Hepatocellular carcinoma (HCC), one of the most prevalent types of cancer worldwide, has an exceedingly poor prognosis. Tandem C2 domain nuclear protein (TC2N) has been implicated in tumorigenesis ...and serves as an oncogene or tumor suppressor in different types of cancer. Here, we explore the possible regulatory activities and molecular mechanisms of TC2N in HCC progression. However, TC2N expression was significantly upregulated in HCC tissues and hepatoma cell lines, and this upregulation was positively correlated with tumor progression in HCC patients. The ectopic overexpression of TC2N accelerated the proliferation, migration, and invasion of HCC cells, whereas its knockdown showed the opposite effects. Bioinformatics analysis showed that TC2N participates in the regulation of the Wnt/β-catenin signaling pathway. Mechanistically, TC2N activated the Wnt/β-catenin signaling pathway by regulating the expression levels of β-catenin and its downstream targets CyclinD1, MMP7, c-Myc, c-Jun, AXIN2, and glutamine synthase. Furthermore, the deletion of β-catenin effectively neutralized the regulation of TC2N in HCC proliferation and metastasis. Overall, this study showed that TC2N promotes HCC proliferation and metastasis by activating the Wnt/β-catenin signaling pathway, indicating that TC2N might be a potential molecular target for the treatment of HCC.
Based on the Beijing Eye Study 2011, a detailed ophthalmic examination was performed including spectral-domain optical coherence tomography (SD-OCT) with enhanced depth imaging for measurement of ...subfoveal choroidal thickness (SFCT) and relative height of posterior scleral staphyloma. OCT images were obtained in 103 highly myopic eyes (≤-6.00 diopters) and 227 normal eyes. The mean SFCT in highly myopic eyes was 110.6 ± 85.2 μm (range, 3 to 395 μm). The SFCT of high myopia without posterior scleral staphyloma(55 eyes) was 157.79 ± 85.18 μm, which was significantly greater than that (54.94 ± 49.96 μm) of high myopia with posterior scleral staphyloma (48 eyes) (P < 0.001). In multivariate analysis, posterior scleral staphyloma was the most important factor of choroidal thinning in high myopia (F = 22.63; P < 0.001), then age (F = 19.14; P < 0.001), axial length (F = 17.37; P < 0.001) and gender (F = 17.31; P < 0.001). The SFCT in highly myopic eyes is very thin and undergoes further thinning with increasing age and axial length (refractive error). Posterior staphyloma formation was a key factor in choroidal thinning in highly myopic eyes and to be a good indicator for risk management of choroidal thinning. Abnormalities of the choroid may play a role in the pathogenesis of myopic degeneration.
A series of 4-substituted fluoronucleosides have been synthesized in order to address the toxicity issue of the parent compound 7, and after in vitro evaluation, the cyclopropylamino analog 1f was ...selected for in vivo study. In mice, this compound exhibited a significantly improved toxicity profile. Administered orally, compound 1f was well-tolerated at a dose up to 3 g/kg and showed insignificant toxicity on white blood cells and a low mutagenic effect at dosages up to 80 mg/kg (single) or 20 mg/kg/day (5 days). In duck HBV (DHBV)-infected duck models, both the serum and liver DHBV DNA levels (74.2 and 82.1%, respectively) were markedly reduced by the treatment of 1f at a dose of 1 mg/kg/day for 10 days. In addition, both the viral DNA levels had a lower degree of recovery after withdrawal of the test compound for 3 days.
The comprehensive understanding of mechanisms involved in the tumor metastasis is urgently needed for discovering novel metastasis-related genes for developing effective diagnoses and treatments for ...lung cancer.
FAM198B was identified from an isogenic lung cancer metastasis cell model by microarray analysis. To investigate the clinical relevance of FAM198B, the FAM198B expression of 95 Taiwan lung adenocarcinoma patients was analyzed by quantitative real-time PCR and correlated to patients' survivals. The impact of FAM198B on cell invasion, metastasis, and tumor growth was examined by
cellular assays and
mouse models. In addition, the N-glycosylation-defective FAM198B mutants generated by site-directed mutagenesis were used to study protein stability and subcellular localization of FAM198B. Finally, the microarray and pathway analyses were used to elucidate the underlying mechanisms of FAM198B-mediated tumor suppression.
We found that the high expression of FAM198B was associated with favorable survival in Taiwan lung adenocarcinoma patients and in a lung cancer public database. Enforced expression of FAM198B inhibited cell invasion, migration, mobility, proliferation, and anchorage-independent growth, and FAM198B silencing exhibited opposite activities
FAM198B also attenuated tumor growth and metastasis
We further identified MMP-1 as a critical downstream target of FAM198B. The FAM198B-mediated MMP-1 downregulation was via inhibition of the phosphorylation of ERK. Interestingly deglycosylation nearly eliminated the metastasis suppression activity of FAM198B due to a decrease of protein stability.
Our results implicate FAM198B as a potential tumor suppressor and to be a prognostic marker in lung adenocarcinoma.
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As an important epigenetic regulator, histone lysine specific demethylase 1 (LSD1) has become an attractive target for the discovery of anticancer agents. In this work, a series of ...tranylcypromine-based derivatives were designed and synthesized. Among them, compound 12u exhibited the most potent inhibitory potency on LSD1 (IC50 = 25.3 nM), and also displayed good antiproliferative effects on MGC-803, KYSE450 and HCT-116 cells with IC50 values of 14.3, 22.8 and 16.3 μM, respectively. Further studies revealed that compound 12u could directly act on LSD1 and inhibit LSD1 in MGC-803 cells, thereby significantly increasing the expression levels of mono-/bi-methylation of H3K4 and H3K9. In addition, compound 12u could induce apoptosis and differentiation, inhibit migration and cell stemness in MGC-803 cells. All these findings suggested that compound 12u was an active tranylcypromine-based derivative as a LSD1 inhibitor that inhibited gastric cancer.
