Silencing geranylgeranyltransferase I inhibits the migration and invasion of salivary adenoid cystic carcinoma through RhoA/ROCK1/MLC signaling and suppresses proliferation through cell cycle regulation.

Geranylgeranyltransferase type I (GGTase-I) significantly affects Rho proteins, such that the malignant progression of several cancers may be induced. Nevertheless, the effect and underlying mechanism of GGTase-I in the malignant progression of salivary adenoid cystic carcinoma (SACC) remain unclear. This study primarily aimed to investigate the role and mechanism of GGTase-I in mediating the malignant progression of SACC. The level of GGTase-I gene in cells was stably knocked down by short hairpin RNA-EGFP-lentivirus. The effects of GGTase-I silencing on the migration, invasion, and spread of cells were examined, the messenger RNA levels of GGTase-I and RhoA genes of SACC cells after GGTase-I knockdown were determined, and the protein levels of RhoA and RhoA membrane of SACC cells were analyzed. Moreover, the potential underlying mechanism of silencing GGTase-I on the above-mentioned aspects in SACC cells was assessed by examining the protein expression of ROCK1, MLC, p-MLC, E-cadherin, Vimentin, MMP2, and MMP9. Furthermore, the underlying mechanism of SACC cells proliferation was investigated through the analysis of the expression of cyclinD1, MYC, E2F1, and p21CIP1/WAF1 . Besides, the change of RhoA level in SACC tissues compared with normal paracancer tissues was demonstrated through quantitative reverse-transcription polymerase chain reaction and western blot experiments. Next, the effect after GGTase-I silencing was assessed through the subcutaneous tumorigenicity assay. As indicated by the result of this study, the silencing of GGTase-I significantly reduced the malignant progression of tumors in vivo while decreasing the migration, invasion, and proliferation of SACC cells and RhoA membrane, Vimentin, ROCK1, p-MLC, MMP2, MMP9, MYC, E2F1, and CyclinD1 expression. However, the protein expression of E-cadherin and p21CIP1/WAF1 was notably upregulated. Subsequently, no significant transform of RhoA and MLC proteins was identified. Furthermore, RhoA expression in SACC tissues was significantly higher than that in paracancerous tissues. As revealed by the results of this study, GGTase-I shows a correlation with the proliferation of SACC through the regulation of cell cycle and may take on vital significance in the migration and invasion of SACC by regulating RhoA/ROCK1/MLC signaling pathway. GGTase-I is expected to serve as a novel exploration site of SACC.

Neural stem cell-derived exosomal FTO protects neuron from microglial inflammatory injury by inhibiting microglia NRF2 mRNA m6A modification.

Ischemic stroke (IS) can cause neuronal cell loss and function defects. Exosomes derived from neural stem cells (NSC-Exos) improve neural plasticity and promote neural function repair following IS. However, the potential mechanism remains unclear. In this study, NSC-Exos were characterized and co-cultured with microglia. We found that NSC-Exos increased NRF2 expression in oxygen-glucose deprivation/reoxygenation and LPS-induced microglia and converted microglia from M1 pro-inflammatory phenotype to M2 anti-inflammatory phenotype. NSC-Exos reduced m6A methylation modification of nuclear factor erythroid 2-related factor 2 (NRF2) mRNA via obesity-associated gene (FTO). Furthermore, NSC-Exos reduced the damage to neurons caused by microglia's inflammatory response. Finally, the changes in microglia polarization and neuron damage caused by FTO knockdown in NSE-Exos were attenuated by NRF2 overexpression in microglia. These findings revealed that NSC-Exos promotes NRF2 expression and M2 polarization of microglial via transferring FTO, thereby resulting in neuroprotective effects.

SS31 Confers Cerebral Protection by Reversing Mitochondrial Dysfunction in Early Brain Injury Following Subarachnoid Hemorrhage, via the Nrf2- and PGC-1α-Dependent Pathways.

