Study on the mechanism of 20-hydroxyeicosatetraenoic acid in retinal ischemia-reperfusion injury.

PURPOSE: To explore the effect of 20-hydroxyeicosatetraenoic acid (20-HETE) on retinal ischemia-reperfusion injury (RIRI) and the protective effect of N-hydroxy-N'-(4-n-butyl-2-methylphenyl)formamidine (HET0016) on RIRI. METHODS: Male Sprague-Dawley rats were randomly divided into the normal control group, experimental model group (RIRI group), experimental solvent group (RIRI + solvent group), and experimental treatment group (RIRI + HET0016 group). RESULTS: The levels of 20-HETE, tumor necrosis factor-α (TNF-α), and interleukin-1ß (IL-1ß) in the retina of rats at 24 h after reperfusion were measured by enzyme-linked immunosorbent assay. Hematoxylin-eosin staining was used to observe the retinal morphological and thickness changes at 24 h, 48 h, and 7 days after reperfusion. The number and localized expression of matrix metalloproteinase-9-positive cells in the retina of the rats at 24 h after reperfusion and the activation and localized expression of retinal microglia at 48 h after reperfusion were measured using an immunohistochemical method. The nuclear metastasis of nuclear factor kappa-B (NF-κB, p65) cells at 24 h after reperfusion was observed using an immunofluorescence method. CONCLUSION: Overall, 20-HETE might activate microglia to aggravate RIRI by the NF-κB pathway, but HET0016 has significant protective effects for the retina.

Nanoparticles synergy: Enhancing wheat (Triticum aestivum L.) cadmium tolerance with iron oxide and selenium.

Nanotechnology is capturing great interest worldwide due to their stirring applications in various fields and also individual application of iron oxide nanoparticle (FeO - NPs) and selenium nanoparticles (Se - NPs) have been studied in many literatures. However, the combined application of FeO and Se - NPs is a novel approach and studied in only few studies. For this purpose, a pot experiment was conducted to examine various growth and biochemical parameters in wheat (Triticum aestivum L.) under the toxic concentration of cadmium (Cd) i.e., 50 mg kg-1 which were primed with combined application of two levels of FeO and Se - NPs i.e., 15 and 30 mg L-1 respectively. The results showed that the Cd toxicity in the soil showed a significantly (P < 0.05) declined in the growth, gas exchange attributes, sugars, AsA-GSH cycle, cellular fractionation, proline metabolism in T. aestivum. However, Cd toxicity significantly (P < 0.05) increased oxidative stress biomarkers, enzymatic and non-enzymatic antioxidants including their gene expression in T. aestivum. Although, the application of FeO and Se - NPs showed a significant (P < 0.05) increase in the plant growth and biomass, gas exchange characteristics, enzymatic and non-enzymatic compounds and their gene expression and also decreased the oxidative stress, and Cd uptake. In addition, individual or combined application of FeO and Se - NPs enhanced the cellular fractionation and decreases the proline metabolism and AsA - GSH cycle in T. aestivum. These results open new insights for sustainable agriculture practices and hold immense promise in addressing the pressing challenges of heavy metal contamination in agricultural soils.

Effect of Carbonation Treatment on the Properties of Steel Slag Aggregate.

Steel slag is the waste slag generated after steel smelting, which has cementitious activity. However, untreated steel slag can damage the integrity of steel slag concrete due to its harmful expansion. This study prepared porous aggregates by mixing powdered steel slag, fly ash, and cement and carbonated them with CO2 under high pressure conditions (0.2 MPa). The effect of carbonation on the performance of steel slag aggregate was studied using volume stability and crushing value. The effect of different carbonation conditions on the products was studied using X-ray diffraction (XRD) and thermogravimetric (TG) analyses, and the carbon sequestration efficiency of steel slag under different treatment methods was quantitatively evaluated. The research results indicate that untreated steel slag was almost completely destroyed and lost its strength after autoclave curing. With the increase in temperature and carbonation time, the performance of steel slag aggregate gradually improved and the pulverization rate, expansion rate, and crushing value gradually decreased. According to the experimental results of XRD and TG, it was found that the reaction between f-CaO (free CaO) and CO2 in steel slag generated CaCO3, filling the pores inside the aggregate, which was the internal reason for the improvement of aggregate performance. After comparison, the best carbonation method was maintained at 55 °C for 72 h. After carbonation, the steel slag aggregate had a pulverization rate of 2.4%, an expansion rate of 0.23%, a crushing value of 23%, and a carbon sequestration efficiency of 11.27% per unit weight of aggregate.

