 10Sc9-8T should be assigned into the genus Georgenia. The average nucleotide identity and digital DNA-DNA hybridization values calculated from the whole genome sequences indicated that strain 10Sc9-8T was clearly separated from other closely related species of the genus Georgenia with values below the thresholds for species delineation. Chemotaxonomic analyses showed that the cell-wall peptidoglycan was in a variant of A4α type with an interpeptide bridge comprising l-Lys-l-Ala-Gly-l-Asp. The predominant menaquinone was MK-8(H4). The polar lipids comprised diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol, phosphatidylinositol mannoside, several unidentified phospholipids, glycolipids and one unidentified lipid. The major fatty acids were anteiso-C15 : 0, anteiso-C15 : 1 A and C16 : 0. The genomic DNA G+C content was 72.7 mol%. On the basis of phenotypic, phylogenetic and phylogenomic data, strain 10Sc9-8T represents a novel species of the genus Georgenia, for which the name Georgenia halotolerans sp. nov. is proposed. The type strain is 10Sc9-8T (=JCM 33946T=CPCC 206219T).

The Diagnosis and Management of Advanced Endolymphatic Sac Tumor.

Endolymphatic sac tumor (ELST) is a group of low-grade malignant tumors originating from the endolymphatic sac of the inner ear. It is rare in the clinic and has the biological characteristics of slow growth and local aggression. Due to the lack of specificity in the clinical manifestations of patients with ELST, many cases have entered the advanced stage at the time of diagnosis. However, there are still great challenges in the treatment of advanced ELSTs. Here, the authors describe a case of advanced ELST, which relapsed after 2 operations. This time, the authors chose the transotic approach for tumor resection, which achieved the goal of complete resection of the tumor, and the patient recovered smoothly after surgery. There were no surgical complications and no tumor recurrence after the follow-up. Through literature review and our own experience, the authors suggest that complete surgical resection is the first choice for both primary and recurrent advanced ELSTs. The choice of a reasonable surgical approach is the key to ensuring complete resection of the tumor, while preoperative angiography and embolization, fine treatment of important structures during surgery, and postoperative long-term follow-up are equally important for patients with advanced ELST to obtain a good prognosis.

Circ_0000052/miR-382-3p axis induces PD-L1 expression and regulates cell proliferation and immune evasion in head and neck squamous cell carcinoma.

A better understanding of the mechanisms underlying PD-L1 aberrant expression in head and neck squamous cell carcinoma (HNSCC) will help reveal predictive biomarkers and overcome resistance to treatment. In this study, the prognostic significance of PD-L1 in forty-five HNSCC archival samples was determined by qRT-PCR. The biological function associated with malignant behaviour was assessed by PD-L1 depletion, miR-382-3p re-expression and regulation of circ_0000052. The interactions of PD-L1-miRNA and miRNA-circRNA were determined by qRT-PCR, Western blot analysis, dual-luciferase reporter assays and RNA immunoprecipitation assays. PD-L1 was highly expressed in patient samples and cancer cell lines. Higher levels of PD-L1 were associated with patient recurrences and play a pivotal role in regulating cell proliferation, migration, invasion, clonogenicity and apoptosis. In addition to demonstrating that the IFN-γ/JAK2/STAT1 signalling pathway can induce PD-L1 overexpression in HNSCC, a novel mechanism by which upregulated circ_0000052 mediates PD-L1 overexpression was also demonstrated. To do this, circ_0000052 competitively binds to miR-382-3p and alleviates its repression of PD-L1. This leads to overexpression of PD-L1, causing the aggressiveness of the cells. Our data demonstrate that circ_0000052 is oncogenic, and the circ_0000052/miR-382-3p/PD-L1 axis is critical in HNSCC progression. The manipulation of circRNAs/miRNAs in combination with anti-PD-L1 therapy may improve personalized disease management.

Total Resection of Cerebellopontine Angle Meningioma via Presigmoid Transmastoid Approach: An Otologist's Perspective.

PURPOSE: Cerebellopontine angle meningiomas (CPAMs) are benign tumors that arise from the dura mater of the petrosal surface of the temporal bone, lateral to the trigeminal nerve. This study aimed to describe 1 case of CPAMs violating the mastoid and highlight the unique superiority of the presigmoid transmastoid approach for this type of CPAMs from an otologist's perspective. METHODS: One case of specific CPAMs treated by total resection via presigmoid transmastoid approach in otomicrosurgery was described. RESULTS: A patient was referred for the left intracranial space-occupying lesion found in physical examination. Surgical resection via presigmoid transmastoid approach was performed and there was no sign of recurrence of tumor 2 years after the operation. CONCLUSIONS: Presigmoid transmastoid approach in otomicrosurgery is suitable for CPAMs invading the mastoid. It is suggested that neurosurgeons and ear surgeons should comprehensively analyze the type and extent of the tumor and flexibly adopt surgical methods to ensure it is the best for patients.