In early brain injury (EBI), oxidative stress occurs following subarachnoid hemorrhage (SAH), and mitochondria are intricately linked to this process. SS31, a mitochondria-targeting antioxidative peptide, has been demonstrated to be beneficial for multiple diseases because of its powerful antioxidant and neuroprotective properties. Although our previous study revealed that SS31 was involved in the powerful antioxidant effect following SAH, the underlying molecular mechanisms remained unclear. Thus, our study aimed to investigate the neuroprotective effects of SS31 by reversing mitochondrial dysfunction in EBI following SAH, via activating the Nrf2 signaling and PGC-1α pathways. Our findings confirmed that SS31 ameliorated SAH-triggered oxidative insult. SS31 administration decreased redundant reactive oxygen species, alleviated lipid peroxidation, and elevated the activities of antioxidant enzymes. Concomitant with the inhibited oxidative insult, SS31 dramatically attenuated neurological deficits, cerebral edema, neural apoptosis, and blood-brain barrier disruption following SAH. Moreover, SS31 remarkably promoted nuclear factor-erythroid 2 related factor 2 (Nrf2) nuclear shuttle and upregulated the expression levels of heme oxygenase-1 and NADPH: quinine oxidoreductase1. Additionally, SS31 enhanced the expression levels of PGC-1α and its target genes, and increased the mtDNA copy number, promoting mitochondrial function. However, PGC-1α-specific inhibitor SR-18292 pretreatment dramatically suppressed SS31-induced Nrf2 expression and PGC-1α activation. Furthermore, pretreatment with SR-18292 reversed the neuroprotective and antioxidant roles of SS31. These significant beneficial effects were associated with the activation of the Nrf2 signaling and PGC-1α pathways and were antagonized by SR-18292 administration. Our findings reveal that SS31 exhibits its neuroprotective activity by reversing mitochondrial dysfunction via activating the Nrf2 signaling pathway, which could be mediated through PGC-1α activation.

Demethylase FTO promotes mechanical stress induced osteogenic differentiation of BMSCs with up-regulation of HIF-1α.

BACKGROUND: In orthodontics, mechanical stress plays an important role in the process of bone remodeling. Mechanical stress has an effect on osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs). However, the mechanism remains to be studied. The aim of this study is to investigate the effects of demethyltransferase fat mass and obesity-associated (FTO) on osteogenic differentiation of BMSCs under mechanical stress condition. METHODS AND RESULTS: The rat BMSCs were cultured in vitro, followed by flow cytometry to identify the cell surface antigens. Osteogenic differentiation of BMSCs was induced by mechanical stress by using the flexcell tension system for 6 h every day and 3 days in total. BMSCs were transfected by using plasmid for FTO knockdown. The expression level of FTO, hypoxia-inducible factor (HIF)-1α, runt-related transcription factor 2 (RUNX2), bone morphogenetic proteins (BMPs) and alkaline phosphatase (ALP) were measured by real-time qPCR, western blotting. ALP activity were determined by ALP staining assays. The expression of FTO and HIF-1α in BMSCs with mechanical stress were significantly higher than BMSCs without mechanical stress, also, the expression of osteogenic differentiation markers were higher in BMSCs with mechanical stress. Knockdown of FTO decreased expression of osteogenic differentiation marker and ALP activity in stretched BMSCs. In addition, the expression of HIF-1α was decreased after knocking down FTO. CONCLUSIONS: FTO promotes the expression of HIF-1α and osteogenic differentiation under the condition of mechanical stress. This finding may facilitate the clinical application of orthodontics and the mechanism research of mechanical stress-induced osteogenesis.

Cleavage of caspase-12 at Asp94, mediated by endoplasmic reticulum stress (ERS), contributes to stretch-induced apoptosis of myoblasts.

