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1.
ACS Chem Biol ; 2021 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-33955736

RESUMO

A challenge for sensors targeting specific enzymes of interest in their native environment for direct imaging is that they rationally exploit a highly selective fluorescent probe with a high binding affinity to provide real-time detection. Immunohistochemical staining, proteomic analysis, or recent enzymatic fluorescent probes are not optimal for tracking specific enzymes directly in living cells. Herein, we introduce the concept of designing a highly effective fluorescent probe (BVQ1814) targeting phosphodiesterase 10A with a highly potent affinity and a >1000-fold subfamily selectivity by gaining insights into the three-dimensional structural information of the active site of the catalytic pocket. BVQ1814 showed an outstanding binding affinity for PDE10A in vitro and specifically detected PDE10A in living cells, indicating that most PDE10A was probably distributed in the lysosomes. We validated the PDE10A distribution in stable mCherry-PDE10A-overexpressing HepG2 cells. This probe delineated the profile of PDE10A in tissue sections and exhibited a remarkable therapeutic effect as a PDE10A inhibitor for treating pulmonary arterial hypertension. This concept will open up a new avenue for designing a highly effective fluorescent probe for tracking receptor proteins by taking full advantage of the structural information in the ligand-binding pocket of the target of interest.

2.
J Colloid Interface Sci ; 599: 168-177, 2021 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-33933791

RESUMO

Currently, engineering non-precious NiFe layered double hydroxide (NiFe-LDH) electrocatalysts with excellent oxygen evolution performances at high current densities is highly critical to promoting electrolytic water splitting producing hydrogen for large-scale commercial applications. Herein, an intrigued oxygen vacancy-rich Fe(Ⅱ)-incorporated NiFe-LDH containing electroactive high-valence ferritic species is successfully grown on Ni foam (Fe2+-NiFe-LDH-EO6 h@NF) through an elaborate two-step route including hydrothermal and electrooxidation, and utilized as a high-efficiency elctrocayalyst of alkaline water oxidation possessing abundant exposed active sites, excellent intrinsic catalytic activity and superior durability. Therefore, the Fe2+-NiFe-LDH-EO6 h@NF electrocatalyst towards oxygen evolution reaction (OER) enables the low overpotentials of 239, 285 and 350 mV for the current densities of 10, 100 and 500 mA cm-2, respectively, a small Tafel slope of 48.3 mV dec-1, the low onset potential of 1.451 V, and retains the catalytic activity for 40 h at the large current density of 500 mA cm-2 as well as owns the high turnover frequency (TOF) value of 0.93 s-1 at the overpotential of 300 mV. This work provides a promising avenue to improve the OER performances of NiFe-LDH electrocatalyst for practical applications.

3.
Artigo em Inglês | MEDLINE | ID: mdl-33945259

RESUMO

A supramolecular polymer, poly(N-acryloyl glycinamide) (PNAGA), with a bisamide group on each side of the chain forming multiple amide-hydrogen bonds was synthesized in this work as a binder for silicon (Si)-based anodes. This supramolecular polymer binder with improved mechanical properties presents good interfacial adhesion with Si particles forming hydrogen bonds and enhances the adhesive strength between the electrode material film and the copper current collector. Benefiting from the highly stable inter- and intramolecular multiple amide-hydrogen bonds of the PNAGA binder, the electrode structure maintains integrity and a stable solid electrolyte interphase (SEI) layer is formed on the surface of Si particles. The effect of different binders on the composition of the SEI film was also investigated by X-photoelectron spectroscopy (XPS) characterization. In comparison with polyacrylamide (PAM), which has a similar structure to PNAGA, and the traditional sodium alginate (SA) binder, the Si electrode containing the PNAGA binder shows improved electrochemical performance. The capacity retention is 84% after 100 cycles at 420 mA g-1, and the capacity remains at 1942.6 mAh g-1 after 400 cycles at 1260 mA g-1. Even with a mass loading of 1.2 mg cm-2 Si, the electrode with the PNAGA binder exhibits high initial areal capacity (2.64 mAh cm-2) and good cycling performance (81% capacity retention after 50 cycles). Moreover, the application of the PNAGA binder also brings a stable cycle performance to the commercial Si-graphite (SiC) anode material.