Effect of Clindamycin compared with Ampicillin-Sulbactam as prophylactic antibiotics for wound infections following major surgery for head and neck cancer: A meta-analysis.

A meta-analysis examination was implemented to review the effect of Clindamycin compared with Ampicillin-Sulbactam as prophylactic antibiotics (PAs) management for surgical site wound infections (SSWIs) following major surgery (MS) for head and neck cancer (H&NC). A comprehensive literature examination till May 2023 was done and 1296 interrelated examinations were reviewed. The six elected examinations, enclosed 4293 personals with MS for H&NC were in the utilized examinations' starting point, 1722 of them were utilizing Clindamycin, and 2571 were utilizing Ampicillin-Sulbactam. Odds ratio (OR) and 95% confidence intervals (CIs) were utilized to appraise the consequence of Clindamycin compared with Ampicillin-Sulbactam as PAs management for SSWIs following MS for H&NC by the dichotomous approach and a fixed or random model. Clindamycin had significantly higher SSWI compared with Ampicillin-Sulbactam (OR, 2.65; 95% CI, 1.40-5.02, p = 0.003) in personals with MS for H&NC. Clindamycin had significantly higher SSWI compared with Ampicillin-Sulbactam in personals with MS for H&NC. However, caution needs to be taken when interacting with its values because there was a low sample size of some of the chosen examinations and a low number of examinations found for the comparisons in the meta-analysis.

Atypical Carcinoid of the Larynx: A Case Report.

Neuroendocrine carcinomas are a spectrum of rare and highly heterogeneous malignant tumors. Neuroendocrine carcinomas mainly arise from neuroendocrine cells scattered throughout the body. They mainly occur in the lung and gastrointestinal tract. Atypical carcinoid of the larynx is a rare type of neuroendocrine carcinoma, which is easily misdiagnosed as hemangioma in appearance. We mainly feature the disease to you through the diagnosis and treatment of a case of atypical carcinoid of the larynx.

Smoking behavior might affect allergic rhinitis and vasomotor rhinitis differently: A mendelian randomization appraisal.

BACKGROUND: Allergic rhinitis and vasomotor rhinitis are harassing numerous patients and their risk factors have not been well investigated. Here, we try to identify their risk factors and distinguish these 2 diseases. METHODS: A two-sample Mendelian randomization (MR) study was implemented to discover the risk factors of allergic and vasomotor rhinitis. Based on previous studies, we selected 15 potential risk factors and the genome-wide summary statistics were extracted from the non-FinnGen consortium. The genome-wide summary statistics of rhinitis were obtained from the FinnGen consortium. Both univariable MR and multivariable MR analyses were performed to identify the causal risk factors. The Cochrane's Q value was calculated to appraise the heterogeneity. MR-Egger intercept and MR-RPESSO were utilized to appraise the pleiotropy. RESULTS: In the univariable model, the number of cigarettes per day can decrease the risk of allergic rhinitis (IVW OR = 0.29[0.18, 0.47], p-value = 2.70 × 10-7) while increasing the risk of vasomotor rhinitis (IVW OR = 1.30[1.04, 1.62], p-value = 0.022). Besides, no other risk factors could affect the risk of either allergic or vasomotor rhinitis. After adjusting for age of smoking initiation and alcohol intake, the cigarettes per day could still decrease the risk of allergic rhinitis (IVW OR = 4.66 × 10-3 [1.99 × 10-4, 0.11], p-value = 0.003) while not affecting the risk of vasomotor rhinitis (IVW OR = 0.92[0.44, 1.96], p-value = 0.834). CONCLUSION: Smoking can affect the risk of allergic and vasomotor rhinitis differently where it decreases the risk of allergic rhinitis and increases the risk of vasomotor rhinitis.

LncRNA XIST Engages in Psoriasis via Sponging miR-338-5p to Regulate Keratinocyte Proliferation and Inflammation.

