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1.
Orthop Surg ; 2020 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-32053281

RESUMO

OBJECTIVE: To evaluate the computational biomechanical analysis of intra-articular calcaneal fractures with different fixation status of the sustentaculum plate screw, when the finite element modeling of calcaneal fractures were fixed by the lateral locking plate. METHODS: The normal right foot of a male (age: 36 years; height: 174 cm; body weight: 65 kg) was scanned by the CT scanner. As the computational biomechanical study, the three-dimensional finite element model of the simplified Sanders type-II calcaneal fracture was built. Fixation with the lateral calcaneal locking plate and screws was simulated using a finite element software package according to clinical operation. According to the different placement of the sustentaculum plate screw, the models were categorized as the accurate fixation group, marginal fixation group, and non-fixation group. The loading of 650 N with the vertical axial compression was applied to simulate the standing phase with single foot. The Von Mises stress distribution, maximal displacement, and contact area of the subtalar joint were analyzed among three groups. RESULTS: The pressure distribution of the subtalar joint facet was inhomogeneous. The stress concentration of the calcaneus was located at the medial zone of the posterior subtalar joint facet. The peak Von Mises stress distribution in three groups was similar at the subtalar joint facet of 4.9 MPa, 5.1 MPa, and 5.4 MPa. In the accurate fixation group, the contact area on the posterior articular facet was 277.1 mm2 ; the maximal displacement was 0.18 mm. The contact area of the marginal fixation group was 265.3 mm2 on the posterior facet, where the maximal displacement was 0.23 mm. In the non-fixation group, the contact area was 253.8 mm2 ; the maximal displacement was 0.25 mm. There was a slight change in the contact area of the subtalar joint and no prominent displacement of the calcaneus could be detected among the three groups. CONCLUSIONS: The biomechanical results, including the peak stress distribution, contact area, and maximal displacement of subtalar joint, were similar whether the screw is placed exactly within the sustentaculum tali or not, when the calcaneal fractures were fixed by the lateral locking plate. The sustentaculum plate screw had less effect on the biomechanical performance of the calcaneus.

2.
Biomed Environ Sci ; 33(1): 19-29, 2020 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-32029055

RESUMO

Objective: The present study aimed to investigate the association of red meat usual intake with metabolic syndrome (MetS), and explore the contribution of red meat usual intake to serum ferritin. Methods: Based on the data from the longitudinal China Health and Nutrition Survey (CHNS), 2,797 healthy adults aged 18-75 years without hypertension, diabetes, and MetS were selected in 2009 as subjects and follow-up studies were carried out till 2015. We used the National Cancer Institute (NCI) method to estimate the usual intake of foods. Multivariable logistic regressions were performed to evaluate the association between red meat usual intake and the risk of MetS. Quantile regression analysis was used to study the relationship between red meat consumption and serum ferritin levels. Results: After adjusting for potential confounders, red meat, and fresh red meat were positively associated with the risk of MetS ( RR = 1.41, 95% CI: 1.05-1.90 and RR = 1.37, 95% CI: 1.02-1.85, respectively). These relationships showed increasing trend ( P < 0.05). The level of serum ferritin increased significantly with the number of MetS components ( P < 0.05). The quantile regression analysis showed that red meat and fresh red meat usual intake had a significant positive association with serum ferritin levels across the entire conditional serum ferritin distribution ( P < 0.05). Processed red meat did not exhibit a similar association. Conclusion: Higher red meat usual intake was associated with an increased risk of MetS and elevated serum ferritin levels.