4.
Int Urol Nephrol ; 2021 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-33797710

RESUMO

OBJECTIVE: To evaluate the effect of myofascial manipulation by observing the changes in pelvic floor myofascial scores and electromyography (EMG) data before and after treatment. METHODS: A total of 106 patients with myofascial pelvic pain (MFPP) were enrolled in a treatment group, and 50 healthy women were enrolled in a control group. The changes in the pelvic floor EMG data in the two groups were monitored by using Myo Trac before and after treatment. Pelvic trigger points and their distribution in the MFPP patients were examined using a finger pressure test. The visual analogue scale was used to assess the severity of pain in both groups. After one course of manipulation (twice per week for a total of 10 times), the effectiveness of the manipulation was analyzed by comparing the changes in pain scores before and after treatment. RESULTS: The main symptoms of MFPP in the study sample consisted of lower abdominal pain, lumbosacral pain, or mixed pain, which together accounted for 67% of all symptoms. Patients often had multiple trigger points, covering 47.17% of the body. The differences between the treatment group and control group in the changes in pelvic floor muscle strength, number of pain points, pain scores, resting EMG of pelvic floor muscles, and relaxation time after muscle contraction were all statistically significant (P < 0.05). The differences between the pre-treatment and post-treatment groups in the changes in pelvic floor muscle strength, number of pain points, pain scores, resting EMG of pelvic floor muscles, and relaxation time after muscle contraction were all statistically significant (P < 0.05) CONCLUSION: Manipulation is an effective treatment for MFPP and is worthy of further clinical promotion.

5.
J Cardiothorac Surg ; 16(1): 91, 2021 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-33865420

RESUMO

INTRODUCTION: Totally endoscopic technique has been widely used in cardiac surgery, and minimally invasive totally endoscopic mitral valve surgery has been developed as an alternative to median sternotomy for many patients with mitral valve disease. In this study, we describe our experience about a modified minimally invasive totally endoscopic mitral valve surgery and reported the preliminary results of totally endoscopic mitral valve surgery. The aim of this retrospective study is to evaluate the results of totally endoscopic technique in mitral valve surgery. MATERIAL AND METHODS: We retrospectively reviewed the profiles of 188 patients who were treated for mitral valve disease by modified totally endoscopic mitral valve surgery at our institution between January 2019 and December 2020. The procedure was performed under endoscopic right minithoracotomy and with femoro-femoral cannulation using the single two-stage venous cannula. RESULTS: A total of 188 patients underwent total endoscopic mitral valve surgery. Fifty-six patients had concomitant tricuspid valvuloplasty, 11 patients underwent concomitant ablation of atrial fibrillation and atrial septal defect repair was performed in three patients. Only one patient postoperatively died of multi-organ failure. Two patients were converted to median sternotomy. Except for one patient underwent operation to stop the bleeding from the incision site, no other serious complications nor reintervention occurred during the follow-up period. CONCLUSIONS: The modified totally endoscopic mitral valve surgery performed at our institution is technically feasible and safe with the same efficacy as reported studies.

6.
Chem Commun (Camb) ; 2021 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-33908479

RESUMO

Zirconium (Zr)-based porphyrinic metal-organic frameworks (PCN-223-M) were employed as the electrocatalysts to explore the effect of uncoordinated Zr sites on the performance of the CO2 reduction reaction (CO2RR). PCN-223-AA with the lowest uncoordinated number of 0.79 exhibited the highest FE(CO) of 90.7%. It was demonstrated that the catalytic performance of PCN-223-M showed negative correlation to the uncoordinated Zr sites. This research provided a rational strategy to design efficient MOF electrocatalysts with few uncoordinated metal sites for highly selective CO2RR.

7.
Dalton Trans ; 50(16): 5442-5445, 2021 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-33861226

RESUMO

Two new zinc phosphites were prepared using the amino acid alanine as a structure-directing agent. They have tubular and ladder-like structures, exhibiting blue fluorescence upon UV light irradiation. Notably, the tubular structure is unprecedented in metal phosphite systems. The compound is a nonlinear optically active solid with a second-harmonic generation efficiency of about 1.2 times that of KH2PO4 (KDP).