INTRODUCTION: Psoriasis is an immune-mediated polygenic inflammatory skin disease in which keratinocyte proliferation is an important mechanism. The study investigated the role and regulatory relationship between lncRNA XIST and miR-338-5p in psoriatic patients and cell models. METHODS: Serum samples were collected from 55 psoriasis patients. HaCaT was recruited for the cell experiments, and induced by M5 cytokines to mimic psoriasis in vitro. XIST and miR-338-5p levels were detected via qRT-PCR. Cell viability under different treatments was evaluated using CCK-8. ELISA was applied to measure the concentration of inflammatory cytokines. The regulatory relationship was confirmed using luciferase reporter gene assay. RESULTS: Serum XIST was elevated in patients with psoriasis and can distinguish the psoriasis patients from healthy controls according to the receiver operating characteristic curve. A high level of XIST was positively correlated with the PASI score and serum tumor necrosis factor-alpha (TNF-α), interleukin-17A [IL-17A], and IL-22 concentrations in psoriasis patients. XIST silencing suppressed M5-induced keratinocyte proliferation and restrained the discharge of inflammatory cytokines (TNF-α, IL-17A, IL-22) and chemokines (CXCL1, CXCL8, CCL20). XIST can sponge miR-338-5p, and miR-338-5p downregulation abolished the inhibitory effect of XIST silencing on cell proliferation and inflammation. miR-338-5p was highly expressed in the clinical serum samples from psoriasis patients. The target relationship between miR-338-5p and IL-6 was proved. CONCLUSION: LncRNA XIST is highly expressed in the serum of patients with psoriasis, and was positively correlated with disease severity and inflammation. XIST may regulate keratinocyte proliferation and inflammation via regulating miR-338-5p/IL-6 axis.

Survival analysis of 8785 malignant lymphoma cases in the oral and nasal cavities in the USA: a cohort study.

OBJECTIVE: To identify the factors associated with the survival of malignant Hodgkin and non-Hodgkin lymphomas in oral and nasal cavities.Study design. Retrospective cohort survival analysis. METHODS: The Surveillance, Epidemiology and End Results 18 database was used to analyse the factors associated with the 5-year survival rate of malignant lymphomas diagnosed in the oral cavity and pharynx (OCP) and nasal cavity and sinus (NCS) regions from 1988 to 2011 for all patients in the USA. Multivariable Cox regression models were used to calculate the HR of malignant lymphoma death overall and by the site of cancer diagnosis. RESULTS: Among the 8785 patients included in the analysis, 4103 (46.7%) were women, 6096 (69.4%) were non-Hispanic (NH) white, 635 (7.2%) were NH black and 1209 (13.8%) were Hispanic patients of all races. We found that a higher 5-year survival rate of malignant lymphoma is associated with: female gender; younger age at diagnosis; NH white race/ethnicity; diagnosis in the oral cavity; receiving surgery/radiation and surgery/radiation, surgery and chemotherapy as the treatment; diagnosis at a localised stage and diagnosis in later calendar years. No association with lymphoma subtype was observed. CONCLUSION: We have identified several demographics and prognosis factors associated with the 5-year survival rate of malignant lymphomas in the OCP and NCS regions. These findings warrant greater public health attention on the prognosis of malignant lymphomas in the OCP and NCS regions among the most vulnerable populations.

High Expression of BCL11A Predicts Poor Prognosis for Childhood MLL-r ALL.

BACKGROUND: Despite much improvement in the treatment for acute lymphoblastic leukemia (ALL), childhood ALLs with MLL-rearrangement (MLL-r) still have inferior dismal prognosis. Thus, defining mechanisms underlying MLL-r ALL maintenance is critical for developing effective therapy. METHODS: GSE13159 and GSE28497 were selected via the Oncomine website. Differentially expressed genes (DEGs) between MLL-r ALLs and normal samples were identified by R software. Next, functional enrichment analysis of these DEGs were carried out by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Set Enrichment Analysis (GSEA), and Search Tool for the Retrieval of Interacting Genes/Proteins (STRING). Then, the key hub genes and modules were identified by Weighted Gene Co-expression Network Analysis (WGCNA). Therapeutically Applicable Research to Generate Effective Treatments (TARGET) ALL (Phase I) of UCSC Xena analysis, qPCR, and Kaplan-Meier analysis were conducted for validating the expression of key hub genes from bone marrow cells of childhood ALL patients or ALL cell lines. RESULTS: A total of 1,045 DEGs were identified from GSE13159 and GSE28497. Through GO, KEGG, GSEA, and STRING analysis, we demonstrated that MLL-r ALLs were upregulating "nucleosome assembly" and "B cell receptor signal pathway" genes or proteins. WGCNA analysis found 18 gene modules using hierarchical clustering between MLL-r ALLs and normal. The Venn diagram was used to filter the 98 hub genes found in the key module with the 1,045 DEGs. We identified 18 hub genes from this process, 9 of which were found to be correlated with MLL-r status, using the UCSC Xena analysis. By using qPCR, we validated these 9 hub key genes to be upregulated in the MLL-r ALLs (RS4;11 and SEM) compared to the non-MLL-r ALL (RCH-ACV) cell lines. Three of these genes, BCL11A, GLT8D1 and NCBP2, were shown to be increased in MLL-r ALL patient bone marrows compared to the non-MLL-r ALL patient. Finally, Kaplan-Meier analysis indicated that childhood ALL patients with high BCL11A expression had significantly poor overall survival. CONCLUSION: These findings suggest that upregulated BCL11A gene expression in childhood ALLs may lead to MLL-r ALL development and BCL11A represents a new potential therapeutic target for childhood MLL-r ALL.