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•Novel tranylcypromine-based derivatives were designed and synthesized.•Compound 12u showed low nanomolar IC50 value against LSD1 and high selectivity for MAO-A and MAO-B.•Compound 12u suppressed LSD1 and induced the accumulation of H3K4 Me1/2 and H3K9 Me2/3.•Compound 12u induced apoptosis and differentiation, and inhibited migration and cell stemness.
This study aims to investigate the value and determine the accuracy of spleen stiffness in predicting the degree of esophageal varices and bleeding in patients with liver cirrhosis.The age, gender, ...liver stiffness, spleen stiffness, and gastroscopy results of 124 inpatients or outpatients with liver cirrhosis and healthy volunteers, who underwent both gastroscopy and FibroScan testing in the fasting state, were retrospectively analyzed. According to the gastroscopy results, the patients and healthy volunteers were divided into six groups: varicose bleeding, severe varices, moderate varices, mild varices, no varices, and healthy control group. Then, the receiver operating characteristic curves were drawn, and the corresponding area under each curve was calculated and evaluated to predict the severity of varices based on the relevance of the area and its parameters.The area under the receiver operating characteristic curve of liver stiffness and spleen stiffness for predicting severe and moderate varices in the bleeding group was 0.955 and 0.989, respectively. The cut-off values were 29.6 kPa and 45.5 kPa, respectively. The area under the receiver operating characteristic curve of liver stiffness for predicting varicose bleeding was 0.860 (95% CI: 0.789-0.931). The liver stiffness cut-off value for predicting varicose bleeding was 33.2 kPa, with a specificity and sensitivity of 66.02% and 95.24%, respectively. The area under the receiver operating characteristic curve of spleen stiffness for predicting varicose bleeding was 0.923 (95% CI: 0.875-0.971). A spleen stiffness cut-off value of 55.2 kPa had a sensitivity and specificity of 90.48% and 86.41%, respectively.Spleen stiffness can predict the degree of esophageal varices and bleeding in liver cirrhosis patients, and has good predictive accuracy.
Alloyed bismuth oxyhalides have been widely used in photocatalytic water treatment processes due to their superior photocatalytic activity. However, there is no report on the removal of NO3− for ...alloyed bismuth oxyhalides, and the mechanism of the effect of alloying on NO3− reduction activity is still unclear. In this work, we prepared a series of BiOClnBr1‐n (0≤n≤1) with different Cl/Br ratios but with controlled similar morphologies, and explored their catalytic activities on reducing NO3− under visible light irradiation. Density functional theory investigations revealed that the formation energy for an oxygen (O) vacancy on the surface of BiOClnBr1‐n alloys is clearly reduced in comparison with the monohalide, illustrating that more O vacancies can be produced on the surface of BiOClnBr1‐n alloys. A high concentration of O vacancies not only promotes the adsorption of NO3− but also enhances the separation efficiency of the photogenerated electron‐hole (e–h) pairs, with both being beneficial to enhance the photocatalytic activity of BiOClnBr1‐n alloys for NO3− reduction. These new discoveries not only promote the design and development of new photocatalysts with excellent NO3− reduction properties, but also help to understand the relationship between alloying effects and semiconductor photocatalytic properties.
Room to manoeuvre: A series of BiOClnBr1‐n (0≤n≤1) nanosheets with different Cl/Br ratios were prepared. It was confirmed that the alloying effect could reduce the formation energy of O vacancies on the surface of BiOClnBr1‐n alloys. O vacancy formation not only promotes the adsorption of NO3−, but also improves the separation ability of photogenerated electron‐hole pairs, both of which being beneficial to enhance the photocatalytic activity of BiOClnBr1‐n alloys for NO3− reduction.
The magnetite (Fe3O4) nanoparticles with different magnetic properties were prepared by coprecipitation of Fe3+ and Fe2+ with an aqueous NaOH solution. The inductive heating property of Fe3O4 ...nanoparticles in an alternating current (ac) magnetic field was investigated. The potential of Fe3O4 nanoparticles was evaluated for localized hyperthermia treatment of cancers. The maximum saturation magnetization Ms of Fe3O4 nanoparticles was 65.53 emu g-1, which was synthesized under the condition of Fe3+/Fe2+ molar ratio at 1.8:1. The Ms of Fe3O4 nanoparticles decreased, while the coercivity Hc increased with the increase of Fe3+/Fe2+ molar ratio. Exposed in the ac magnetic field for 29 min, the temperatures of physiological saline suspensions containing different Fe3O4 nanoparticles are 42-97.5 deg C. The inductive heating property of Fe3O4 nanoparticles in the ac magnetic field decreased as Hc increased, while increased with the increase of Ms. The Fe3O4 nanoparticles will be useful as good thermoseeds for localized hyperthermia treatment of cancers.
Sensitive information: Hydrogen bonds stabilize protein structures and are critical for many chemical and biological phenomena. NMR studies found that the one‐bond 1H–15N scalar coupling constant is ...increased by up to 1.6 Hz when a hydrogen bond is formed. These coupling constants therefore provide a sensitive tool for studying protein structure.
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