Erratum: Overexpression of lncRNA H19/miR-675 promotes tumorigenesis in head and neck squamous cell carcinoma: Erratum.

[This corrects the article DOI: 10.7150/ijms.16571.].

Mechanism of Action of Flavonoids of Oxytropis falcata on the Alleviation of Myocardial Ischemia-Reperfusion Injury.

Oxytropis falcata Bunge is a plant used in traditional Tibetan medicine, with reported anti-inflammatory and antioxidants effects and alleviation of myocardial ischemia reperfusion injury (MIRI). However, the underlying mechanism against MIRI and the phytochemical composition of O. falcata are vague. One fraction named OFF1 with anti-MIRI activity was obtained from O. falcata, and the chemical constituents were identified by ultra-high-performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS). The potential targets and signaling pathways involved in the action of O. falcata against MIRI were predicted by network pharmacology analysis, and its molecular mechanism on MIRI was determined by in vitro assays. The results revealed that flavonoids are the dominant constituents of OFF1. A total of 92 flavonoids reported in O. falcata targeted 213 potential MIRI-associated factors, including tumor necrosis factor (TNF), prostaglandin-endoperoxide synthase 2 (PTGS2), and the NF-κB signaling pathway. The in vitro assay on H9c2 cardiomyocytes subjected to hypoxia/reoxygenation injury confirmed that the flavonoids in OFF1 reduced myocardial marker levels, apoptotic rate, and the inflammatory response triggered by oxidative stress. Moreover, OFF1 attenuated MIRI by downregulating the ROS-mediated JNK/p38MAPK/NF-κB pathway. Collectively, these findings provide novel insights into the molecular mechanism of O. falcata in alleviating MIRI, being a potential therapeutic candidate.

Expression of PD-L1 and CD4+ tumor-infiltrating lymphocytes predict survival in head and neck squamous cell carcinoma.

The clinical efficacy of immune checkpoint blockade has been recently demonstrated in a variety of cancer types. The aim of the present study was to characterize the expression profile of tumor-infiltrating lymphocytes (TILs) and programmed death-ligand 1 (PD-L1) in head and neck squamous carcinoma (HNSCC). A total of 63 patients with HNSCC were enrolled in the present study. CD3+ and CD4+ TILs and the expression of PD-L1 were detected by immunohistochemistry. PD-L1 mRNA levels were evaluated by reverse transcription-quantitative PCR analysis. The association of TILs and PD-L1 with patient clinicopathological characteristics was also assessed. CD3+ and CD4+ TILs were detected in 100% of the samples. CD3+ was the predominant subset of TILs. PD-L1 was expressed in 53 of 61 (86%) patients when a score of ≥1 on tumor cells was considered positive and in 28 patients (45.2%) when a score of >5 on tumor cells was considered positive. PD-L1 mRNA levels were determined to be significantly correlated with PD-L1 protein expression. Survival analysis demonstrated that high CD4+ TILs were associated with improved overall survival (OS) and disease-free survival (DFS), and furthermore, the association of high PD-L1 expression with unfavorable OS and DFS was statistically significant. Multivariate analysis identified CD4+ TILs and PD-L1 as prognostic markers for HNSCC. The results of the present study suggested that increased CD4+ TILs in HNSCC may be associated with improved outcomes, while high expression of PD-L1 may indicate unfavorable OS and DFS; thus, these factors may serve as predictors of the response to immune checkpoint therapy.

A Case of Atypical Skull Base Osteomyelitis Secondary to Otitis Media Due to Delayed Diagnosis.

ABSTRACT: Skull base osteomyelitis that is secondary to otitis media is extremely rare in the modern antibiotic era. The authors present an 84-year-old male with atypical skull base osteomyelitis that developed from otitis media during the COVID-19 pandemic due to delayed diagnosis and partial treatment which is blamed for development of skull base osteomyelitis. The atypical presentations of skull base osteomyelitis pose a diagnostic challenge. This case highlights that even otitis media is a potentially fatal infection in older patients with diabetes. Early diagnosis and aggressive management of skull base osteomyelitis are of upmost importance and will ensure a more favorable prognosis.

MiR-543/Numb promotes proliferation, metastasis, and stem-like cell traits of prostate cancer cells.