3.
Ultrasound Med Biol ; 46(4): 981-991, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31980291

RESUMO

The objective of this study was to evaluate the inter-operator reproducibility of strain elastography (SE) and shear wave elastography (SWE) in three groups: all lesions, benign lesions and malignant lesions. Ninety-one lesions from ninety-one women were examined by SE and SWE from January 2017 to December 2017 by two radiologists. The reproducibility of elastic score, SE strain ratio and SWE Young's modulus between operators was prospectively evaluated. There was good agreement on elasticity score, with κ values of 0.711, 0.640 and 0.766. The intra-class correlation coefficients of the strain ratio, mean elastic modulus (Emean), maximum elastic modulus (Emax) and elastic modulus standard deviation (Esd) ranged from 0.723-0.876, which indicated good and excellent agreement. We concluded that both SE and SWE had good reproducibility among different operators using the same probe in the same ultrasound instrument. Strain elasticity score was more consistent among operators in malignant breast tumors. There was better agreement on strain elastic ratio and shear wave elasticity among operators in benign breast lesions.

4.
J Am Soc Nephrol ; 31(1): 40-53, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31666297

RESUMO

BACKGROUND: In Goodpasture disease, the noncollagenous domain 1 of the α3 chain (α3NC1) of type IV collagen is the main target antigen of antibodies against glomerular basement membrane (GBM). We previously identified a nephritogenic epitope, P14 (α3127-148), that could induce crescentic nephritis in WKY rats, and defined its core motif. Designing a modified peptide, replacing critical pathogenic residues with nonpathogenic ones (on the basis of homologous regions in α1NC1 chain of type IV collagen, known to be nonpathogenic), might provide a therapeutic option for anti-GBM GN. METHODS: We synthesized a modified peptide, replacing a single amino acid, and injected it into α3-P14-immunized rats from day 0 (the early-treatment group) or a later-treatment group (from days 17 to 21). A scrambled peptide administrated with the same protocol served as a control. RESULTS: The modified peptide, but not the scrambled peptide, attenuated anti-GBM GN in both treatment groups, and halted further crescent formation even after disease onset. Kidneys from the modified peptide-treated rats exhibited reductions in IgG deposits, complement activation, and infiltration by T cells and macrophages. Treatment also resulted in an anti-inflammatory cytokine profile versus a proinflammatory profile for animals not receiving the modified peptide; it also reduced α3-P14-specific T cell activation, modulated T cell differentiation by decreasing Th17 cells and enhancing the ratio of Treg/Th17 cells, and inhibited binding of α3-P14 to antibodies and MHC II molecules. CONCLUSIONS: A modified peptide involving alteration of a critical motif in a nephritogenic T cell epitope alleviated anti-GBM GN in a rat model. Our findings may provide insights into an immunotherapeutic approach for autoimmune kidney disorders such as Goodpasture disease.

5.
Appl Microbiol Biotechnol ; 104(3): 1187-1199, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31834438

RESUMO

A microbial floc consisting of a community of microbes embedded in extracellular polymeric substances matrix can provide microbial resistances to toxic chemicals and harsh environments. Phenol is a toxic environmental pollutant and a typical lignin-derived phenolic inhibitor. In this study, we genetically engineered Escherichia coli cells by expressions of diguanylate cyclases (DGCs) to promote proteinaceous and aliphatic biofloc formation. Compared with the planktonic E. coli cells, the biofloc-forming cells improved phenol removal rate by up to 2.2-folds, due to their substantially improved tolerance (up to 149%) to phenol and slightly enhanced cellular activity (20%) of phenol hydroxylase (PheH). The engineered bioflocs also improved E. coli tolerance to other toxic compounds such as furfural, 5-hydroxymethylfurfural, and guaiacol. Additionally, the strategy of the engineered biofloc formation was applicable to Pseudomonas putida and enhanced its tolerance to phenol. This study highlights a strategy to form engineered bioflocs for improved cell tolerance and removal of toxic compounds, enabling their universality of use in bioproduction and bioremediation.