Mechanical overloading can lead to skeletal muscle damage instead of remodeling. This is attributed to the excessive apoptosis of myoblasts, mechanism of which remains to be elucidated. The present study aimed to investigate the involvement of endoplasmic reticulum stress (ERS) and caspase-12 in mediating the stretch-induced apoptosis of myoblasts. Myoblast apoptosis was evaluated by Hoechst staining, DNA fragmentation assay, Annexin V binding, and propidium iodide staining, as well as caspase-3 and poly-ADP-ribose polymerase 1 cleavage. First, our results showed that apoptosis was elevated in a time-dependent manner when myoblasts were subjected to cyclic mechanical stretch (CMS) for 12, 24, and 36 hr. Concomitantly, CMS triggered the ERS and caspase-12 cleavage; ERS inhibitor GSK 2606414 suppressed the CMS-induced cleavage of caspase-12 and myoblast apoptosis. Silencing caspase-12 attenuated the apoptosis of myoblasts under CMS. Furthermore, CMS-induced myoblast apoptosis was partially recovered by overexpressing wild-type caspase-12 in caspase-12-silenced myoblasts. In contrast, overexpressing mutant caspase-12 (D94N), which cannot be cleaved into the active caspase-12 fragments, failed to accomplish the same effect. Finally, C2C12 overexpressing truncated caspase-12 segment (TC-casp12-D94), which starts from Asp94 and ends at Asn419, underwent apoptosis under both static and stretched conditions. Interestingly, C2C12 myoblasts seemed to be resistant to stretch-induced apoptosis upon low-serum-induced differentiation. In conclusion, our study provided evidence that caspase-12 cleavage at Asp94, induced by ERS under mechanical stimuli, is the key molecule in initiating the stretch-triggered apoptosis of myoblasts.

[Protective effect of mitochondria-targeted antioxidant SS31 on early brain injury following subarachnoid hemorrhage in rats].

OBJECTIVE: To evaluate protective effects of SS31 on early brain injury (EBI) induced by subarachnoid hemorrhage (SAH) in rats.
 Methods: A total of 96 Sprague-Dawley rats were randomly divided into 4 groups: A sham group, an SAH group, an SAH+vehicle group (SAH+V), and an SAH+SS31 group. The SAH-induced prechiasmatic cistern rat model was established in this study. Neurological deficit scores were evaluated at 24 h after SAH. The SS31 (5 mg/kg) as well as equal volume of vehicle were administrated intraperitoneally at 2 h after SAH. The neurological scores, brain edema, blood-brain barrier (BBB) permeability, apoptosis, malondialdehyde (MDA), glutathione peroxidase (GPx) activity, superoride dismutase (SOD) activity, and the expression of cytosolic cytochrome c (Cyt C) and Bax were analyzed at 24 h after SAH.
 Results: Treatment with SS31 could significantly reduce MDA levels, and restored the activities of GPx and SOD in the cortex following SAH when compared with the SAH+V group. In addition, Bax SS31 trearment increased or decreased the levels of mitochondrial Cyt C or Bax, respectively. Moreover, SS31 treatment ameliorated brain edema and Evans blue dye extravasation, improved neurological deficits, and decreased neuronal apoptosis at 24 h after SAH.
 Conclusion: SS31 could alleviate EBI after SAH through its antioxidant property and ability in inhibition of neuronal apoptosis.

[MiR-26b inhibits proliferation, invasion, and migration of glioma by targeting cyclooxygenase-2].

