Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 27
Filter
1.
Opt Lett ; 49(10): 2589-2592, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38748112

ABSTRACT

This Letter proposes an optical-pulse-based reconfigurable phase control method, enabling a dual-band phased array receiver to operate in two modes: dual-band-independent operation and dual-band fusion. The method utilizes optical pulses and optical delay to compensate for phase differences across frequency bands. An electrical phase shifter is employed to compensate for phase residual in both bands. All phase operations to both bands are processed concurrently in one link, thereby maintaining inter-band phase coherence. Experimental results verify the ability of dual-band-independent beamforming and inter-band phase coherence maintaining. A four-channel dual-band (X- and Ku-band) phased array antenna (PAA) receiver is constructed to measure PAA patterns and demonstrate band fusion. The pulse compression results in all directions reveal a doubled improvement in range resolution, which shows the potential for enhancement of radar performance.

2.
Mol Brain ; 17(1): 12, 2024 Feb 26.
Article in English | MEDLINE | ID: mdl-38409127

ABSTRACT

BACKGROUND: Autism spectrum disorder (ASD) encompasses a diverse range of neurodevelopmental disorders, but the precise underlying pathogenesis remains elusive. This study aim to explore the potential mechanism of TREM2 in regulating microglia function in ASD. MATERIALS AND METHODS: The offspring rat model of ASD was established through prenatal exposure to valproic acid (VPA), and the behavioral symptoms of the ASD model were observed. On postnatal day (PND) 7 and PND 28, the effects of prenatally exposure to VPA on synaptic development and microglia phenotype of offspring rats were observed. Primary microglia were cultured in vitro. Lentivirus and adenovirus were utilized to interfere with TREM2 and overexpress TREM2. RESULTS: Prenatally VPA exposure induced offspring rats to show typical ASD core symptoms, which led to abnormal expression of synapse-related proteins in the prefrontal cortex of offspring rats, changed the phenotype of microglia in offspring rats, promoted the polarization of microglia to pro-inflammatory type, and increased inflammatory response. The experimental results in vitro showed that overexpression of TREM2 could increase the expression of Gephyrin, decrease the content of CD86 protein and increase the content of CD206 protein. In addition, after the expression of TREM2 was interfered, the content of p-P38 MAPK protein increased and the content of p-ELK-1 protein decreased. CONCLUSION: The protective influence of TREM2 on the VPA-induced ASD model is attributed to its inhibition of the P38 MAPK pathway, this protective effect may be achieved by promoting the polarization of microglia to anti-inflammatory phenotype and improving the neuronal synaptic development.


Subject(s)
Autism Spectrum Disorder , Animals , Female , Pregnancy , Rats , Autism Spectrum Disorder/metabolism , Disease Models, Animal , Microglia/metabolism , p38 Mitogen-Activated Protein Kinases/metabolism , Signal Transduction , Valproic Acid/pharmacology
3.
Ying Yong Sheng Tai Xue Bao ; 34(10): 2655-2662, 2023 Oct.
Article in Chinese | MEDLINE | ID: mdl-37897272