6.
Eur J Med Chem ; 185: 111839, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31708185

RESUMO

The ligustrazine - betulin derivative (TB), TB amino acids derivatives (TB-01 - TB-09) and TB dipeptide derivatives (TB-10 - TB-18) were designed and synthesized. And their in vitro cytotoxic activities were evaluated against four cancer cell lines (Hela, HepG2, BGC-823 and HT-29) and normal cells MDCK by standard methylthiazol tetrazolium (MTT) assay. Most of them demonstrated better antitumor activity than the relevant material betulin. Among them, compound TB-01 showed the best anti-tumor effect on the cancer cells and the lowest toxicity on the normal cells. For example, the cytotoxicity of TB-01 against the cancer cells (mean IC50 = 4.86 ±â€¯1.16 µM) was 3-fold higher than that against the normal cells MDCK (IC50 = 16.11 ±â€¯2.29 µM). Moreover, TB-01 showed better cytotoxic than positive drug cisplatin (DDP) on tumor cells. Besides, the Zebrafish toxicity evaluation test showed that TB-01 demonstrated high biosafety. Subsequently, fluorescent staining, apoptosis detection and cell cycle analysis indicated that TB-01 induced early apoptosis in HepG2 cells and blocked the cell cycle in the G1 phase. In addition, the structure-activity relationships of these derivatives were briefly discussed.


Assuntos
Aminoácidos/farmacologia , Antineoplásicos/farmacologia , Dipeptídeos/farmacologia , Desenho de Drogas , Pirazinas/farmacologia , Triterpenos/farmacologia , Aminoácidos/química , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Dipeptídeos/química , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Humanos , Masculino , Estrutura Molecular , Pirazinas/química , Relação Estrutura-Atividade , Triterpenos/química , Peixe-Zebra
7.
J Proteomics ; 210: 103438, 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31271902

RESUMO

Sperm motility is crucial for ram fertility; however, differences in the proteome of sperm with high- and low- motility in rams (Ovis aries) has yet to be achieved. Thus, the aim of this study was to identify and characterize ram spermatozoa proteins with different abundances between high- and low- motility, and identify of proteomic markers for ram spermatozoa motility using tandem mass tag (TMT) protein labeling and LC-MS/MS. In this study, the abundance of 150 proteins in high-motility (HM) ram sperm was significantly different compared with low-motility (LM) sperm. Proteins involved in sperm motility, mitochondrial activity, and spermatogenesis showed higher abundance in HM ram spermatozoa; proteins involved in protein processing and spliceosome were more abundant in LM ram spermatozoa. In conclusion, Phosphatidylethanolamine binding protein 4 is a potential proteomic marker for ram sperm motility; CCTs/HSPs are hallmarks of the LM spermatozoa in rams. Our findings highlight the functional differences between HM and LM ejaculated spermatozoa and has identified candidate proteins of interest linked to sperm motility in rams. SIGNIFICANCE: Inadequate sperm motility is one of the most important reasons for male subfertility or infertility. In this study, we found that the abundance of 150 proteins in high-motility ram sperm was significantly different compared with low-motility sperm. Proteomic biomarkers were discovered to reflect the motility variation in ram spermatozoa; these biomarkers may assist in illuminating the molecular mechanisms underlying sperm motility. This study expands the potential direction for sperm quality screening and animal breeding.

8.
Artigo em Inglês | MEDLINE | ID: mdl-31824933

RESUMO

Wedelolactone (WED) is commonly used for the treatment of doxorubicin (DOX)-induced kidney damage, but its efficacy is limited by its poor solubility and bioavailability. In this study, we developed a novel delivery system of WED-loaded micelles (WED-M) with Solutol® HS15 and lecithin at an optimized ratio of 7:3 to improve the poor permeability and bioavailability of WED and to enhance its efficacy. The spherically shaped WED-M (particle size: 160.5 ± 3.4 nm; zeta potential: -30.1 ± 0.9 mV; entrapment efficiency: 94.41 ± 1.64%; drug loading: 8.58 ± 0.25%; solubility: 1.89 ± 0.06 mg/ml) has continuous stability over 14 days and a sustained release profile. The permeability of WED-M in Caco-2 cells indicated a significant 1.61-fold higher Papp AP to BL ratio than WED alone. Additionally, pharmacokinetic evaluation of WED-M demonstrated that the bioavailability of WED was increased 2.78-fold. Both HE staining and transmission electron microscopy showed an obvious improvement of pathological damage in WED-M treatment. Moreover, WED-M significantly enhanced the ROS level in mice and MPC5 podocytes. We concluded that using this micelle delivery system for WED could improve its permeability and bioavailability to attenuate DOX-induced oxidative injury in podocytes. This study provided important information on the fact that the micelle delivery system, WED-M, showed a significant improvement of renal damage.