8.
J Int Med Res ; 49(4): 3000605211005878, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33887984

RESUMO

AIM: This retrospective study aimed to evaluate the predictive value of serum cancer antigen 125 (CA125) levels before hormone replacement therapy on pregnancy outcomes in women with adenomyosis undergoing frozen embryo transfer. METHODS: A total of 509 women with adenomyosis were screened and 84 patients receiving a total of 114 cycles of frozen embryo transfer were included, based on the inclusion and exclusion criteria. Patients were divided into two groups based on their CA125 levels (≤ or >35 IU/mL) before hormone replacement therapy. The basic characteristics and main outcomes of the two groups were compared. Receiver operating characteristic curve and subgroup analyses were also conducted. RESULTS: There were no significant differences in clinical outcomes of frozen embryo transfer cycles in patients with different serum CA125 levels before hormone replacement therapy. Receiver operating characteristic curve analysis demonstrated that CA125 levels before hormone replacement therapy were not predictive of clinical pregnancy outcomes. CONCLUSIONS: Serum CA125 levels before hormone replacement therapy are not associated with the clinical outcomes of frozen embryo transfer among women with adenomyosis.

9.
Artigo em Inglês | MEDLINE | ID: mdl-33860576

RESUMO

Due to their unique afterglow ability, long wavelength light activatable persistent luminescence (PersL) nanoparticles (PLNPs) have been emerging as an important category of imaging probes. In particular, long wavelength LED light has been shown to be effective in recharging these nanoparticles. However, finding a simple and effective method to amplify such renewable PersL signals under long wavelength light is still a key challenge. Herein, we discovered that a dye-sensitization strategy was able to effectively boost the renewable PersL signals of the NIR emitting ZnGa 2 O 4 :Cr 3+ (ZGC)) under long wavelength LED light. Moreover, as a proof-of-principle tumorectomy demonstration, this new class of dye sensitized ZGC enabled simultaneous intraoperative anatomic tumor navigation and effective microscopic detection of tumor cells in pathological diagnosis. Thus, this work will offer a simple way to the development of PLNPs with enhanced luminescence and provides new opportunities for a wide variety of biophotonic and photonic applications.

10.
Angle Orthod ; 2021 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-33848325

RESUMO

OBJECTIVES: To compare preparation time and 1-year Invisalign aligner attachment survival between a flowable composite (FC) and a packable composite (PC). MATERIALS AND METHODS: Fifty-five participants (13 men and 42 women, mean age ± SD: 24.2 ± 5.9 years) were included in the study. Ipsilateral quadrants (ie, maxillary and mandibular right, or vice versa) of attachments were randomly assigned to the FC group (Filtek Z350XT Flowable Restorative) and the PC group (Filtek Z350XT Universal Restorative) by tossing a coin. The primary outcome was preparation time. The secondary outcome was time to the first damage of an attachment. Preparation times were compared using the paired t-test, and the survival data were analyzed by the Cox proportional hazards model with a shared frailty term, with α = .05. RESULTS: The preparation times were significantly shorter with the FC (6.22 ± 0.22 seconds per attachment) than with the PC (32.83 ± 2.16 seconds per attachment; P < .001). The attachment damage rates were 14.79% for the FC and 9.70% for the PC. According to the Cox models, attachment damage was not significantly affected by the attachment material, sex, arch, tooth location, attachment type, presence of overbite, or occurrence of tooth extraction. CONCLUSIONS: The use of a FC may save time as compared with the use of a PC. With regard to attachment survival, there was no significant difference between the two composites. None of the covariates of attachment materials (sex, arch, tooth location, attachment type, presence of overbite, oir occurrence of tooth extraction) affected attachment damage.

11.
Cortex ; 139: 60-72, 2021 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-33836303

RESUMO

Humor is a ubiquitous aspect of human behavior that is infrequently the focus of neuroscience research. To localize human brain structures associated with the experience of humor, we conducted quantitative activation likelihood estimate (ALE) meta analyses of 57 fMRI studies (n = 1248) reporting enhanced regional brain activity evoked by humorous cues versus matched control cues. We performed separate ALE analyses of studies that employed picture-driven, text-based, and auditory laughter cues to evoke humor. A primary finding was that complex humor activates supramodal areas of the brain strongly associated with emotional processes, including bilateral amygdala and inferior frontal gyrus. Moreover, activation in brain regions associated with language, semantic knowledge, and theory of mind were differentially modulated by text and picture-driven humor cues, while hearing laughter enhances activation in auditory association cortex. The identification of humor-driven brain networks has the potential to expand brain-derived models of human emotion and could provide useful targets in translational research and therapy.