ABSTRACT

To explore the effect of monoculture and mixture sowing artificial grassland on the photosynthetic characteristics of Leymus chinensis and Medicago sativa, we determined the diurnal variation of photosynthetic properties of L. chinensis and M. sativa under different treatments. The results showed that the diurnal changes of net photosynthetic rate, blade temperature and transpiration rate of L. chinensis and M. sativa showed 'unimodal type' in monoculture, the stomatal conductance of M. sativa showed 'unimodal type', and the stomatal conductance and water use efficiency of L. chinensis showed 'bimodal type'. Under the mixed sowing treatment, the diurnal changes of net photosynthetic rate, blade temperature and transpiration rate of L. chinensis and M. sativa showed 'unimodal type', the stomatal conductance and water use efficiency of L. chinensis showed 'unimodal type', and the stomatal conductance of M. sativa showed 'bimodal type'. The peak photosynthetic rate of L. chinensis under mixture was signi-ficantly higher than that under monoculture, being 17.72 and 13.65 µmol CO2·m-2·s-1, respectively. Under monoculture and mixture sowing treatments, the chlorophyll content of L. chinensis was higher than that of M. sativa, nitrogen content of the leaves of L. chinensis was lower than that of M. sativa, and the nitrogen content in the leaves of mixture sowing L. chinensis was significantly higher than that of monoculture sowing L. chinensis, which were 27.60 and 22.55 g·kg-1, respectively. Net photosynthetic rates of L. chinensis and M. sativa were significantly positively correlated with stomatal conductance and transpiration rate, and significantly negatively correlated with intercellular CO2 concentration under different planting methods. Net photosynthetic rate of M. sativa was significantly positively correlated with blade temperature and water use efficiency. In summary, mixed sowing was beneficial to enhance nitrogen content of L. chinensis. Our results provided a theoretical basis for the response of the photosynthetic characteristics of forage to planting mode of artificial grassland.


Subject(s)
Carbon Dioxide , Medicago sativa , Grassland , Photosynthesis/physiology , Poaceae , Plant Leaves/physiology , Water , Nitrogen
4.
Opt Lett ; 48(20): 5324-5327, 2023 Oct 15.
Article in English | MEDLINE | ID: mdl-37831858

ABSTRACT

Temporal alignment between the demultiplexing signal and sampled signal for complex wideband signals greatly increases the difficulty of designing high-speed and high-resolution photonic analog-to-digital converters (PADCs). We present a vector description to decouple the timing skew from the phase frequency response in time-demultiplexing PADC. We demonstrate that the calibration can be optically implemented with true time delay effects and the broadband input can be one-time calibrated through several single-frequency signals. For verification, we configure out a 40 GSa/s PADC with eight-interleaved sub-channels. The timing skew-induced spurs across the whole Nyquist band are effectively suppressed, making the PADC acquire a wideband signal with 16 GHz instantaneous bandwidth. The spurious-free dynamic range (SFDR) is enhanced to ∼55 dB, and the effective number of bits (ENOB) is improved from ∼5.5 bits to ∼8 bits within 20 GHz. It is nearly 1 bit better than the recently reported time-demultiplexing PADC under the comparable input frequencies.

5.
Noncoding RNA ; 9(5)2023 Aug 25.
Article in English | MEDLINE | ID: mdl-37736896

ABSTRACT

The NLRP3 inflammasome plays a pivotal role in regulating inflammation and immune responses. Its activation can lead to an inflammatory response and pyroptotic cell death. This is beneficial in the case of infections, but excessive activation can lead to chronic inflammation and tissue damage. Moreover, while most of the mammalian genome is transcribed as RNAs, only a small fraction codes for proteins. Among non-protein-coding RNAs, long non-coding RNAs (lncRNAs) have been shown to play key roles in regulating gene expression and cellular processes. They interact with DNA, RNAs, and proteins, and their dysregulation can provide insights into disease mechanisms, including NLRP3 inflammasome activation. Here, we systematically analyzed previously published RNA sequencing (RNA-seq) data of NLRP3 inflammasome activation in monocytes/macrophages to uncover inflammasome-regulated lncRNA genes. To uncover the functional importance of inflammasome-regulated lncRNA genes, one inflammasome-regulated lncRNA, ENSG00000273124, was knocked down in an in vitro model of macrophage polarization. The results indicate that silencing of ENSG00000273124 resulted in the up-regulation tumor necrosis factor (TNF), suggesting that this lncRNA might be involved in pro-inflammatory response in macrophages. To make our analyzed data more accessible, we developed the web database InflammasomeDB.

