Effects of microwave ablation on serum Golgi protein 73 in patients with primary liver cancer.

BACKGROUND: Microwave ablation (MWA) is an effective treatment option for patients with primary liver cancer. However, it has been reported that the MWA procedure induces a hepatic inflammatory response and injury, which may negatively affect the efficacy of MWA. As such, the discovery of reliable markers to monitor the patient's response to MWA is needed. Golgi protein 73 (GP73) has been shown to be associated with chronic liver disease. To date, the potential value of serum GP73 in the dynamic monitoring during MWA of liver cancer remains unclear. AIM: To examine the effects of MWA on the serum levels of GP73 in patients with primary liver cancer. METHODS: A total of 150 primary liver cancer patients with a single small lesion (≤ 3 cm in diameter) were retrospectively enrolled spanning the period between January 2016 and October 2018. All of the patients received MWA for the treatment of primary liver cancer. Serum GP73, alpha-fetoprotein (AFP), and widely used liver biochemical indicators [serum albumin, total bilirubin (TBIL), alanine aminotransferase (ALT), and aspartate aminotransferase (AST)] were compared before MWA and at different time points, including 1, 2, and 4 wk following the ablation procedure. RESULTS: Complete tumor ablation was achieved in 95.33% of the patients at 1 mo after MWA. The 1-, 2-, and 3-year disease-free survival rates were 74.67%, 59.33%, and 54.00%, respectively. The serum AFP levels were significantly decreased at 1, 2, and 4 wk after MWA; they returned to the normal range at 12 wk after MWA; and they remained stable thereafter during follow-up in those cases without recurrence. In contrast, the serum GP73 levels were significantly increased at 1 and 2 wk after MWA. The serum GP73 levels reached the peak at 2 wk after MWA, started to decline after hepatoprotective treatment with glycyrrhizin and reduced glutathione, and returned to the pretreatment levels at 12 and 24 wk after MWA. Notably, the changes of serum GP73 in response to MWA were similar to those of TBIL, ALT, and AST. CONCLUSION: Serum GP73 is markedly increased in response to MWA of liver cancer. Thus, serum GP73 holds potential as a marker to monitor MWA-induced inflammatory liver injury in need of amelioration.

RhIII-Catalyzed Direct Heteroarylation of C(sp3)-H and C(sp2)-H Bonds in Heterocycles with N-Heteroaromatic Boronates.

Herein, we disclose a RhIII-catalyzed heteroarylation of C(sp3)-H and C(sp2)-H bonds in heterocycles with organoboron reagents. This protocol displays high efficiency and excellent functional group tolerance. A range of heterocyclic boronates with strong coordinating atoms, including pyridine, pyrimidine, pyrazole, thiophene, and furan derivatives, can be extensively served as the coupling reagents. The direct heteroarylation method could supply potential application in terms of the synthesis of drug molecules with multiple heterocycles.

RhIII-Catalyzed C-H (Het)arylation/Vinylation of N-2,6-Difluoroaryl Acrylamides.

RhIII-catalyzed sp2 C-H cross-coupling of acrylamides with organoboron reactants has been accomplished using a commercially available N-2,6-difluoroaryl acrylamide auxiliary. A broad range of aryl and vinyl boronates as well as a variety of heterocyclic boronates with strong coordinating ability can serve as the coupling partners. This transformation proceeds under moderate reaction conditions with excellent functional group tolerance and high regioselectivity.

Mitochondria-targeted near-infrared fluorescent probe for the detection of carbon monoxide in vivo.

Carbon monoxide is a critical gasotransmitter in the body and related with mitochondrial respiration. To date, various fluorescent probes for CO have been well proposed, but two main problems remain. One is that most of the probes are not mitochondria-targeting, even if the probes claim to be able to detect CO in living cells. The other is that the probes for CO display excitation and emission within the ultraviolet or visible range, which hinders their applications in vivo. Herein, a hemicyanine-based near-infrared (NIR) fluorescent probe named CyAPC is first synthesized and used to detect mitochondrial CO. The characteristics of probe CyAPC are as follows: (1) The fluorescence emission of the sensing system is at 736 nm belonging to NIR region, which is suitable for bioimaging in vivo. (2) CyAPC, a positively charged molecule, would have a high tendency to localize in mitochondria of cells. (3) The fluorescence change of the probe is attributed to the fact that CO with Pd2+ induced cleavage of the allyl formate group from the probe and CyAPC (fluorescence off) is transformed into CyOH (fluorescence on), which is proved by HPLC, MS and DFT calculation. (4) The NIR fluorescent probe is applied for the detection of exogenous and endogenous CO in various biological samples such as cell, tissue and in vivo with satisfactory results.