MiR-543 and Numb are associated with various malignancies, including prostate cancer (PCa). However, whether miR-543 regulates Numb in PCa development remains unclear. In this study, we identified Numb as a direct target of miR-543. The role of miR-543 was examined both in vitro and in vivo. The in vivo effects of miR-543 were investigated using tumor transplantation experiments and a lung metastasis model. The in vitro effects of miR-543 on proliferation, migration, invasion, and cancer stem-like cell (CSC)-associated properties were also examined. The binding sites of Numb were predicted using bioinformatics tools and confirmed by luciferase and rescue assays. QRT-PCR and western blot analyses were used to detect target expression levels. Expression levels of both miR-543 and Numb were manipulated in CD44+ and CD44-PCa cells followed by a series of functional assays. The results demonstrated that miR-543 promoted PCa growth and metastasis both in vivo and in vitro. Luciferase reporter assays, qRT-PCR, and western blot analyses revealed Numb as a direct target of miR-543. The function of miR-543 was abolished by Numb, as shown in rescue experiments. Moreover, miR-543 was verified to promote CSC properties, whereas Numb elicited the opposite effects. MiR-543 also influenced the expression of several stem-like factors, including Dll4, NF-κB, c-myc, and Oct-4, and the Numb/p53 signaling pathway. Taken together, these results demonstrate that miR-543 plays an oncogenic role by negatively controlling Numb, revealing the existence of an miR-543/Numb/p53 regulatory pathway in PCa tumorigenesis and development.

Long non-coding RNA ANRIL promotes proliferation, clonogenicity, invasion and migration of laryngeal squamous cell carcinoma by regulating miR-181a/Snai2 axis.

BACKGROUND: Laryngeal squamous cell carcinoma (LSCC) is the common cancer with poor prognosis. Long non-coding RNA (lncRNA) ANRIL has been proven to play an important role in many cancers. However up to now, the role of ANRIL in LSCC is still poorly understood. The present study aimed to investigate the role and underlying mechanisms of ANRIL and miR-181a in LSCC. METHODS: Expression of ANRIL, miR-181a and Snai2 in both LSCC tissues and cells was determined by qRT-PCR. CCK-8 assay, colony formation assay, flow cytometry analysis and transwell assay were conducted to detect cell proliferation, clonogenicity, apoptosis, invasion and migration, respectively. The binding between ANRIL and miR-181a, as well miR-181a and Snai2 was confirmed by dual luciferase reporter assay. Western blotting was used to determine the protein levels of Snail, Slug, E-cadherin, N-cadherin and Vimentin. RESULTS: ANRIL was up-regulated while miR-181a was down-regulated in LSCC tissues. ANRIL was negatively correlated with miR-181a and was positively correlated with Snai1 and Snai2. Dual luciferase reporter assay showed ANRIL could directly sponge miR-181a to counteract its suppression on Snai2, serving as a positive regulator of Snai2. Either knockdown of ANRIL or overexpression of miR-181a significantly inhibited the proliferation, clonogenicity, invasion, migration and epithelial mesenchymal transformation (EMT), as well as promoted the apoptosis of LSCC cells, and knockdown of miR-181a reversed the effects. CONCLUSION: Inhibition of ANRIL could suppress cell proliferation, clonogenicity, invasion and migration, as well as enhance cell apoptosis of LSCC cells through regulation of miR-181a/Snai2 axis, indicating that ANRIL might be a promising therapeutic target during the treatment of LSCC.

Overexpression of lncRNA H19/miR-675 promotes tumorigenesis in head and neck squamous cell carcinoma.

There is accumulating evidence indicating that long non-coding RNA H19 and its mature product miR-675 play essential roles for tumor growth and progression. However, their prognostic value in human head and neck squamous cell carcinoma (HNSCC), particular in laryngeal carcinoma, remains to be elucidated. In this study, we observed that both H19 and miR-675 were significantly overexpressed in a cohort of 65 primary tumor samples and two HNSCC cell lines. Importantly, when paired with patient follow-up data, higher expression of either H19 or miR-675 was significantly correlated with higher risk of patient relapse, and associated with worse overall survival and poor disease-free survival. Knockdown miR-675 caused significant reduction of cell viability, migratory and invasive capabilities. Taken together, these results suggest that the strong correlation of H19 overexpression together with higher miR-675 and lymph node metastases could be useful predictive markers, indicating a potentially therapeutic strategy for HNSCC patients.

Clinical evaluation of balloon dilation eustachian tuboplasty surgery in adult otitis media with effusion.