9.
Brachytherapy ; 2019 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-31837988

RESUMO

PURPOSE: The aim of the study was to compare the dose distributions of combined intracavitary and interstitial (IC/IS) brachytherapy with 3-catheter IC brachytherapy in treating locally advanced (stage IIB) cervical cancer. METHODS AND MATERIALS: In total, 46 patients were included, each with stage IIB cervical cancer, local lesion sizes ≥5 cm, and tumors that had not regressed after 45 Gy/25 F external intensity-modulated radiotherapy. To identify the dosimetric advantage of delivering a local boost to high-risk (HR)-cervix in IC/IS, patients were divided into two groups: IC/IS and IC/IS + HR-cervix. The differences in dosimetric parameters were compared between the two groups. Comparisons were then made between the parameters of the four planning methods: IC (Point A), IC (three dimensional [3D]), IC/IS, and IC/IS + HR-cervix. RESULTS: In patients with IC/IS implants, the relative uterine tandem dwell time was significantly extended in the IC/IS + HR-cervix group, and the V150 and V200 volumes of HR-cervix were increased (all p < 0.001), whereas the D90 and D100 values of the IC/IS + HR-cervix group were lower than those in the IC/IS group. In pairwise comparisons, HR-cervix V150 and V200 values were lowest in the IC/IS group, followed by the IC (3D), IC/IS + HR-cervix, and IC (Point A) groups. All differences were statistically significant (p < 0.05), with the exception of IC/IS vs. IC (3D). CONCLUSIONS: When treating locally advanced cervical cancer (stage IIB, local residual volume ≥5 cm after external radiotherapy), the IC/IS + HR-cervix optimization method can meet the HR clinical target volume D90 dose requirement, normal tissue dose limits, and can escalate doses to local areas of the cervix.

11.
Zhongguo Dang Dai Er Ke Za Zhi ; 21(12): 1198-1202, 2019 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-31874659

RESUMO

OBJECTIVE: To study the value of serum gamma-glutamyl transpeptidase (GGT) combined with direct bilirubin (DB) in the diagnosis of biliary atresia. METHODS: A total of 667 infants with cholestasis who were hospitalized and treated from July 2010 to December 2018 were enrolled as subjects. According to the results of intraoperative cholangiography and follow-up, they were divided into biliary atresia group with 234 infants and cholestasis group with 433 infants. The two groups were compared in terms of age of onset, sex, and serum levels of total bilirubin (TB), DB, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bile acid (TBA), and GGT. A receiver operating characteristic (ROC) curve analysis was performed for indices with statistical significance, and the area under the ROC curve (AUC) and the optimal cut-off value for diagnosis were calculated. RESULTS: The biliary atresia group had a significantly younger age of onset than the cholestasis group (P<0.001). There were no significant differences in sex, ALT, and AST between the two groups (P>0.05), while the biliary atresia group had significantly higher serum levels of TB, DB, TBA, and GGT than the cholestasis group (P<0.05). GGT combined with DB had the highest AUC of 0.892 (95% confidence interval: 0.868-0.916) in the diagnosis of biliary atresia. At the optimal cut-off values of 324.0 U/L for GGT and 115.1 µmmol/L for DB, GGT combined with DB had a sensitivity of 79.8% and a specificity of 83.2% in the diagnosis of biliary atresia. CONCLUSIONS: GGT combined with DB has high sensitivity and specificity in the diagnosis of biliary atresia and can be used as an effective indicator for diagnosis of biliary atresia in infants.