OBJECTIVE: To explore the expressions of miR-26b and cyclooxygenase (COX)-2 in different grades of gliomas and the effect of miR-26b on glioma cell proliferation, invasion and migration.
 Methods: Western blot and Real-time quantitative PCR (qRT-PCR) were used to detect the expression levels of miR-26b and COX-2 in different grades of gliomas. Human glioma cells were transfected with miR-26b mimics. qRT-PCR was employed to detect the mRNA expressions of miR-26b and COX-2 after miR-26b mimics transfection, while dual-luciferase reporter assay was used to investigate the regulatory effect of miR-26b on COX-2. Cell counting kit-8 (CCK8), trans-well invasion assay and scratch assay were used to detect the proliferation, invasion and migration of human U87 glioma cells after miR-26b mimic transfection, respectively. The antitumor effect of miR-26b was verified by evaluating the volume and weight of tumor in nude mice.
 Results: With the increase in tumor grades, the expression of miR-26b was significantly decreased (P<0.05), while COX-2 expression was increased (P<0.001). Dual luciferase assay confirmed that miR-26b could directly regulate the protein expression of COX-2. MiR-26b mimics could significantly reduce the expression of COX-2 (P<0.05) and suppress the proliferation, invasion and migration of glioma cell (P<0.05). The volume and weight of tumor in MiR-26b mimics transfection group were smaller than those in the control group.
 Conclusion: Overexpression of miR-26b may inhibit proliferation, invasion, and migration of glioma by suppressing the expression of COX-2. Therefore, the miR-26b/COX-2 pathway might be a therapeutic target in glioma.

[Construction and identification of a lentiviral vector for RNA interference of human GLUT3 gene].

OBJECTIVE: To construct an effective lentiviral vector for RNA interference (RNAi) with human glucose transporter 3 (GLUT3)gene.
 METHODS: Four pairs of shRNA sequences against different parts of GLUT3-mRNA were separately cloned into the RNAi plasmid vector pLV-shRNA by recombinant DNA technology to construct shRNA expression vectors pLV-shRNA-GLUT3-1, pLV-shRNA-GLUT3-2, pLV-shRNA-GLUT3-3, and pLV-shRNA-GLUT3-4. The vectors were transfected into HeLa cells to detect the effectiveness of GLUT3 gene silencing. One of effective vectors was selected and co-transfected into 293T cells with lentivirus packaging plasmids to obtain packaged lentivirus particles LV-GLUT3. After viral titer determination, U251 glioblastoma cells were infected with LV-GLUT3 at a multiplicity of infection (MOI) of 10. Finally, the expression of GLUT3 protein was detected by Western blot. 
 RESULTS: DNA sequencing demonstrated that the shRNA sequences were successfully inserted into the pLV-shRNA vectors. In HeLa cells, the expression of GLUT3-mRNA was significantly down-regulated by the recombinant vectors compared with negative control. The recombinant lentivirus LV-GLUT3 harvested from 293T cells had a titer of 1.5×10(9) TU/mL. After infection with LV-GLUT3, the expression of GLUT3 protein in U251 glioblastoma cells was down-regulated. 
 CONCLUSION: An effective lentiviral shRNA expression vector targeting the GLUT3 gene is successfully constructed and can be used for further study on the functions of GLUT3 gene.

Silencing RhoA inhibits migration and invasion through Wnt/ß-catenin pathway and growth through cell cycle regulation in human tongue cancer.

Ras homolog gene family member A (RhoA) has been identified as a critical regulator of tumor aggressive behavior. In this study, we assessed the role of RhoA in the mechanisms underlying growth, migration, and invasion of squamous cell carcinoma of tongue (TSCC). Stable RhoA knockdown of TSCC cell lines SCC-4 and CAL27 were achieved using Lentiviral transfection. The effects of RhoA depletion on cell migration, invasion, and cell proliferation were determined. The possible underlying mechanism of RhoA depletion on TSCC cell line was also evaluated by determining the expression of Galectin-3 (Gal-3), ß-catenin, and matrix metalloproteinase-9 (MMP-9) in vivo. Meanwhile, the underlying mechanism of TSCC growth was studied by analysis of cyclin D1/2, p21CIP1/WAF1, and p27Kip1 protein levels. Immunohistochemical assessments were performed to further prove the alteration of Gal-3 and ß-catenin expression. We found that, in mice injected with human TSCC cells in the tongue, RhoA levels were higher in primary tumors and metastasized lymph nodes compared with those in the normal tissues. Silencing of RhoA significantly reduced the tumor growth, decreased the levels of Gal-3, ß-catenin, MMP-9, and cyclin D1/2, and increased the levels of p21CIP1/WAF1 and p27Kip1. In vitro, RhoA knockdown also led to inhibition of cell migration, invasion, and proliferation. Our data suggest that RhoA plays a significant role in TSCC progression by regulating cell migration and invasion through Wnt/ß-catenin signaling pathway and cell proliferation through cell cycle regulation, respectively. RhoA might be a novel therapeutic target of TSCC.