6.
Eur J Pharmacol ; 957: 176018, 2023 Oct 15.
Article in English | MEDLINE | ID: mdl-37634840

ABSTRACT

Acute kidney injury (AKI) is a clinically serious disorder associated with high mortality rates and an increased risk of progression to end-stage renal disease. As an essential supportive treatment for patients with respiratory failure, mechanical ventilation not only save many critically ill patients, but also affect glomerular filtration function by changing renal hemodynamics, neurohumoral and positive end-expiratory pressure, eventually leading to AKI. AMP-activated protein kinase (AMPK), a crucial energy homeostasis regulator, could enhance macrophage phagocytic ability and inhibit inflammation, but whether it can engulf neutrophil extracellular traps (NETs) and alleviate mechanical ventilation-associated AKI is still unclear. In this study, we found that geniposide significantly ameliorated histopathological damage, reduced serum Cre and BUN levels. Besides, geniposide can also induce AMPK activation and enhance macrophage phagocytic ability toward NETs. Moreover, geniposide can markedly reduce the levels of high mobility group box 1 (HMGB1), and these effects were dependent on AMPK-PI3K/Akt signaling. Altogether, these results indicated that geniposide promoted macrophage efferocytosis by inducing AMPK-PI3K/Akt signaling activation, clearing NETs and ameliorating AKI.


Subject(s)
Acute Kidney Injury , Extracellular Traps , Humans , AMP-Activated Protein Kinases , Phosphatidylinositol 3-Kinases , Proto-Oncogene Proteins c-akt , Macrophages , Acute Kidney Injury/drug therapy
7.
Org Biomol Chem ; 21(23): 4881-4892, 2023 Jun 14.
Article in English | MEDLINE | ID: mdl-37259536

ABSTRACT

An aminomethylation reaction of fulleropyrrolidines bearing ketone moieties in the presence of N-unsubstituted fulleropyrrolidines and paraformaldehyde with the aid of p-toluenesulfonic acid afforded a series of scarce pendant fullerene dimers. A simple change of reaction substrates from ketone to ketone-containing fulleropyrrolidines successfully realized the synthesis of a variety of novel pendant fullerene dimers, including those from methyl ketone-containing fulleropyrrolidines, which were considered to produce the known bridged fullerene dimers. It should be noted that pendant fullerene dimers are usually difficult to prepare by other methods and may have promising applications in perovskite solar cells. Density functional theory (DFT) has been employed to elucidate the regioselectivity of methyl ketone-containing fulleropyrrolidines to yield exclusively pendant fullerene dimers by investigating the Gibbs free energy profile of the reaction starting from methyl ketone-containing fulleropyrrolidines and iminium intermediates.

8.
Opt Express ; 30(12): 20580-20588, 2022 Jun 06.
Article in English | MEDLINE | ID: mdl-36224799

ABSTRACT

A scheme of high-resolution inverse synthetic aperture radar (ISAR) imaging based on photonic receiving is demonstrated. In the scheme, the linear frequency modulated (LFM) pulse echoes with 8 GHz bandwidth at the center frequency of 36 GHz are directly sampled with the photonic analog-to-digital converter (PADC). The ISAR images of complex targets can be constructed without detection range swath limitation due to the fidelity of the sampled results. The images of two pyramids demonstrate that the two-dimension (2D) resolution is 3.3 cm × 1.9 cm. Furthermore, the automatic target recognition (ATR) is employed based on the high-resolution experimental dataset under the assistance of deep learning. Despite of the small training dataset containing only 50 samples for each model, the ATR accuracy of three complex targets is still validated to be 95% on a test dataset with the equal number of samples.

9.
Opt Express ; 30(12): 21736-21745, 2022 Jun 06.
Article in English | MEDLINE | ID: mdl-36224886

ABSTRACT

Substantial interests have been attracted in the use of photonic sampling and electronic digitizing for photonic analog-to-digital converter (PADC). However, the nature of that photo-detection with signal holding effects has not been well established. This paper analyzes the equivalence of photonic sampling to signal holding by controlling photo-detection response. In the frequency domain, the high-frequency components generated by the sampling pulse train are folded back into the Nyquist band resulting the signal holding response when the output is digitized. We proposed an approximate response of the photodetector (PD) to verify the theoretical analysis. It is found that the photonic sampling serves as the conventional switch-based sample-and-hold (S&H) circuit in channel-interleaved photonic analog-to-digital converter. In the experiment, the signal holding directly inhibits the timing mismatch without sophisticated calibrations.