A Dual-Response Fluorescent Probe for the Detection of Viscosity and H2S and Its Application in Studying Their Cross-Talk Influence in Mitochondria.

Intracellular viscosity is an essential microenvironmental parameter and H2S is a critical gaseous signaling molecule, which are both related to various physiological processes. It is reported that the change of viscosity and an imbalance of H2S production in the mitochondria are both associated with overexpression of amyloid betapeptide (Aß), which is thought to play a central role in the pathogenesis of Alzheimer's disease (AD). However, to our best knowledge, no fluorescent probe is found for dual detection of mitochondrial viscosity and H2S. Herein, a dual-response fluorescent probe (Mito-VS) is designed and synthesized to monitor the level of viscosity and H2S, respectively. Mito-VS itself is nonfluorescent due to a free intramolecular rotation between dimethylaniline and pyridine. After the increase of viscosity, the rotation is prohibited and an intense red fluorescence is released. Upon the addition of H2S, the probe can react with H2S to form compound 3 and a strong green fluorescence can be observed. Moreover, the probe possesses a good mitochondrion-targeting ability and is applied for imaging the change of viscosity on the red channel and visualizing the variation of exogenous and endogenous H2S concentration on the green channel in mitochondria. Most importantly, the probe is capable of studying the cross-talk influence of viscosity and H2S in mitochondria, which is very beneficial for knowing the pathogenesis of AD.

Detecting and Imaging of γ-Glutamytranspeptidase Activity in Serum, Live Cells, and Pathological Tissues with a High Signal-Stability Probe by Releasing a Precipitating Fluorochrome.

γ-Glutamytranspeptidase (GGT) is a significant tumor-related biomarker that overexpresses in several tumor cells. Accurate detection and imaging of GGT activity in serum, live cells, and pathological tissues hold great significance for cancer diagnosis, treatment, and management. Recently developed small molecule fluorescent probes for GGT tend to diffuse to the whole cytoplasm and then translocate out of live cells after enzymatic reaction, which make them fail to provide high spatial resolution and long-term imaging in biological systems. To address these problems, a novel fluorescent probe (HPQ-PDG) which releases a precipitating fluorochrome upon the catalysis of GGT is designed and synthesized. HPQ-PDG is able to detect GGT activity with high spatial resolution and good signal-stability. The large Stokes shift of the probe enables it to detect the activity of GGT in serum samples with high sensitivity. To our delight, the probe is used for imaging GGT activity in live cells with the ability of discriminating cancer cells from normal cells. What's more, we successfully apply it for pathological tissues imaging, with the results indicating that the potential application of HPQ-PDG in histopathological examination. All these results demonstrate the potential application of HPQ-PDG in the clinic.

A near-infrared fluorescent probe based on BODIPY derivative with high quantum yield for selective detection of exogenous and endogenous cysteine in biological samples.

Cysteine (Cys) is involved in cellular growth and Cys deficiency is related with many diseases. So far, a number of fluorescent probes have been constructed for the detection of Cys successfully. However, the probes are difficult to discriminate Cys from Hcy and the emission wavelength of the probes is in ultraviolet or visible range. Herein, a NIR fluorescent probe named NIR-BODIPY-Ac is synthesized and used to detect Cys. The emission wavelength of the probe is at 708 nm that belongs to near-infrared (NIR) region by attaching indolium to BODIPY core, which is suitable for bioimaging in vivo. Moreover, the probe exhibits high fluorescence quantum yield (Φ = 0.51) after the addition of Cys and high sensitivity toward Cys with 81-fold fluorescence enhancement. The linear range of the probe for Cys covers from 0.2 to 30 µM with a detection limit of 0.05 µM. Furthermore, the probe shows high selectivity towards Cys owing to the fact that there is more fast reaction rate between the probe and Cys than that of Hcy. In particular, the NIR fluorescent probe is applied for the detection of exogenous and endogenous Cys in biological samples such as cell, tissue and mouse with satisfactory results.