Exploration of the shared diagnostic genes and mechanisms between periodontitis and primary Sjögren's syndrome by integrated comprehensive bioinformatics analysis and machine learning.

BACKGROUND: Accumulating evidence has showed a bidirectional link between periodontitis (PD) and primary Sjögren's syndrome (pSS), but the mechanisms of their occurrence remain unclear. Hence, this study aimed to investigate the shared diagnostic genes and potential mechanisms between PD and pSS using bioinformatics methods. METHODS: Gene expression data for PD and pSS were acquired from the Gene Expression Omnibus (GEO) database. Differential expression genes (DEGs) analysis and weighted gene co-expression network analysis (WGCNA) were utilized to search common genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were conducted to explore biological functions. Three machine learning algorithms (least absolute shrinkage and selection operator (LASSO), support vector machine recursive feature elimination (SVM-RFE), and random forest (RF)) were used to further identify shared diagnostic genes, and these genes were assessed via receiver operating characteristic (ROC) curves in discovery and validation datasets. CIBERSORT was employed for immune cell infiltration analysis. Transcription factors (TFs)-genes and miRNAs-genes regulatory networks were conducted by NetworkAnalyst. Finally, relevant drug targets were predicted by DSigDB. RESULTS: Based on DEGs, 173 overlapping genes were obtained and primarily enriched in immune- and inflammation-related pathways. WGCNA revealed 34 common disease-related genes, which were enriched in similar biological pathways. Intersecting the DEGs with WGCNA results yielded 22 candidate genes. Moreover, three machine learning algorithms identified three shared genes (CSF2RB, CXCR4, and LYN) between PD and pSS, and these genes demonstrated good diagnostic performance (AUC>0.85) in both discovery and validation datasets. The immune cell infiltration analysis showed significant dysregulation in several immune cell populations. Regulatory network analysis highlighted that WRNIP1 and has-mir-155-5p might be pivotal co-regulators of the three shared gene expressions. Finally, the top 10 potential gene-targeted drugs were screened. CONCLUSION: CSF2RB, CXCR4, and LYN may serve as potential biomarkers for the concurrent diagnosis of PD and pSS. Additionally, we identified common molecular mechanisms, TFs, miRNAs, and candidate drugs between PD and pSS, which may provide novel insights and targets for future research on the pathogenesis, diagnosis, and therapy of both diseases.

P4HA2 promotes proliferation, invasion, and metastasis through regulation of the PI3K/AKT signaling pathway in oral squamous cell carcinoma.

Proline 4-hydroxylase 2 (P4HA2) is known for its hydroxylase activity, primarily involved in hydroxylating collagen precursors and promoting collagen cross-linking under physiological conditions. Although its overexpression influences a wide variety of malignant tumors' occurrence and development, its specific effects and mechanisms in oral squamous cell carcinoma (OSCC) remain unclear. This study focused on investigating the expression patterns, carcinogenic functions, and underlying mechanisms of P4HA2 in OSCC cells. Various databases, including TCGA, TIMER, UALCAN, GEPIA, and K-M plotter, along with paraffin-embedded samples, were used to ascertain P4HA2 expression in cancer and its correlation with clinicopathological features. P4HA2 knockdown and overexpression cell models were developed to assess its oncogenic roles and mechanisms. The results indicated that P4HA2 was overexpressed in OSCC and inversely correlated with patient survival. Knockdown of P4HA2 suppressed invasion, migration, and proliferation of OSCC cells both in vitro and in vivo, whereas overexpression of P4HA2 had the opposite effects. Mechanistically, the phosphorylation levels of the PI3K/AKT pathway were reduced following P4HA2 silencing. The study reveals that P4HA2 acts as a promising biomarker for predicting prognosis in OSCC and significantly affects metastasis, invasion, and proliferation of OSCC cells through the regulation of the PI3K/AKT signaling pathway.