10.
Biomed Res Int ; 2022: 2064013, 2022.
Article in English | MEDLINE | ID: mdl-35774277

ABSTRACT

Mycoplasma pneumoniae pneumonia (MPP) represents a common respiratory disease in children patients. Kukoamine A (KuA) is a spermine alkaloid found in the Chinese herb Cortex Lycii radices, which has a variety of pharmacological properties. However, no study has been reported on the role of KuA in MPP. Exosomes, a type of lipid bilayer-enclosed extracellular vesicles, can be delivered to the target cells, where they regulate function and physiology. With the use of human alveolar basal epithelial cells (HABECs) as an in vitro model, in this study, we sought to characterize the changes in levels of superoxide dismutase 2 (SOD2) and proinflammatory cytokines including IL-6 and TNF-α in HABECs in response to exosomes, which were isolated from peripheral blood serum of MPP patients. We found that, compared to normal, MPP patients exhibited a significant up-regulated miR-222-3p. Further, exosomal miR-222-3p downregulated SOD2 activity but promoted nuclear NF-κB activity and expression of IL-6 and TNF-α in HABECs, ultimately leading to an oxidative stress condition. Interestingly, such stimulating effects were attenuated by the pretreatment of KuA. This study suggests a critical role possessed by KuA in MPP by regulating the miR-222-3p/SOD2 axis, which represents a promising strategy for the treatment of MPP.


Subject(s)
MicroRNAs , Mycoplasma pneumoniae , Pneumonia, Mycoplasma , Spermine , Child , Humans , MicroRNAs/genetics , MicroRNAs/metabolism , Mycoplasma pneumoniae/genetics , Pneumonia, Mycoplasma/drug therapy , Pneumonia, Mycoplasma/genetics , Pneumonia, Mycoplasma/metabolism , Spermine/analogs & derivatives , Spermine/pharmacology , Superoxide Dismutase , Tumor Necrosis Factor-alpha/metabolism
11.
Opt Lett ; 47(6): 1355-1358, 2022 Mar 15.
Article in English | MEDLINE | ID: mdl-35290312

ABSTRACT

We demonstrate an automatic target recognition (ATR) scheme based on an improved photonic time-stretched coherent radar (PTS-CR). The reception apertures of the PTS-CR can cover the entire detection range by receiving the echo signal with high repetition rate pulses and increasing the amount of dispersion of the first dispersive medium in the receiver. Two channels with different stretching factors are simultaneously used to restore the signal delay information. Simulated and experimental results verify the feasibility of the new scheme. Finally, based on the improved receiving scheme, PTS-CR successfully performed ATR on four different targets placed on a rotating stage. Combining this with the training of the convolutional neural network (CNN), the recognition accuracy rate is 94.375%.

12.
Opt Express ; 28(26): 39618-39628, 2020 Dec 21.
Article in English | MEDLINE | ID: mdl-33379507

ABSTRACT

We propose a convolutional recurrent autoencoder (CRAE) to compensate for time mismatches in a photonic analog-to-digital converter (PADC). In contrast of other neural networks, the proposed CRAE is generalized to untrained mismatches and untrained category of signals while remaining robust to system states. We train the CRAE using mismatched linear frequency modulated (LFM) signals with mismatches of 35 ps and 57 ps under one system state. It can effectively compensate for mismatches of both LFM and Costas frequency modulated signals with mismatches ranging from 35 ps to 137 ps under another system state. When the spur-free dynamic range (SFDR) of the unpowered PADC decreases from 10.2 dBc to -3.0 dBc, the SFDR of the CRAE-powered PADC is over 31.6 dBc.