Facile and Sensitive Near-Infrared Fluorescence Probe for the Detection of Endogenous Alkaline Phosphatase Activity In Vivo.

Alkaline phosphatase (ALP) is an essential enzyme and widely distributes in a variety of tissues. To date, various nanomaterial and small-molecule fluorescent probes for ALP have been constructed successfully, but the emission wavelengths of these probes are in the ultraviolet or visible range, which is not beneficial for bioimaging. Herein, a hemicyanine-based near-infrared (NIR) fluorescent probe named CyP is first synthesized and used to detect ALP activity. The characteristics of probe CyP are as follows: (1) The probe possesses a facile structure, which can be obtained by easy synthetic steps. (2) The fluorescence emission of the sensing system is at 738 nm belonging to NIR region, which is suitable for bioimaging in vivo. (3) The probe exhibits high sensitivity to ALP with 10-fold fluorescence enhancement and low detection limit (0.003 U/mL) can match the level of ALP in vivo. (4) The fluorescent change of the probe is attributed to the fact that ALP-catalyzed cleavage of the phosphate group in CyP induces the transformation of CyP (fluorescence off) into CyOH (fluorescence on), which is proved by HPLC, 31P NMR, MS, and DFT calculation. (5) The NIR fluorescent probe is applied for the detection of endogenous ALP activity in various biological samples such as cell, tissue, and living animal with satisfactory results.

Real-Time Monitoring ATP in Mitochondrion of Living Cells: A Specific Fluorescent Probe for ATP by Dual Recognition Sites.

Adenosine triphosphate (ATP) is mainly produced in the mitochondrion and used as a universal energy source for various cellular events. Various fluorescent probes for ATP have been established successfully, but most of them are not appropriate for monitoring the fluctuation of the mitochondrial ATP level. Herein, a fluorescent probe named Mito-Rh is first synthesized and used to recognize ATP in mitochondrion. In the probe, rhodamine, diethylenetriamine, and triphenylphosphonium are selected as fluorophore, reaction site, and mitochondrion-targeting group, respectively. Probe Mito-Rh shows high sensitivity to ATP with 81-fold fluorescence enhancement, and the detection range (0.1-10 mM) can match the concentration level of ATP in the mitochondrion. Moreover, Mito-Rh provides excellent selectivity toward ATP over other biological anions (ADP, AMP, GTP, CTP, UTP) owing to a concurrent effect of dual recognition sites (hydrogen bond and π-π stacking). In particular, the probe can localize in mitochondrion specifically and demonstrates utility in the real-time detection of mitochondrial ATP concentration changes.

Near-Infrared Fluorescent Probe with High Quantum Yield and Its Application in the Selective Detection of Glutathione in Living Cells and Tissues.

Glutathione (GSH), cysteine (Cys), and homocysteine (Hcy) are small-molecular biothiols that play key roles in various biological systems. Among these biothiols, GSH is the most abundant intracellular thiol. Until now, a small number of the near-infrared (NIR) fluorescent probes have been designed for the detection of GSH. Unfortunately, most of these NIR probes are based on cyanine dyes, which generally suffer low fluorescence quantum yield (Φ < 0.25), which are not suitable for bioimaging. In addition, some probes are difficult to effectively distinguish GSH from Cys and Hcy. In this work, an NIR fluorescent probe with high fluorescence quantum yield is developed by introducing a rigid coplanar structure such as rhodamine dyes, and the NIR probe (CyR) with spirolactam structure is first synthesized and used to recognize GSH. The characteristics of this NIR probe are as follows: (1) probe CyR exhibits high fluorescence quantum yield (Φ = 0.43) after the addition of GSH and high sensitivity toward GSH with 75-fold fluorescence enhancement. (2) The probe is highly selective, which will not interfere with the other biological thiols (Cys, Hcy) and amino acids. (3) A possible reaction mechanism of the NIR probe CyR and GSH (Cys, Hcy) can be proposed and proved by 1H NMR, 13C NMR, and MS (mass spectra). (4) The NIR probe displays selective detection of GSH in biological samples such as living cells and tissues.