The clinical application of PIVKA-II in hepatocellular carcinoma and chronic liver diseases: A multi-center study in China.

BACKGROUND: Due to the absence of specific symptoms and low survival rate, efficient biomarkers for hepatocellular carcinoma (HCC) diagnosis are urgently required. The purpose of this study was to evaluate the diagnostic performance of protein induced by vitamin K absence or antagonist-II (PIVKA-II) and to determine the optimal cutoff values for HBV infection-related HCC. METHODS: We conducted a cross-sectional, multi-center study in China to ascertain the cutoff value for HCC patients in the context of CHB- and HBV-related cirrhosis. The receiver operating characteristic curve (ROC) and the area under the curve (AUC) were used to evaluate the diagnostic performance of PIVKA-II. RESULTS: This study enrolled 784 subjects and demonstrated that PIVKA-II had a sensitivity of 84.08% and a specificity of 90.43% in diagnosis HCC from chronic liver diseases. PIVKA-II at a cutoff of 37.5 mAU/mL yielded an AUC of 0.9737 (sensitivity 91.78% and specificity 96.30%) in discriminating HCC from chronic hepatitis B (CHB) patients. PIVKA-II at a cutoff of 45 mAU/mL yielded an AUC of 0.9419 (sensitivity 77.46% and specificity 95.12%) in discriminating HCC- from HBV-related cirrhosis patients. Furthermore, using a cutoff value of 40 mAU/mL for PIVKA-II as an HCC marker, only 4.81% (15/312) was positive in chronic hepatitis and 12.80% (37/289) in cirrhosis patients, revealing the satisfactory specificity of PIVKA-II in chronic liver disease of different etiologies. CONCLUSION: Our data indicated that PIVKA-II had satisfactory diagnostic efficiencies and could be used as a screening or surveillance biomarker in HCC high-risk population.

Effects of MgO Expansive Agent and Steel Fiber on Crack Resistance of a Bridge Deck.

To prevent cracks caused by shrinkage of the deck of the Xiaoqing River Bridge, MgO concrete (MC) and steel fiber reinforced MgO concrete (SMC) were used. The deformation and strength of the deck were measured in the field, the resistance to chloride penetration of the concrete was measured in the laboratory, and the pore structure of the concrete was analyzed by a mercury intrusion porosimeter (MIP). The results showed that the expansion caused by the hydration of MgO could suppress the shrinkage of the bridge deck, and the deformation of the deck changed from -88.3 × 10-6 to 24.9 × 10-6, effectively preventing shrinkage cracks. At the same time, due to the restriction of the expansion of MgO by the steel bars, the expansion of the bridge deck in the later stage gradually stabilized, and no harmful expansion was produced. When steel fiber and MgO were used at the same time, the three-dimensional distribution of steel fiber further limited the expansion of MgO. The hydration expansion of MgO in confined space reduced the porosity of concrete, optimized the pore structure, and improved the strength and durability of concrete. The research on the performance of concrete in the in-situ test section showed that MgO and steel fiber were safe for the bridge deck, which not only solved the problem of shrinkage cracking of the bridge deck but also further improved the mechanical properties of the bridge deck.

MiR-519a functions as a tumor suppressor and is negatively associated with poor prognosis of non-small cell lung cancer.