Assuntos
Atresia Biliar , gama-Glutamiltransferase/sangue , Alanina Transaminase , Aspartato Aminotransferases , Atresia Biliar/diagnóstico , Bilirrubina , Humanos , Lactente
12.
SLAS Discov ; : 2472555219894543, 2019 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-31858876

RESUMO

Atherosclerosis is the pathological basis of most cardiovascular diseases. Reverse cholesterol transport (RCT) is a main mechanism of cholesterol homeostasis and involves the direct transport of high-density lipoprotein (HDL) cholesteryl ester by selective cholesterol uptake. Hepatic scavenger receptor class B member 1 (SR-BI) overexpression can effectively promote RCT and reduce atherosclerosis. SR-BI may be an important target for prevention or treatment of atherosclerotic disease. In our study, we inserted human SR-BI mRNA 3' untranslated region (3'UTR) downstream of the luciferase reporter gene, to establish a high-throughput screening model based on stably transfected HepG2 cells and to screen small-molecule compounds that can significantly enhance the mRNA stability of the SR-BI gene. Through multiple screenings of 25 755 compounds, the top five active compounds that have similar structures were obtained, with a positive rate of 0.19%. The five positive compounds could enhance the SR-BI expression and uptake of DiI-HDL in the hepatocyte HepG2. E238B-63 could also effectively extend the half-life of SR-BI mRNA and enhance the SR-BI mRNA and protein level and the uptake of DiI-HDL in hepatocytes in a time-dependent and dose-dependent manner. The structure-activity relationship analysis showed that the structure N-(3-hydroxy-2-pyridyl) carboxamide is possibly the key pharmacophore of the active compound, providing reference for acquiring candidate compounds with better activity. The positive small molecular compounds obtained in this study might become new drug candidates or lead compounds for the treatment of cardiovascular diseases and contribute to the further study of the posttranscriptional regulation mechanism of the SR-BI gene.

13.
Nan Fang Yi Ke Da Xue Xue Bao ; 39(11): 1320-1328, 2019 Nov 30.
Artigo em Chinês | MEDLINE | ID: mdl-31852651

RESUMO

OBJECTIVE: Sparse-view CT has the advantages of accelerated data collection and reduced radiation dose, but data missing arising from the data collection process causes serious streaking artifact and noise in the images reconstructed using the traditional filtering back projection algorithm (FBP). To solve this problem, we propose a multi-scale wavelet residual network (MWResNet) to restore sparse-view CT images. METHODS: The MWResNet was based on the combination of deep learning and traditional model in MWCNN, and the wavelet network was combined with the residual block to enhance the network's ability to embed image features and speed up network training. The network proposed herein was trained using the real spiral geometry CT image data, namely the Low-dose CT Grand Challenge dataset. The results of the proposed networks were visually and quantitatively compared to that by other existing networks, including the image restoration iterative residual convolution network (IRLNet), residual coding-decoding convolutional neural network (REDCNN) and the FBP convolutional neural network (FBPConvNet). RESULTS: The results demonstrated that the proposed method was superior to other competing methods in terms of visual inspection and quantitative comparison. CONCLUSIONS: The MWResNet network is an effective method for suppressing noise and artifacts and maintaining edges details in the sparse-view CT images.


Assuntos
Tomografia Computadorizada por Raios X , Algoritmos , Artefatos , Processamento de Imagem Assistida por Computador
14.
Food Sci Nutr ; 7(11): 3731-3741, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31763022