Rhodamine-based chemodosimeter for fluorescent determination of Hg(2+) in 100% aqueous solution and in living cells.

A rhodamine spirolactam derivative (1) bearing a hydrophilic carboxylic acid group is developed as a fluorescent chemodosimeter for bivalent mercury ions (Hg(2+)) in 100% aqueous solution. It exhibits a highly sensitive "turn-on" fluorescent response toward Hg(2+) with a 42-fold fluorescence intensity enhancement under 1 equiv. of Hg(2+) added. The chemodosimeter can be applied to the quantification of Hg(2+) with a linear range covering from 3.0 × 10(-7) to 1.0 × 10(-5) M and a detection limit of 9.7 × 10(-8) M. Most importantly, the fluorescence changes of the chemodosimeter are remarkably specific for Hg(2+) in the presence of other metal ions, which meet the selective requirements for practical application. Moreover, the experiment results show that the response behavior of 1 towards Hg(2+) is pH independent in neutral condition (pH 5.0-8.0) and the response is fast (response time less than 3 min). Furthermore, the ring-opening mechanism of the rhodamine spirolactam induced by Hg(2+) was supported by NMR, MS, and DFT theoretical calculations. In addition, the proposed chemodosimeter has been used to detect Hg(2+) in water samples and image Hg(2+) in living cells with satisfying results.

A highly sensitive and selective fluorescent probe for trivalent aluminum ion based on rhodamine derivative in living cells.

A rhodamine spirolactam derivative (1) is developed as a colormetric and fluorescent probe for trivalent aluminum ions (Al(3+)). It exhibits a highly sensitive "turn-on" fluorescent response toward Al(3+) with a 70-fold fluorescence intensity enhancement under 2 equiv. of Al(3+) added. The probe can be applied to the quantification of Al(3+) with a linear range covering from 5.0 × 10(-7) to 2.0 × 10(-5) M and a detection limit of 4.0 × 10(-8) M. Most importantly, the fluorescence changes of the probe are remarkably specific for Al(3+) in the presence of other metal ions, which meet the selective requirements for practical application. Moreover, the experiment results show that the response behavior of 1 towards Al(3+) is pH independent in neutral condition (pH 6.0-8.0) and the response of the probe is fast (response time less than 3 min). In addition, the proposed probe has been used to detect Al(3+) in water samples and image Al(3+) in living cells with satisfying results.

A ratiometric fluorescent probe with unexpected high selectivity for ATP and its application in cell imaging.

Naphthalimide-rhodamine compound (NR) is developed as a ratiometric fluorescent probe for ATP detection based on the FRET mechanism. It shows an unexpected high selectivity for ATP over other anions, especially organic phosphate anions, due to simultaneous interactions of two recognition sites, which benefits fluorescence imaging in living cells.

Synergistic increase of oxidative stress and tumor markers in PAH-exposed workers.

In this study, we investigated oxidative stress and tumor marker levels of polycyclic aromatic hydrocarbons (PAHs) in 136 coke oven workers and in 60 control subjects, and evaluated the correlation between oxidative stress and tumor marker levels. Questionnaires on basic demographic information were also administered. Significant differences in employment time and percentages of alcohol drinkers were observed between the control and exposed groups. PAH exposure was assessed using urinary 1-hydroxy-pyrene (1-OHP) levels and was found to be significantly higher in workers than in the controls. Significant differences (P<0.001) of MDA, GST, LDH, NSE, Cyfra21-1, and of SCC and TNF-a (P<0.0001 and P<0.05, P<0.001, respectively) levels were observed among controls and coke-oven workers, except for bottom coke oven workers. Associations between age and risk of increased TNF-a, smoking and increased GST activities, and drinking with increased MDA concentrations, were marginal (P=0.055, P=0.048, P=0.057, respectively). The association between smoking with MDA (P=0.004), NSE (P=0.005), SCC (P=0.004) and TNF-a (P<0.001), and drinking with TNF-a levels was significant (P=0.012). In addition, a significant positive correlation between oxidative stress and tumor markers was found in the present study. These results suggest that a synergistic increase of oxidative stress and tumor markers induced by PAHs may play a role in toxic responses for PAHs in coke oven workers.

The methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and tumor risk: evidence from 134 case-control studies.

Methylenetetrahydrofolate reductase (MTHFR) is an important enzyme involved in folate metabolism, which is essential for DNA synthesis and methylation. Genetic variations in the MTHFR gene seem to contribute to a decreased activity of MTHFR, ultimately confer increased susceptibility to cancer. As the most extensively studied polymorphism, MTHFR C677T polymorphism was shown to contribute to cancer susceptibility but the results were inconsistent. The authors performed a meta-analysis including 134 studies (46,207 cases and 69,160 controls) to address the issue. Odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were used to assess the association. Overall, a significant elevated risk of cancer was associated with the MTHFR C677T polymorphism in T-allele versus C-allele comparison (OR = 1.06, 95% CI 1.02-1.11, P(heterogeneity) < 0.001), homozygote model (OR = 1.08, 95% CI 1.01-1.17, P(heterogeneity) < 0.001) and dominant model (OR = 1.05, 95% CI 1.00-1.10, P(heterogeneity) < 0.001). In the stratified analyses, significantly increased cancer risks were indicated among Asians in all genetic models except for heterozygote model. Further analysis revealed that C677T was significantly associated with an increased risk of esophageal and stomach cancer. This meta-analysis supports an association between the MTHFR C677T polymorphism and increased risk of esophageal and stomach cancer, especially among Asians. Additionally, more high-quality studies and that the covariates responsible for heterogeneity should be controlled to obtain a more conclusive response about the function of MTHFR C677T in cancer.

Ratiometric near-infrared chemosensor for trivalent chromium ion based on tricarboyanine in living cells.

A tricarboyanine derivative (IRPP) is applied as a ratiometric near-infrared chemosensor for detecting trivalent chromium ions (Cr(3+)) in living cells. Upon the addition of Cr(3+) to a solution of IRPP, large-scale shifts in the emission spectrum (from 755 nm to 561 nm) are observed. In the newly developed sensing system, these well-resolved emission peaks yield a sensing system that covers a linear range from 1.0×10(-7) to 1.0×10(-5) M with a detection limit of 2.5×10(-8) M. The experimental results show the response behavior of IRPP towards Cr(3+) is pH independent under neutral conditions (6.0-7.5). Most importantly, the fast response time (less than 3 min) and selectivity for Cr(3+) over other common metal ions provide a strong argument for the use of this sensor in real world applications. As a proof of concept, the proposed chemosensor has been used to detect and quantify Cr(3+) in river water samples and to image Cr(3+) in living cells with encouraging results.

Detection and removal of Hg2+ based on mesoporous silica material functionalized by naphthalimide in aqueous solution.

An inorganic-organic silica material (SBA-15-1), prepared by immobilization of the naphthalimide derivative within the channels of the mesoporous silica material SBA-15, is characterized by several spectroscopic methods. SBA-15-1 can be used as a chemical sensor for detecting and removing Hg(2+) in a heterogeneous system. The fluorescence enhancement of SBA-15-1 was attributed to the formation of a complex between SBA-15-1 and Hg(2+) by a 1:1 complex ratio with the photo-induced electron transfer (PET) being forbidden. The sensor can be applied to the quantification of Hg(2+) with a linear range covering from 1.0 × 10(-7) to 1.0 × 10(-5) M under the neutral condition. Most importantly, the fluorescence changes of the sensor are remarkably specific for Hg(2+) in the presence of other metal ions. Moreover, the response of the sensor toward Hg(2+) is fast and chemically reversible. In addition, the sensor has been used for the determination of Hg(2+) in environmental samples with satisfactory results.