13.
Opt Express ; 27(6): 9205-9214, 2019 Mar 18.
Article in English | MEDLINE | ID: mdl-31052728

ABSTRACT

The electronic aperture jitter effect originating from the electronic digitization is investigated in the channel-interleaved photonic analog-to-digital converter (PADC) system. The influence of the electronic aperture jitter to the effective number of bits (ENOB) of the PADC system is extracted and evaluated. According to the theoretical analysis, the electronic aperture jitter can be significantly suppressed by the channel-interleaving scheme. In the experiment, the effect of electronic aperture jitter is measured under different optical-electronic conversion (OEC) bandwidths and channel numbers. It is eventually found that the condition of the OEC bandwidth equaling to the Nyquist frequency of one single channel is critical to optimize the electronic aperture jitter and ENOB.

14.
Opt Lett ; 43(23): 5869-5872, 2018 Dec 01.
Article in English | MEDLINE | ID: mdl-30499962

ABSTRACT

The signal-to-noise ratio (SNR) of the photonic time-stretching receiver in the photonic time-stretch coherent radar (PTS-CR) system is theoretically analyzed. According to the analysis based on the erbium-doped fiber amplifier (EDFA) characteristic, it is found that the SNR is dominantly determined by the input optical power of the EDFA. With the improvement of the SNR of the photonic time-stretching receiver, the radar detection sensitivity is consequently enhanced. Furthermore, a PTS-CR system operating at W band with the ultrabroad bandwidth of 12 GHz is experimentally enabled, leading to the range resolution of ∼1.48 cm in dual-target detection.

15.
Clin Chim Acta ; 484: 105-110, 2018 Sep.
Article in English | MEDLINE | ID: mdl-29842856

ABSTRACT

BACKGROUND: Cyclophilin A (CyPA) is a potential mediator of inflammation. We assessed the predictive value of the first-trimester maternal serum CyPA concentrations for complicated pregnancy. METHODS: The first-trimester serum CyPA concentrations were quantified in 100 women with normal pregnancy and in 351 women with complicated pregnancy, including 102 pre-eclampsia women, 131 gestational hypertension (GH) women and 118 gestational diabetes mellitus (GDM) women. Its association with complicated pregnancy was ascertained using multivariate analysis. RESULTS: Median CyPA concentrations were significantly higher in women developing complicated pregnancy as pre-eclampsia, GH or GDM than in women with normal pregnancy. CyPA concentrations were independently correlated with C-reactive protein concentrations in complicated pregnancy as pre-eclampsia, GH or GDM women. Serum CyPA and body mass index were independently associated with the development of complicated pregnancy as pre-eclampsia, GH or GDM. Serum CyPA possessed significantly high area under receiver operating characteristic curve. Meanwhile, CyPA significantly improved the predictive value of body mass index. CONCLUSIONS: Serum CyPA might be utilized as a potential inflammatory biomarker for complicated pregnancy and assessment of serum CyPA might aid in the prediction of complicated pregnancy.


Subject(s)
Cyclophilin A/blood , Pre-Eclampsia/blood , Pregnancy Complications/blood , Pregnancy Trimester, First/blood , Adult , Biomarkers/blood , Diabetes, Gestational/blood , Female , Humans , Hypertension, Pregnancy-Induced/blood , Multivariate Analysis , Pregnancy , Young Adult
16.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-699514