12.
Nat Immunol ; 22(5): 586-594, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33859405

RESUMO

Two microglial TAM receptor tyrosine kinases, Axl and Mer, have been linked to Alzheimer's disease, but their roles in disease have not been tested experimentally. We find that in Alzheimer's disease and its mouse models, induced expression of Axl and Mer in amyloid plaque-associated microglia was coupled to induced plaque decoration by the TAM ligand Gas6 and its co-ligand phosphatidylserine. In the APP/PS1 mouse model of Alzheimer's disease, genetic ablation of Axl and Mer resulted in microglia that were unable to normally detect, respond to, organize or phagocytose amyloid-ß plaques. These major deficits notwithstanding, TAM-deficient APP/PS1 mice developed fewer dense-core plaques than APP/PS1 mice with normal microglia. Our findings reveal that the TAM system is an essential mediator of microglial recognition and engulfment of amyloid plaques and that TAM-driven microglial phagocytosis does not inhibit, but rather promotes, dense-core plaque development.

13.
Pharmacol Res Perspect ; 9(3): e00764, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33929082

RESUMO

Xanthine oxidase (XO) competes with thiopurine S-methyltransferase (TPMT) and hypoxanthine guanine phosphoribosyltransferase (HPRT) to metabolize azathioprine (AZA)/6-mercaptopurine (6-MP) in vivo. A retrospective investigation was performed to detect the activity of XO in thiopurine curative Chinese inflammatory bowel disease (IBD) patients. We also evaluated whether a relationship between XO activity and incidence of thiopurine-induced adverse effects (AEs) existed. Clinical data and blood samples were collected from 140 IBD patients before receiving AZA/6-MP therapy, and the erythrocyte XO activity was measured. The XO activities of all patients were 20.29 ± 4.43 U/g Hb. No sex difference in XO activity was observed (p = .728), and the XO activity showed no difference between the UC and CD patients (p = .082). AEs were observed in 41 (29.3%) patients including leukopenia (26, 18.57%), gastrointestinal intolerance (11, 7.86%), flu-like symptom (5, 3.57%), alopecia (5, 3.57%), and hepatotoxicity (1, 0.71%). XO activity was significantly lower in the patients with AEs than in those without AEs (18.40 ± 3.73 vs. 21.07 ± 4.48 U/g Hb, p = .001), especially in the patients with leukopenia (18.29 ± 3.68 vs. 21.07 ± 4.48 U/g Hb, p = .004). However, no significant difference in XO activity was found between patients with and without other AEs. Decreased XO activity was observed in the patients who developed flu-like symptoms (17.58 ± 3.50 U/g Hb) and alopecia (18.67 ± 2.91 U/g Hb) compared to those who did not, although the differences did not reach statistical significance. These findings suggested that patients with low XO expression might have a high risk of thiopurine-induced toxicity.

14.
Artigo em Inglês | MEDLINE | ID: mdl-33819929

RESUMO

AIM: Androgens have been reported to be associated with female fertility. The mean serum testosterone concentration in the patients with endometriosis was reported to be significantly lower than that without endometriosis. Our study was designed to investigate the influence of basal serum testosterone levels on the clinical outcome of in vitro fertilization (IVF) in the patients with III-IV stage endometriosis. METHODS: This retrospective cohort study included 407 patients with III-IV stage endometriosis diagnosed by laparoscopic surgery. We studied the association of the basal serum testosterone level and the reproductive outcome of IVF. RESULTS: The basal serum testosterone concentration was significantly higher in the pregnant group of patients with III-IV stage endometriosis. The further analyses demonstrated that the implantation rate of the basal serum testosterone concentration < 0.305 ng/mL group was significantly lower than the testosterone ≥ 0.305 ng/mL group (24.1% vs. 32.7%, p = 0.007). The clinical pregnancy and live birth rate of the basal serum testosterone < 0.305 ng/mL group were also lower than that of the testosterone ≥ 0.305 ng/mL group. Both initial and total dose of gonadotropins in the testosterone <0.305 ng/mL group are significantly higher than that of the testosterone ≥0.305 ng/mL group. CONCLUSIONS: Our study demonstrated, for the first time, that the basal serum testosterone <0.305 ng/mL had an adverse impact on pregnancy outcomes of IVF-embryo transfer in the patients with III-IV stage endometriosis. Besides, the basal serum testosterone is also helpful in making individual stimulation protocol for the patients with advanced endometriosis before entering IVF cycles.