BACKGROUND: Non-small cell lung cancer (NSCLC) is the major type of lung cancer. MicroRNAs (miRNAs) are currently considered as novel targets and tools in cancer therapy. OBJECTIVE: The aim of this study was to investigate the expression level and functional role of miR-519a in NSCLC, as well as its clinical values. METHODS: One hundred and two patients with NSCLC were recruited. Quantitative real-time PCR (qRT-PCR) was used for the measurement of the expression level of miR-519a. Kaplan-Meier survival and Cox regression analyses were conducted to explore the prognostic significance of miR-519a in NSCLC. MTT and Transwell assays were used to detect the effect of miR-519a on NSCLC cell proliferation, migration, and invasion. RESULTS: MiR-519a was significantly downregulated in NSCLC tissues, as well as NSCLC cell lines. The expression level of miR-519a was prominently associated with lymph node metastasis and TNM stage. Kaplan-Meier analysis suggested that low miR-519a expression was closely associated with shorter overall survival. Multivariate Cox regression analysis demonstrated that miR-519a expression level and TNM stage were two independent prognostic factors for 5-year overall survival in NSCLC patients. In vitro study, miR-519a significantly inhibited the proliferation, migration, and invasion of NSCLC cells. STAT3 was proved to be the target gene of miR-519a. CONCLUSIONS: MiR-519a functions as a tumor suppressor and inhibits tumor progression of NSCLC via targeting STAT3. MiR-519a may act as a prognostic biomarker and therapeutic target for NSCLC.

The significance of exosomes in the development and treatment of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the most commonmalignancy. Exsome plays a significant role in the elucidation of signal transduction pathways between hepatoma cells, angiogenesis and early diagnosis of HCC. Exosomes are small vesicular structures that mediate interaction between different types of cells, and contain a variety of components (including DNA, RNA, and proteins). Numerous studies have shown that these substances in exosomes are involved in growth, metastasis and angiogenesis in liver cancer, and then inhibited the growth of liver cancer by blocking the signaling pathway of liver cancer cells. In addition, the exosomal substances could also be used as markers for screening early liver cancer. In this review, we summarized to reveal the significance of exosomes in the occurrence, development, diagnosis and treatment of HCC, which in turn might help us to further elucidate the mechanism of exosomes in HCC, and promote the use of exosomes in the clinical diagnosis and treatment of HCC.

Deformation and Compressive Strength of Steel Fiber Reinforced MgO Concrete.

To reduce the cracking caused by shrinkage and avoid the brittle behavior of concrete, MgO expansion agent and steel fibers were used in this paper. Firstly, the effect of MgO and steel fibers on the compressive strength of concrete was compared. The results showed that the compressive strength of steel fibers reinforced concrete (SC) and steel fiber reinforced MgO concrete (SMC) was significantly improved. Compared with ordinary concrete (OC), SMC's 28 days compressive strength increased by 19.8%. Secondly, the influence of MgO and steel fibers with different contents on the self-volumetric deformation of concrete was compared through the experiment. The results showed that as a result of the hydration expansion of MgO, MC and SMC both showed obvious expansion, and their 190 days expansion was 335 µ ε and 288 µ ε , respectively. Lastly, through a scanning electron microscope (SEM) test, it was found that the constraint effect of steel fibers changed the expansion mode of MgO from outward expansion to inward extrusion, thus improving the interfacial bond strength of concrete.

Underestimated disease prevalence and severe phenotypes in patients with biallelic variants: A cohort study of primary familial brain calcification from China.

BACKGROUND: Primary familial brain calcification (PFBC) is a rare calcifying disorder of the brain with extensive clinical and genetic heterogeneity. Its prevalence is underestimated due to clinical selection bias (compared with symptomatic PFBC patients, asymptomatic ones are less likely to undergo genetic testing). METHODS: A total of 273 PFBC probands were enrolled in a multicenter retrospective cohort study by two different approaches. In Group I (nonsystematic approach), 37 probands diagnosed at our clinic were enrolled. In Group II (systematic approach), 236 probands were enrolled by searching the medical imaging databases of 50 other hospitals using specific keywords. Genetic testing of four genes known to be causative of autosomal dominant PFBC was performed in all probands using cDNA. All identified variants were further confirmed using genomic DNA and classified according to ACMG-AMP recommendations. RESULTS: Thirty-two variants including 22 novel variants were detected in 37 probands. Among these probands, 83.8% (31/37) were asymptomatic. Two probands with homozygous pathogenic SLC20A2 variants presented more severe brain calcification and symptoms. Based on the variant detection rate of probands in Group II, we extrapolated an overall minimal prevalence of PFBC of 6.6 per 1,000, much higher than previously reported (2.1 per 1000). CONCLUSIONS: We identified a higher proportion of genetically confirmed PFBC probands who were asymptomatic. These patients would be overlooked due to clinical selection bias, leading to underestimation of the disease prevalence. Considering that PFBC patients with biallelic variants had more severe phenotypes, this specific condition should be focused on in genetic counseling.