ABSTRACT

Objective To establish a rapid high performance liquid chromatography(HPLC)method for simultaneous determination of the concentration of total,free and reduced homocysteine (Hcy),glutathione(GSH),cysteine (Cys)and cys-teinylglycine (CysGly). Methods HPLC fluorescence detection method was established under the below conditions. The axci-tation and emission wavelengths was 330 nm and 380 nm respectively;the separation of thiols was achieved by using a C-18 column and the column temperature was 25 ℃;the mobile phase was gradient eluted with the three carboxyl ethyl phosphine (TCEP)as reducing agent and N-1- phenyl maleimide (NPM)as derivatization agent. The HPLC fluorescence detection meth-od was used to measure the thiol concentration in plasma of uraemia patients and healthy people. Results The linear range of total and free Hcy,GSH,Cys and CysGly were 1. 0 - 120. 0,2. 0 - 80. 0,10. 0 - 1500. 0 and 3. 0 - 240. 0 μmol·L - 1 respec-tively;the linear range of reduced Hcy,GSH,Cys and CysGly was 1. 25 - 50. 00,0. 10 - 8. 00,1. 25 - 50. 00 and 0. 01 -4. 00 μmol·L - 1 respectively. The intra-and inter-day ralative standard deviation were less than 5%;the recovery of this meth-od was 80. 1% - 111. 7% . The newly established HPLC fluorescence detection method was successfully applied to determine the total,free and reduced concentration of GSH,Cys,Hcy and CysGly in 34 uraemia patients and 32 healthy people. Conclu-sion A new HPLC fluorescence detection method for the determination of Hcy,GSH,Cys,and CysGly in plasma is developed and this method is accurate and reliable.

17.
Sci Rep ; 7(1): 8041, 2017 08 14.
Article in English | MEDLINE | ID: mdl-28808335

ABSTRACT

Metanephrines (MNs) were suggested as a potential first-line biochemical index for the diagnosis of phaeochromocytomas (PHEO). In this study, we developed a simple electrochemical method for the quantitative measurement of MNs in spot urine samples. As MNs contain a hydroxyphenyl group, they could be oxidized at a certain potential to quinines, which could be further detected by the differential pulse voltammetry (DPV) method using unmodified screen-printed carbon electrode (SPCE). Meanwhile, the solid phase extraction (SPE) technique was used to eliminate the matrix effect in the samples. Consequently, free MNs from the extracted urine sample were screened in a linear range from 0.25 mg/L to 12.5 mg/L. The lowest limit of quantification (LLOQ) for MNs was 0.25 mg/L and the limit of detection (LOD) was 0.05 mg/L. Both the precisions and recoveries were sufficient for clinical applications. The urine samples from 22 patients with PHEO and 63 controls were analyzed by the proposed method. The area under the ROC curve was 0.981 (95% CI, 0.958-1.000) with the sensitivity of 95.5% and the specificity of 92.4% at the cut-off value of 0.404 mg/L in these urine samples. Overall, the proposed method provides a cost-effective, rapid and simple tool for clinical diagnosis of PHEO.


Subject(s)
Metanephrine/urine , Pheochromocytoma/urine , Carbon/chemistry , Electrochemical Techniques/methods , Electrodes , Evaluation Studies as Topic , Humans , Limit of Detection , Sensitivity and Specificity , Solid Phase Extraction/methods
18.
Bioorg Chem ; 69: 129-131, 2016 12.
Article in English | MEDLINE | ID: mdl-27814566

ABSTRACT

Baicalin is one of the active ingredients in the skullcap, with a variety of pharmacological effects, such as blood pressure reduction, sedation, liver-protection, gallbladder-protection, anti-bacteria, and anti-inflammation. In our study, baicalin was first characterized as a LSD1 inhibitor with an IC50 of 3.01µM and showed strong LSD1 inhibitory effect in cells. Baicalin may serve as a template for designing flavone-based LSD1 inhibitors.


Subject(s)
Biological Products/pharmacology , Enzyme Inhibitors/pharmacology , Flavonoids/pharmacology , Histone Demethylases/antagonists & inhibitors , Biological Products/chemical synthesis , Biological Products/chemistry , Cell Line, Tumor , Dose-Response Relationship, Drug , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/chemistry , Flavonoids/chemical synthesis , Flavonoids/chemistry , Histone Demethylases/metabolism , Humans , Molecular Conformation , Structure-Activity Relationship
19.
J Huazhong Univ Sci Technolog Med Sci ; 36(4): 514-518, 2016 Aug.
Article in English | MEDLINE | ID: mdl-27465325