15.
J Am Chem Soc ; 2021 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-33900066

RESUMO

Although BaTiO3 is one of the most famous lead-free piezomaterials, it suffers from small spontaneous and low Curie temperature. Chemical pressure, as a mild way to modulate the structures and properties of materials by element doping, has been utilized to enhance the ferroelectricity of BaTiO3 but is not efficient enough. Here, we report a promoted chemical pressure route to prepare high-performance BaTiO3 films, achieving the highest remanent polarization, Pr (100 µC/cm2), to date and high Curie temperature, Tc (above 1000 °C). The negative chemical pressure (∼-5.7 GPa) was imposed by the coherent lattice strain from large cubic BaO to small tetragonal BaTiO3, generating high tetragonality (c/a = 1.12) and facilitating large displacements of Ti. Such negative pressure is especially significant to the bonding states, i.e., hybridization of Ba 5p-O 2p, whereas ionic bonding in bulk and strong bonding of Ti eg and O 2p, which contribute to the tremendously enhanced polarization. The promoted chemical pressure method shows general potential in improving ferroelectric and other functional materials.

16.
Food Chem ; 355: 129681, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-33799247

RESUMO

In this work, an enteric soluble alginate was proposed to improve the absorption efficiency of cyanidin-3-O-glucoside (C3G) through molecular self-assembly. Under the optimized conditions, the obtained low-viscosity alginate (LVA) was released completely during the simulated gastrointestinal digestion and an LVA-C3G complex with 84.2% binding efficiency was acquired. Fourier transform infrared spectroscopy displayed that the characteristic spectrum of C3G had disappeared after the LVA conjugation. Furthermore, based on the analysis of scanning electron microscopy and differential scanning calorimetry, a porous network structure and the shifted endothermic peak in the thermograms were observed, further confirming the formation of a complex between LVA and C3G. The results of simulated gastrointestinal digestion reveal that the LVA assembly significantly (p < 0.05) improved the bioaccessibility of C3G. Correspondingly, the C3G level in mouse plasma was increased by 27.4% in the C3G-LVA group. This suggests the suitability of LVA as an oral delivery vehicle for dietary anthocyanins.

17.
Cell Stem Cell ; 2021 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-33915081

RESUMO

The exocrine pancreas, consisting of ducts and acini, is the site of origin of pancreatitis and pancreatic ductal adenocarcinoma (PDAC). Our understanding of the genesis and progression of human pancreatic diseases, including PDAC, is limited because of challenges in maintaining human acinar and ductal cells in culture. Here we report induction of human pluripotent stem cells toward pancreatic ductal and acinar organoids that recapitulate properties of the neonatal exocrine pancreas. Expression of the PDAC-associated oncogene GNASR201C induces cystic growth more effectively in ductal than acinar organoids, whereas KRASG12D is more effective in modeling cancer in vivo when expressed in acinar compared with ductal organoids. KRASG12D, but not GNASR201C, induces acinar-to-ductal metaplasia-like changes in culture and in vivo. We develop a renewable source of ductal and acinar organoids for modeling exocrine development and diseases and demonstrate lineage tropism and plasticity for oncogene action in the human pancreas.