Finite Element Analysis of the Mouse Distal Femur with Tumor Burden in Response to Knee Loading.

Breast cancer-associated bone metastasis induces bone loss, followed by an increased risk of bone fracture. To develop a strategy for preventing tumor growth and protecting bone, an understanding of the mechanical properties of bone under tumor burden is indispensable. Using a mouse model of mammary tumor, we conducted finite element analysis (FEA) of two bone samples from the distal femur. One sample was from a placebo-treated mouse, and the other was from a mouse treated with the investigational drug candidate, PD407824, an inhibitor of checkpoint kinases. Mechanical testing and microCT images revealed that bone strength is improved by administration of PD407824. In response to loading to the knee, FEA predicted that the peaks of von Mises stress, an indicator of fracture yielding, as well as the third principal compressive stress, were higher in the placebo-treated femur than the drug-treated femur. Higher peak stresses in trabecular segments were observed in the lateral condyle, a critical region for integrity of the knee joint. Collectively, this FE study supports the notion that mechanical weakening of the femur was observed in the tumor-invaded trabecular bone, and chemical agents such as PD407824 may potentially assist in preventing bone loss and bone fracture.

Tumor necrosis factor α accelerates Hep-2 cells proliferation by suppressing TRPP2 expression.

TRPP2, a Ca2+-permeable non-selective cation channel, has been shown to negatively regulate cell cycle, but the mechanism underlying this regulation is unknown. Tumor necrosis factor α (TNF-α) is a proinflammatory cytokine extensively involved in immune system regulation, cell proliferation and cell survival. However, the effects and mechanisms for the role of TNF-α in laryngeal cancer remain unclear. Here, we demonstrated using western blot analyses and intracellular Ca2+ concentration measurements that TNF-α treatment suppressed both TRPP2 expression and ATP-induced Ca2+ release in a laryngeal cancer cell line (Hep-2). Knockdown of TRPP2 by a specific siRNA significantly decreased ATP-induced Ca2+ release and abolished the effect of TNF-α on the ATP-induced Ca2+ release. TNF-α treatment also enhanced Hep-2 cell proliferation and growth, as determined using cell counting and flow cytometry cell cycle assays. Moreover, TNF-α treatment down-regulated phosphorylated protein kinase R-like endoplasmic reticulum kinase (p-PERK) and phosphorylated eukaryotic translation initiation factor (p-eIF2α) expression levels, without affecting PERK and eIF2α expression levels in Hep-2 cells. We concluded that suppressing TRPP2 expression and TRPP2-mediated Ca2+ signaling may be one mechanism underlying TNF-α-enhanced Hep-2 cell proliferation. These results offer new insights into the mechanisms of TNF-α-mediated laryngeal cancer cell proliferation, and provide evidences showing a potential role of TNF-α in the development of laryngeal cancer.

Diagnostic performance of tumor markers AFP and PIVKA-II in Chinese hepatocellular carcinoma patients.