CONCLUSION: BDET might be effective for the patients with OME, and proved to be an efficacious and mini-invasive treatment for OME. OBJECTIVES: To evaluate the therapeutic benefits of balloon dilation eustachian tuboplasty (BDET) in the treatment of adult patients with otitis media with effusion (OME) caused by eustachian tube dysfunction (ETD). METHODS: After informed consent, eight adult patients with OME were included in this study. After investigated patients' case history and oto-function, all patients underwent BDET treatment. Then four criteria including tympanic membrane, pure tone audiometry (PTA), tympanometry, and subjective symptoms were adopted to evaluate the therapeutic benefits of BDET. RESULTS: None of the involved patients complained of problems or complications during the post-operative period, or with absence of pain and bleeding after the operation. Prominent post-operative improvement was observed in tympanic membrane and otoscopic appearance. In addition, cure rates after 3 months and 6 months post-operatively were gradually increased.

Significance of ATP-binding cassette transporter proteins in multidrug resistance of head and neck squamous cell carcinoma.

According to the cancer stem cell theory, a small subpopulation of cancer cells, known as cancer stem cells (CSCs), exist that are self-renewing and are involved in tumor invasion, metastasis and recurrence. A number of studies have reported that certain cancer cells are able to efflux the Hoechst 33342 dye. These cells are termed side population (SP) cells and share characteristic features of CSCs. The results of the present study revealed that 2.7% of primary head and neck squamous cell carcinoma (HNSCC) cells were SP cells. This was reduced to 0.7% following treatment with verapamil. The immunofluorescence and reverse transcription polymerase chain reaction analysis revealed that SP cells have an enhanced expression of the ATP-binding cassette (ABC) transporter protein ABC subfamily G, member 2 (ABCG2), which has been identified to be actively involved in drug exclusion. Similarly, the mRNA level of the oncogene B lymphoma Mo-MLV insertion region-1 and the stem cell surface proteins nestin and octamer-binding transcription factor-4 were highly expressed in the SP cells compared with the non-SP cells. In addition, it was demonstrated that HNSCC SP cells exhibited increased proliferation and were highly resistant to multiple drugs. These findings suggest that the presence of CSCs, such as SP cells, may be responsible for chemotherapy failure and tumor relapse in patients with HNSCC. Therefore, the identification of a novel therapeutic drug that could effectively target CSCs may help to eradicate refractory tumors.

Prognostic value of TROP2 in human nasopharyngeal carcinoma.

BACKGROUND: There is increasing evidence demonstrating the role of human trophoblast cell surface antigen 2 (TROP2) in cancer development and progression. However, their prognostic value in Epstein-Barr virus (EBV) associated nasopharyngeal carcinoma (NPC) remains to be elucidated. METHOD: The prognostic significances of TROP2 and Ki-67 were determined by immunohistochemistry in 58 NPC samples. TROP2 mRNA expression level and biological functions were evaluated. The presence of EBV was assessed using in situ hybridization. Analyses were conducted on the association between each of these variables as well as clinical outcome. RESULTS: TROP2 was exhibited over expression in 64% of NPC samples and significantly associated with highly proliferative tumor cells (P = 0.05) and lymph node metastases (P = 0.03). Overexpression of TROP2 significantly correlated with worse overall survival (P = 0.026) and poor disease-free survival (P = 0.021). By univariate analysis, high expression of TROP2 significantly correlated with patients with distant metastases, Ki-67 and EBV infection. Multivariate analysis further revealed that TROP2 along with Ki-67 and distant metastasis are independent prognostic predictors for NPC patients. CONCLUSION: Our findings have demonstrated that overexpression of TROP2 appears to be an independent predictor for poor clinical outcome in NPC. The strong correlation of overexpression of TROP2 with Ki-67 and distant metastases indicates a potentially therapeutic strategies targeting TROP2 for NPC patients.

Constitutive secretion of Interleukin-4 dictates CD133+ side population cells to resist drug treatment and cell death.

PURPOSE: In the present study, we made an attempt to elucidate the role of oversecretion of interleukin-4 (IL-4) in cancer stem cells (CSCs) of head and neck squamous cell carcinoma (HNSCC). METHODS: HNSCC samples were analyzed for the presence of CSCs by flow cytometry. In addition, we have performed drug and apoptosis resistance assays to determine the role of IL-4 in CSCs. RESULTS: HNSCC samples contained 3.3% of CD133+ cancer stem like side population (SP) cells in HNSCC which displayed infinite cell proliferation and they had high self-renewal capacity. These CD133+ cells displayed enhanced expression of IL-4, which promoted multidrug and apoptosis resistance. After neutralizing IL-4, the CD133+ SP cells became more sensitive to drug treatment and apoptosis. CONCLUSIONS: Our data suggest that the autocrine secretion of IL-4 is a potential target for the development of novel anticancer drugs to prevent the CSCs-mediated therapy failure and tumorigenesis.