SCGB1A1 as a novel biomarker and promising therapeutic target for the management of HNSCC.

Head and neck cancer (HNC) is the sixth most common type of cancer worldwide, and head and neck squamous cell carcinoma (HNSCC) accounts for 90% of HNC cases. Furthermore, HNSCC accounts for 400,000 cancer-associated deaths worldwide each year. However, at present there is an absence of a versatile biomarker that can be used for diagnosis, prognosis evaluation and as a therapeutic target for HNSCC. In the present study, bioinformatics analysis was used to assess the relationship between hub genes and the clinical features of patients with HNSCC. The findings from the bioinformatics analysis were then verified using clinical samples and in vitro experiments. A total of 51 overlapping genes were identified from the intersection of differentially expressed genes and co-expressed genes. The top 10 hub genes were obtained from a protein-protein interaction network of overlapping genes. Among the hub genes, only secretoglobin family 1A member 1 (SCGB1A1) was significantly associated with both overall and disease-free survival. Specifically, upregulated SCGB1A1 expression levels were associated with prolonged overall and disease-free survival. Moreover, the SCGB1A1 expression levels were negatively correlated with drug sensitivity. Notably, it was demonstrated that SCGB1A1 was involved in tumor immunoreaction by affecting the infiltration of cells and checkpoint regulation of immune cells. Additionally, it was shown that SCGB1A1 regulated multiple key cancer-related signaling pathways, including extracellular matrix receptor interaction, transforming growth factor-ß and tumor metabolism signaling pathways. Based on the results of the present study, SCGB1A1 may serve as a novel biomarker for predicting the diagnosis, prognosis and therapeutic effectiveness of certain drugs in patients with HNSCC. Moreover, SCGB1A1 may serve as a potential therapeutic target for the management of HNSCC.

Galectin-3 gene silencing inhibits migration and invasion of human tongue cancer cells in vitro via downregulating ß-catenin.

AIM: Galectin-3 (Gal-3) is a member of the carbohydrate-binding protein family that contributes to neoplastic transformation, tumor survival, angiogenesis, and metastasis. The aim of this study is to investigate the role of Gal-3 in human tongue cancer progression. METHODS: Human tongue cancer cell lines (SCC-4 and CAL27) were transfected with a small-interfering RNA against Gal-3 (Gal-3-siRNA). The migration and invasion of the cells were examined using a scratch assay and BD BioCoat Matrigel Invasion Chamber, respectively. The mRNA and protein levels of ß-catenin, Akt/pAkt, GSK-3ß/pGSK-3ß, MMP-9 in the cells were measured using RT-PCR and Western blotting, respectively. RESULTS: Transient silencing of Gal-3 gene for 48 h significantly suppressed the migration and invasion of both SCC-4 and CAL27 cells. Silencing of Gal-3 gene significantly decreased the protein level of ß-catenin, leaving the mRNA level of ß-catenin unaffected. Furthermore, silencing Gal-3 gene significantly decreased the levels of phosphorylated Akt and GSK-3ß, and suppressed the mRNA and protein levels of MMP-9 in the cells. CONCLUSION: Our data suggest that Gal-3 mediates the migration and invasion of tongue cancer cells in vitro via regulating the Wnt/ß-catenin signaling pathway and Akt phosphorylation.

Targeting the protein prenyltransferases efficiently reduces tumor development in mice with K-RAS-induced lung cancer.