18.
World J Gastroenterol ; 27(7): 641-653, 2021 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-33642834

RESUMO

BACKGROUND: Transient elastography (FibroScan) is a new and non-invasive test, which has been widely recommended by the guidelines of chronic hepatitis B virus (HBV) management for assessing hepatic fibrosis staging. However, some confounders may affect the diagnostic accuracy of the FibroScan device in fibrosis staging. AIM: To evaluate the diagnostic value of the FibroScan device and the effect of hepatic inflammation on the accuracy of FibroScan in assessing the stage of liver fibrosis in patients with HBV infection. METHODS: The data of 416 patients with chronic HBV infection who accepted FibroScan, liver biopsy, clinical, and biological examination were collected from two hospitals retrospectively. Receiver operating characteristic (ROC) curves were used to analyze the diagnostic performance of FibroScan for assessing the stage of liver fibrosis. Any discordance in fibrosis staging by FibroScan and pathological scores was statistically analyzed. Logistic regression and ROC analyses were used to analyze the accuracy of FibroScan in assessing the stage of fibrosis in patients with different degrees of liver inflammation. A non-invasive model was constructed to predict the risk of misdiagnosis of fibrosis stage using FibroScan. RESULTS: In the overall cohort, the optimal diagnostic values of liver stiffness measurement (LSM) using FibroScan for significant fibrosis (≥ F2), severe fibrosis (≥ F3), and cirrhosis (F4) were 7.3 kPa [area under the curve (AUC) = 0.863], 9.7 kPa (AUC = 0.911), and 11.3 kPa (AUC = 0.918), respectively. The rate of misdiagnosis of fibrosis stage using FibroScan was 34.1% (142/416 patients). The group of patients who showed discordance between fibrosis staging using FibroScan and pathological scores had significantly higher alanine aminotransferase and aspartate aminotransferase levels, and a higher proportion of moderate to severe hepatic inflammation, compared with the group of patients who showed concordance in fibrosis staging between the two methods. Liver inflammation activity over 2 (OR = 3.53) was an independent risk factor for misdiagnosis of fibrosis stage using FibroScan. Patients with liver inflammation activity ≥ 2 showed higher LSM values using FibroScan and higher rates of misdiagnosis of fibrosis stage, whereas the diagnostic performance of FibroScan for different fibrosis stages was significantly lower than that in patients with inflammation activity < 2 (all P < 0.05). A non-invasive prediction model was established to assess the risk of misdiagnosis of fibrosis stage using FibroScan, and the AUC was 0.701. CONCLUSION: Liver inflammation was an independent risk factor affecting the diagnostic accuracy of FibroScan for fibrosis stage. A combination of other related non-invasive factors can predict the risk of misdiagnosis of fibrosis staging using FibroScan.

19.
J Mater Chem B ; 9(11): 2666-2673, 2021 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-33650620

RESUMO

Mitochondria are the main sites for the production of hypochlorite (OCl-). The protein adenine nucleotide translocase (ANT) is located in the inner mitochondria membrane, which is mainly participated in the transportation of ions and metabolites. At the cellular organelle level, overexpression of ANT is associated with enhanced production of OCl-, however, abnormal levels of OCl- cause redox imbalance and loss of function of mitochondria. Herein, a novel mitochondria-targeted ratiometric fluorescent probe Mi-OCl-RP has been developed. Molecular docking calculation suggested a potential molecular target for the probe in the ANT, and the high binding energy (-8.58 kcal mol-1) may explain the high mitochondria selectivity of Mi-OCl-RP. The unique probe exhibits excellent spectral properties including ratiometric fluorescence response signals to OCl- (within 7 s), high selectivity and sensitivity, and a large Stokes shift (278 nm). In addition, the colocalization coefficient confirms that Mi-OCl-RP can effectively target mitochondria. Furthermore, Mi-OCl-RP has low toxicity and good permeability, and was successfully employed in ratiometric imaging of OCl-in vivo, affording a robust molecular tool for investigating the biological functions of OCl- in living systems.

20.
Biochem Pharmacol ; 188: 114525, 2021 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-33744226

RESUMO

The dysregulation of glycolysis leads to serials of disease. Rabeprazole is a representative of proton pump inhibitors and widely used in anti-ulcer treatment. However, the function of Rabeprazole on glycolysis in gastric epithelial cells remained to be identified. In this study, 30(Helicobacter pylori)H. pylori-negative cases and 26H. pylori-positive cases treated with Rabeprazole were recruited. The qPCR and Western blotting results showed that Rabeprazole suppressed cell proliferation by inhibition of HK2-mediated glycolysis in BGC823 cells, leading to decrease glucose uptake and lactate production in a dose-dependent way. Furthermore, the phosphorylation of signal transducer and activator of transcription 3 (STAT3) was drastically reduced in response to Rabeprazole stimulation, leading to attenuate STAT3 nuclear translocation. Luciferase and Chromatin immunoprecipitation (ChIP) analysis showed that Rabeprazole treatment led to a significant inhibition of the binding of STAT3 to the promoter of the HK2 gene, repressing transcriptional activation of HK2. Moreover, the ectopic expression of STAT3 in BGC823 cells resulted in recovery of HK2 transactivation and cell proliferation in Rabeprazole-treated cells. Most importantly, HK2 expression was significantly increased in H. pylori-infected gastric mucosa. These findings suggested that Rabeprazole inhibited cell proliferation by targeting STAT3/HK2 signaling-mediated glucose metabolism in gastric epithelial cells. Therefore, targeting HK2 is an alternative strategy in improving the treatment of patients with H. pylori infection.

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