Abnormal Wnt signaling and overexpression of ABCG2 contributes to drug efflux properties of side population cells in nasopharyngeal carcinoma.

The presence of cancer stem cells (CSCs) has major implications in the choice of cancer treatment strategy and is responsible for tumor relapse. CSCs have been isolated and characterized in several types of cancer; however, studies concerning the CSCs from nasopharyngeal carcinoma (NPC) are limited. Thus, the present study was designed to isolate and characterize the cancer stem-like side population (SP) cells from NPC samples. The fluorescence-activated cell sorting (FACS)-based Hoechst 33342 dye exclusion technique identified that 3.9% of cells from NPC samples were cancer stem-like SP cells. Upon treatment with verapamil (ABC transporter inhibitor), the percentage of SP cells was significantly reduced to 0.7%, which confirms that the ABC transporter protein exhibits a significant role in drug exclusion. Fluorescence microscopy analysis revealed that the FACS purified SP cells showed increased expression of ABCG2 (ATP transporter protein), Oct-4 and CD44 (stem cell surface protein). Furthermore, these SP cells exhibited increased mRNA expression of ABCG2 and anti-apoptotic factor Bmi-1, which contribute to multi-drug resistance and increased cell survival rate. Notably, the Wnt/ß-catenin signaling pathways are altered in SP cells. In addition, using reverse transcription­quantitative polymerase chain reaction analysis it was observed that the cells exhibited increased expression of DKK1 and AXIN2. In conclusion, data from the present study clearly demonstrated that the presence of cancer stem-like SP cells from NPC may be responsible for chemotherapeutic drug resistance, tumor recurrence and invasion.

Gene expression profiling via bioinformatics analysis reveals biomarkers in laryngeal squamous cell carcinoma.

The present study aimed to identify key genes and relevant microRNAs (miRNAs) involved in laryngeal squamous cell carcinoma (LSCC). The gene expression profiles of LSCC tissue samples were analyzed with various bioinformatics tools. A gene expression data set (GSE51985), including ten laryngeal squamous cell carcinoma (LSCC) tissue samples and ten adjacent non-neoplastic tissue samples, was downloaded from the Gene Expression Omnibus. Differential analysis was performed using software package limma of R. Functional enrichment analysis was applied to the differentially expressed genes (DEGs) using the Database for Annotation, Visualization and Integrated Discovery. Protein-protein interaction (PPI) networks were constructed for the protein products using information from the Search Tool for the Retrieval of Interacting Genes/Proteins. Module analysis was performed using ClusterONE (a software plugin from Cytoscape). MicroRNAs (miRNAs) regulating the DEGs were predicted using WebGestalt. A total of 461 DEGs were identified in LSCC, 297 of which were upregulated and 164 of which were downregulated. Cell cycle, proteasome and DNA replication were significantly over-represented in the upregulated genes, while the ribosome was significantly over-represented in the downregulated genes. Two PPI networks were constructed for the up- and downregulated genes. One module from the upregulated gene network was associated with protein kinase. Numerous miRNAs associated with LSCC were predicted, including miRNA (miR)-25, miR-32, miR-92 and miR-29. In conclusion, numerous key genes and pathways involved in LSCC were revealed, which may aid the advancement of current knowledge regarding the pathogenesis of LSCC. In addition, relevant miRNAs were also identified, which may represent potential biomarkers for use in the diagnosis or treatment of the disease.

Salmonella typhimurium mediated delivery of Apoptin in human laryngeal cancer.

An effective cancer therapeutic should target tumours specifically with limited systemic toxicity. Here, we transformed an attenuated Salmonella typhimurium (S. typhimurium) with an Apoptin expressing plasmid into a human laryngeal carcinoma cell line. The expression of the inserted gene was measured using fluorescence and immunoblotting assays. The attenuated S. typhimurium-mediated Apoptin significantly decreased cytotoxicity and strongly increased cell apoptosis through the activation of caspase-3. The process was mediated by Bax, cytochrome c and caspase-9. A syngeneic nude murine tumour model was used to determine the anti-tumour effects of the recombinant bacteria in vivo. Systemic injection of the recombinant bacteria with and without re-dosing caused significant tumour growth delay and reduced tumour microvessel density, thereby extending host survival. Our findings indicated that the use of recombinant Salmonella typhimurium as an Apoptin expression vector has potential cancer therapeutic benefits.