RAS and RHO proteins, which contribute to tumorigenesis and metastasis, undergo posttranslational modification with an isoprenyl lipid by protein farnesyltransferase (FTase) or protein geranylgeranyltransferase-I (GGTase-I). Inhibitors of FTase and GGTase-I were developed to block RAS-induced malignancies, but their utility has been difficult to evaluate because of off-target effects, drug resistance, and toxicity. Moreover, the impact of FTase deficiency and combined FTase/GGTase-I deficiency has not been evaluated with genetic approaches. We found that inactivation of FTase eliminated farnesylation of HDJ2 and H-RAS, prevented H-RAS targeting to the plasma membrane, and blocked proliferation of primary and K-RAS(G12D)-expressing fibroblasts. FTase inactivation in mice with K-RAS-induced lung cancer reduced tumor growth and improved survival, similar to results obtained previously with inactivation of GGTase-I. Simultaneous inactivation of FTase and GGTase-I markedly reduced lung tumors and improved survival without apparent pulmonary toxicity. These data shed light on the biochemical and therapeutic importance of FTase and suggest that simultaneous inhibition of FTase and GGTase-I could be useful in cancer therapeutics.

Microbial dysbiosis in oral squamous cell carcinoma: A systematic review and meta-analysis.

Objective: The aim of this study was to summarize previously published data and assess the alterations in the composition of the oral microbiome in OSCC using a systematic review and meta-analysis. Design: Electronic databases were systematically searched for studies on the oral microbiome in OSCC published before December 2021. Qualitative assessments of compositional variations at the phylum level were performed. The meta-analysis on abundance changes of bacteria genera was performed via a random-effects model. Results: A total of 18 studies involving 1056 participants were included. They consisted of two categories of studies: 1) case-control studies (n = 9); 2) nine studies that compared the oral microbiome between cancerous tissues and paired paracancerous tissues. At the phylum level, enrichment of Fusobacteria but depletion in Actinobacteria and Firmicutes in the oral microbiome was demonstrated in both categories of studies. At the genus level, Fusobacterium showed an increased abundance in OSCC patients (SMD = 0.65, 95% CI: 0.43-0.87, Z = 5.809, P = 0.000) and in cancerous tissues (SMD = 0.54, 95% CI: 0.36-0.72, Z = 5.785, P = 0.000). The abundance of Streptococcus was decreased in OSCC (SMD = -0.46, 95% CI: -0.88-0.04, Z = -2.146, P = 0.032) and in cancerous tissues (SMD = -0.45, 95% CI: -0.78-0.13, Z = -2.726, P = 0.006). Conclusions: Disturbances in the interactions between enriched Fusobacterium and depleted Streptococcus may participate in or prompt the occurrence and development of OSCC and could be potential biomarkers for detection of OSCC.

Current status of research on emergency surgery score in trauma patients: a bibliometric analysis.

Background: The use of a relevant emergency score can provide an accurate assessment of the patient's condition and prognosis. However, the status of related studies remains unclear. The current study analyzed the research status of emergency surgery score (ESS) of trauma patients by using bibliometric methods. Methods: The Science Citation Index Expanded (SCI-E) database in the Web of Science Core Collection (WOSCC) was searched using keywords "trauma" and "emergency surgery score". All records from the search results and cited references were exported to Excel, duplicate literature records were removed, information for the same author and organization in different signature forms were merged. The resulting literatures were analyzed by year of publication, citation, discipline, countries and research institutions, journals, authors, and use of keywords. The cooperation among countries, institutions, and authors was also examined. Results: A total of 2,175 document were retrieved. The number of published literature and the number of citations per year increased annually. The number of published documents (n=1,029) and research cooperation (centrality score, 0.44) in the United States were significantly ahead of those in other countries. The ten research institutions with the largest number of published documents were all from the United States, with much cooperation between research institutions and authors. There were many publications from China (n=108), but with few cooperations (centrality score, 0.22). The journals with the largest number of published articles were professional in the fields of trauma, emergency, and critical care. Keyword analysis showed that infection and shock were important issues besides surgery in the research related to ESS of trauma patients. Conclusions: Research related to ESS of trauma patients has been mainly conducted in the United States, and Chinese researchers should increase their level of cooperation.