A fluorescent chemosensor for Hg2+ based on a rhodamine derivative in an aqueous solution.

In this paper, we unveil a novel rhodamine compound-based fluorescent chemosensor (compound 1) for fluorescent detection of Hg(2+) in an aqueous solution. The fluorescence enhancement of compound 1 was attributed to the formation of a complex between compound 1 and Hg(2+) by 1:1 complex ration (K = 8.0 × 10(4)), which has been utilized as the basis of fabrication of the Hg(2+)-sensitive chemosensor. A comparison of this method with some other fluorescence methods for the determination of Hg(2+) indicated that this method has high selectivity and good water solubility. The analytical performance characteristics of the proposed Hg(2+)-sensitive chemosensor were investigated. The chemosensor can be applied to the quantification of Hg(2+) with a linear range from 6.6 × 10(-7) to 2.4 × 10(-4) M and a detection limit of 1.3 × 10(-7) M. The experiment results show that the response behavior of compound 1 towards Hg(2+) is pH independent in neutral conditions (pH 5.0-9.0). Most importantly, the fluorescence changes of the chemosensor are remarkably specific for Hg(2+) in the presence of other metal ions, which meet the selective requirements for practical application. Moreover, the response of the chemosensor toward Hg(2+) is fast (response time less than 1 min). In addition, the chemosensor has been used for the determination of Hg(2+) in river water samples with satisfactory results.

A colormetric and fluorescent chemosensor for adenosine-5'-triphosphate based on rhodamine derivative.

A rhodamine spirolactam derivative (1) was developed as a colormetric and fluorescent chemosensor for adenosine-5'-triphosphate (ATP) via hydrogen bonds interaction. As far as we know, this is the first case to explore ATP-induced ring-opening of spirolactam in rhodamine derivatives. It exhibited a highly sensitive "turn-on" fluorescent response toward ATP with a 47-fold fluorescence intensity enhancement under 20 equiv. of ATP added. The chemosensor can be applied to the quantification of ATP with a linear range covering from 1.0×10(-7) to 2.0×10(-4) M and a detection limit of 2.5×10(-8) M. The experiment results show that the response behavior of 1 toward ATP is pH independent in medium condition (pH 6.0-8.0). Most importantly, the novel chemosensor has well solved the problem of serious interferences from other nucleoside polyphosphates such as ADP and AMP generally met by previously reported typical fluorescent chemosensors for ATP. Moreover, the response of the chemosensor toward ATP is fast (response time less than 3 min). In addition, the chemosensor can be used for the fluorescence assay for protein kinase activity with satisfactory results. The chemosensor for ATP based on hydrogen bonds interaction provided a novel strategy for the design of colormetric and ratiometric fluorescent probes for other target anions with high sensitivity and selectivity.

Colorimetric and fluorescent chemosensor for citrate based on a rhodamine and Pb2+ complex in aqueous solution.

In this paper we unveil a novel rhodamine compound based fluorescent chemosensor (1-Pb(2+)) for colormetric and fluorescent detection of citrate in aqueous solution. This is the first fluorescent chemosensor for citrate based on rhodamine compound. The comparison of this method with some other fluorescence methods for citrate indicates that the method can detect citrate in aqueous solution by both color changes and fluorescent changes with long emission wavelength. In the new developed sensing system, 1-Pb(2+) is fluorescent due to Pb(2+)-induced fluorescence enhancement of 1. However, the addition of citrate may release 1 into the solution with quenching of fluorescence. The chemosensor can be applied to the quantification of citrate with a linear range covering from 1.0×10(-7) to 5.0×10(-5) M and a detection limit of 2.5×10(-8) M. The experiment results show that the response behavior of 1-Pb(2+) towards citrate is pH independent in medium condition (pH 6.0-8.0). Most importantly, the fluorescence changes of the chemosensor are remarkably specific for citrate in the presence of other anions (even those that exist in high concentration), which meet the selective requirements for practical application. Moreover, the response of the chemosensor toward citrate is fast (response time less than 1 min). In addition, the chemosensor has been used for determination of citrate in urine samples with satisfactory results.