ABSTRACT

The treatments of resectable colorectal liver metastases (CRLM) are controversial. This study aimed to evaluate the relative efficacy and safety of hepatic resection (HR) and radiofrequency ablation (RFA) for treating resectable CRLM. Between January 2004 and May 2010, the enrolled patients were given hepatic resection (HR group; n=32) or percutaneous RFA (RFA group; n=21) as a first-line treatment for CRLM. All the tumors had a maximum diameter of 3.5 cm and all patients had five or less tumors. The patient background, tumor characteristics, cumulative survival rate and recurrence-free survival rate were assessed in both groups. There were significantly more patients with comorbidities in the RFA group than those in the HR group (17 in RFA group vs. 10 in HR group; P<0.000). The mean maximum tumor diameter in the HR group and RFA group was 2.25±0.68 and 1.89±0.62 cm (P=0.054), and the mean number of tumors was 2.28±1.05 and 2.38±1.12 (P=0.744), respectively. The 1-, 3- and 5-year cumulative survival rates in the HR group were 87.5%, 53.1% and 31.3%, respectively, and those in the RFA group were 85.7%, 38.1% and 14.2%, respectively with the differences being not significant between the two groups (P=0.062). The 1-, 3- and 5-year recurrence-free survival rates in the HR group were 90.6%, 56.3% and 28.1%, respectively, and those in the RFA group were 76.1%, 23.8% and 4.8%, respectively, with the differences being significant between the two groups (P=0.036). In conclusion, as HR has greater efficacy than RFA in the treatment of resectable CRLM, we recommend it as the first option for this malignancy.


Subject(s)
Catheter Ablation/methods , Colorectal Neoplasms/surgery , Liver Neoplasms/surgery , Liver/surgery , Aged , Colorectal Neoplasms/pathology , Colorectal Neoplasms/radiotherapy , Female , Hepatectomy/methods , Humans , Liver/pathology , Liver Neoplasms/pathology , Liver Neoplasms/radiotherapy , Liver Neoplasms/secondary , Male , Middle Aged , Neoplasm Metastasis , Treatment Outcome
20.
Cell Physiol Biochem ; 38(1): 185-93, 2016.
Article in English | MEDLINE | ID: mdl-26784898

ABSTRACT

BACKGROUND/AIMS: Human SIRT1 is reported to be involved in tumorgenesis, mainly due to its modulating effect on p53 by deacetylation on lysine382. A large quantity of SIRT1 inhibitors was applied in chemotherapeutic study, but few of them were applied into clinical trials. METHODS AND RESULTS: In the current study, a novel series of compounds with 1,4-bispiperazinecarbodithioic acid methyl esters scaffold were characterized to have inhibitory potency to SIRT1 by molecular docking and biochemical evaluation. Further cell level study revealed that one of the most potent SIRT1 inhibitors, compound 3a, is cell active. It can upregulate the amount of p53 by accumulating the K382 acetylation of p53, which lead to the stabilization of p53 in human gastric cancer cell line MGC-803 cells. Meanwhile, we also found compound 3a can inactivate SIRT2 in cells, which suggests the compound as a non-selective SIRT inhibitor. CONCLUSION: All these findings indicate that compound 3a is a potent, reversible and cell active SIRT1 inhibitor and deserves further investigation as an anticancer agent or a biological tool.


Subject(s)
Gene Expression Regulation/drug effects , Sirtuin 1/antagonists & inhibitors , Thiocarbamates/pharmacology , Triazoles/pharmacology , Acetylation/drug effects , Binding Sites , Cell Line, Tumor , Enzyme Inhibitors/pharmacology , Humans , Molecular Docking Simulation , Protein Binding/drug effects , Protein Structure, Tertiary , Sirtuin 1/metabolism , Sirtuin 2/antagonists & inhibitors , Sirtuin 2/metabolism , Thiocarbamates/chemistry , Triazoles/chemistry , Tumor Suppressor Protein p53/genetics , Tumor Suppressor Protein p53/metabolism
SELECTION OF CITATIONS
SEARCH DETAIL
...