Effects of silencing farnesyltransferase on the migration, invasion, and epithelial-mesenchymal transition of salivary adenoid cystic carcinoma cells.

OBJECTIVES: This study aimed to investigate the effects of farnesyltransferase (FTase) on the migration, invasion, and epithelial-mesenchymal transition (EMT) of SACC-LM and SACC-83 cells in salivary adenoid cystic carcinoma and determine the relative mechanism. METHODS: Three small interfering RNA (siRNA) sequences were designed and constructed based on the human FTase gene sequence. The SACC-LM and SACC-83 cells in the logarithmic growth period were used, and the expression of FTase was suppressed by liposomal transient transfection. The tested cells were categorized as the FTase-siRNA-1, FTase-siRNA-2, and FTase-siRNA-3 groups. Both negative control group (NC-siRNA) and blank control group (only transfection reagent was added) were set. The mRNA expression of FTase and HRAS was detected by quantitive real-time polymerase chain reaction, and the silencing efficiency was determined. The expression levels of FTase, HRAS, protein kinase B (AKT), phospho-AKT, p65, phospho-p65 (Ser563), E-cadherin, vimentin, matrix metalloproteinase (MMP)-9 protein, and HRAS membrane protein were detected by Western blot. Transwell assay and wound healing assay were used to detect the invasion and migration abilities of cells. RESULTS: The relative expression of FTase mRNA and protein in the FTase-siRNA-1 group decreased compared with those in the control group (P<0.05). HRAS mRNA and total protein expression had no significant difference (P>0.05), and the relative expression of HRAS membrane protein decreased (P<0.05). The relative expression of E-cadherin increased (P<0.05), vimentin decreased (P<0.05), and MMP-9 decreased (P<0.05). There was no significant difference in the relative expression levels of the RAS/PI3K/AKT/nuclear factor-κB signaling pathway-related proteins AKT and p65 (P>0.05), but the relative expression levels of phospho-AKT and phospho-p65 decreased. The invasion and migration ability of the FTase-siRNA-1 group significantly decreased compared with that in the control group (P<0.05). CONCLUSIONS: Silencing FTase in vitro could effectively inhibit the invasion and migration of SACC-LM and SACC-83 cells by interfering with the localization of the HRAS membrane protein and regulating the RAS/PI3K/AKT/nuclear factor-κB signaling pathway to mediate EMT.

FOXM1 is regulated by DEPDC1 to facilitate development and metastasis of oral squamous cell carcinoma.

The Disheveled, EGL-10, Pleckstrin domain containing 1 (DEPDC1) is a new oncogene that has recently been described. The mechanisms and functions of its expression are yet to be determined in oral squamous cell carcinoma (OSCC). In the present study, the impact of DEPDC1 on the growth and development of OSCC was investigated using animal models, cell lines and human tissue samples. Elevated DEPDC1 expression within cancer cell lines and human OSCC has been identified. Mechanistic examination showed that restored DEPDC1 expression in vivo and in vitro stimulated OSCC tumour development. In addition, FOXM1 interacts with DEPDC1 as indicated by co-immunoprecipitation and immunofluorescence testing. Functionally, DEPDC1 facilitated Wnt/ß-catenin signal transduction and ß-catenin protein nuclear expression. In summary, the DEPDC1, interacting with FOXM1 via Wnt/ß-catenin signaling, the closely regulated OSCC pathogenesis, suggesting that targeting the novel DEPDC1/FOXM1/ß-catenin complex is an essential OSCC therapeutic approach.