Alpha-fetoprotein is an effective biomarker as an aid in hepatocellular carcinoma detection in many countries. However, alpha-fetoprotein has its limitations, especially in early hepatocellular carcinoma diagnosis. Protein induced by vitamin K absence or antagonist-II is another biomarker that is used for hepatocellular carcinoma detection. The aim of this study is to compare the diagnostic performance of alpha-fetoprotein and protein induced by vitamin K absence or antagonist-II alone and in combination to explore improving biomarker performance as an aid in early hepatocellular carcinoma detection. In this study a total of 582 serum samples including 132 hepatocellular carcinoma patients, 250 non-hepatocellular carcinoma patients, and 200 healthy volunteers were collected. Alpha-fetoprotein and protein induced by vitamin K absence or antagonist-II levels were measured by both chemiluminescent enzyme immunoassay on LUMIPULSE platform and by chemiluminescent microparticle immunoassay on ARCHITECT platform. Receiver operation characteristic curve analyses were performed for each biomarker and in combination. The results showed that Alpha-fetoprotein and protein induced by vitamin K absence or antagonist-II in combination have shown higher area under the curve compared to alpha-fetoprotein alone for diagnosis in whole patients (0.906 vs 0.870) in hepatocellular carcinoma early-stage patients (0.809 vs 0.77) and in hepatitis B virus-related hepatocellular carcinoma patients (0.851 vs 0.788) with ARCHITECT platform. Protein induced by vitamin K absence or antagonist-II showed higher area under the curve than alpha-fetoprotein for diagnosis of hepatitis B virus-related hepatocellular carcinoma patients (0.901 vs 0.788).We conclude that Combining alpha-fetoprotein and protein induced by vitamin K absence or antagonist-II may improve the diagnostic value for early detection of hepatocellular carcinoma. Protein induced by vitamin K absence or antagonist-II performs better than alpha-fetoprotein in diagnosis of hepatitis B virus-related hepatocellular carcinoma patients.

Cycling hypoxia affects cell invasion and proliferation through direct regulation of claudin1 / claudin7 expression, and indirect regulation of P18 through claudin7.

Claudins (CLDNs), the major integral membrane proteins at tight junction, play critical roles in apical cell-to-cell adhesion, maintenance of epithelial polarity, and formation of impermeable barriers between epithelial cells.We investigated in this study the expression of CLDNs- Claudin1 (CLDN1) and Claudin7 (CLDN7), and their relation to tumor progression in nasopharyngeal cancer (NPC). CLDN7, rather than CLDN1, showed higher expression in both undifferentiated tumor tissue and the poorly differentiated CNE2 cells, compared with differentiated tissue and the highly differentiated CNE1 cells. Furthermore, knockdown of CLDN7 dramatically inhibited the metastasis and invasion of CNE2 cells suggesting that CLDN7 could act as a biomarker for NPC metastasis.Cycling hypoxia could induce significant changes in CLDN1 and CLDN7 expression in NPC cells. Genetics analysis demonstrated that CLDN1/CLDN7 were not only regulated directly by HIF1a but also affected each other through a feedback mechanism. CLDN7 acted as a bridge to promote HIF1a-induced P18 expression and cell differentiation. Taken together, our results provide evidence that adjusting the oxygenation time and cycles in NPC might be an effective method to prevent / delay the metastasis of poorly differentiated NPC cells.

TRPP2 Enhances Metastasis by Regulating Epithelial-Mesenchymal Transition in Laryngeal Squamous Cell Carcinoma.

BACKGROUND/AIM: Surgery and chemotherapy treatments of human laryngeal squamous cell carcinoma (HLSCC) may fail due to metastasis, in which epithelial-mesenchymal transition (EMT) plays an important role. TRPP2, a nonselective cation channel, is expressed in various cell types and participates in many biological processes. Here, we show that TRPP2 enhanced metastasis by regulating EMT. METHODS: We used immunohistochemistry, western blotting, Ca2+ imaging, transwell and wound healing assays to investigate TRPP2 expression levels in HLSCC tissue, and the role of TRPP2 in invasion and metastasis of a human laryngocarcinoma cell line (Hep2 cell). RESULTS: We found that TRPP2 protein expression levels were significantly increased in HLSCC tissue; higher TRPP2 levels were associated with decreased patient survival time and degree of differentiation and advanced clinical stage. Knockdown of TRPP2 by transfection with TRPP2 siRNA markedly suppressed ATP-induced Ca2+ release, wound healing, and cell invasion in Hep2 cells. Moreover, TRPP2 siRNA significantly decreased vimentin expression but increased E-cadherin expression in Hep2 cells. In the EMT signalling pathway, TRPP2 siRNA significantly decreased Smad4, STAT3, SNAIL, SLUG and TWIST expression in Hep2 cells. CONCLUSION: We revealed a previously unknown function of TRPP2 in cancer development and a TRPP2-dependent mechanism underlying laryngocarcinoma cell invasion and metastasis. Our results suggest that TRPP2 may be used as a biomarker for evaluating patient prognosis and as a novel therapeutic target in HLSCC.