RESUMO

Canolol is a potential antioxidation ingredient in rapeseed oil. Rapeseed oil with two levels of canolol (528.9 vs. 250.5 mg/kg) was used for stir-frying different foods (potatoes, tofu, and vegetables). Comprehensive evaluations indicated that the canolol content in high canolol rapeseed oil (HCR) and low canolol rapeseed oil (LCR) after stir-frying were in the range of 187.8-237.7 and 45.6-96.4 mg/kg, respectively. The degradation rate of total phenol was 58.4% and 80.3% in HCR and LCR, respectively. The loss rates of α- and γ-tocopherol were 24.5% and 47.6%, respectively. Phytosterol concentration decreased by 20% and trans-fatty acid was not detected in either rapeseed oil. In addition, the peroxide value, anisidine value, and malondialdehyde content in HCR were lower than those in LCR. The oxidative stability index in HCR was longer, showing lower extent of deterioration. Rapeseed oil with high canolol content displayed good oxidation resistance due to significant positive correlation with oxidation induction time (p < .01).

15.
EBioMedicine ; 49: 232-246, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31680002

RESUMO

BACKGROUND: Hepatitis B surface antigen (HBsAg) is one of the important clinical indexes for hepatitis B virus (HBV) infection diagnosis and sustained seroconversion of HBsAg is an indicator for functional cure. However, the level of HBsAg could not be reduced by interferons and nucleoside analogs effectively. Therefore, identification of a new drug targeting HBsAg is urgently needed. METHODS: In this study, 6-AN was screened out from 1500 compounds due to its low cytotoxicity and high antiviral activity. The effect of 6-AN on HBV was examined in HepAD38, HepG2-NTCP and PHHs cells. In addition, the antivirus effect of 6-AN was also identified in mouse model. FINDINGS: 6-AN treatment resulted in a significant decrease of HBsAg and other viral markers both in vitro and in vivo. Furthermore, we found that 6-AN inhibited the activities of HBV SpI, SpII and core promoter by decreasing transcription factor PPARα, subsequently reduced HBV RNAs transcription and HBsAg production. INTERPRETATION: We have identified a novel small molecule to inhibit HBV core DNA, HBV RNAs, HBsAg production, as well as cccDNA to a minor degree both in vitro and in vivo. This study may shed light on the development of a novel class of anti-HBV agent.

16.
Sci Rep ; 9(1): 16345, 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31705023

RESUMO

Scalable superconducting nanowire single photon detector (SNSPDs) arrays require cryogenic digital circuits for multiplexing the output detection pulses. Among existing superconducting digital devices, superconducting nanowire cryotron (nTron) is a three-terminal device with an ultra-compact size, which is promising for large scale monolithic integration. In this report, in order to evaluate the potential and possibility of using nTrons for reading and digitizing SNSPD signals, we characterized the grey zone, speed, timing jitter and power dissipation of a proper designed nTron. With a DC bias on the gate, the nTron can be triggered by a few µA high and nanoseconds wide input signal, showing the nTron was capable of reading an SNSPD pulse at the same signal level. The timing jitter depended on the input signal level. For a 20 µA high and 5 ns wide input pulse, the timing jitter was 33.3 ps, while a typical SNSPD's jitter was around 50 ps. With removing the serial inductors and operating it in an AC bias mode. The nTron was demonstrated to be operated at a clock frequency of 615.4 MHz, which was faster than the maximum counting rate of a typical SNSPD. In additional, with a 50 Ω bias resistor and biased at 17.6 µA, the nTron had a total power dissipation of 19.7 nW. Although RSFQ circuits are faster than nTrons, for reading SNSPD or other detector arrays that demands less operation speed, our results suggest a digital circuit made from nTrons could be another promising alternative.

17.
J Mol Neurosci ; 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31732924

RESUMO

Delayed neurologic sequelae (DNS) are among the most serious complications of carbon monoxide (CO) poisoning caused partly by elevated neuroinflammation. WIN 55,212-2, a non-selective agonist of cannabinoid receptors, has been demonstrated to have anti-inflammatory properties in various brain disorders. The anti-inflammatory action of WIN 55,212-2 is potentially associated with driving microglial M2 polarization. ST2 signaling is important in regulating inflammatory responses and microglial polarization. Therefore, we aimed to investigate the neuroprotective effect of WIN 55,212-2 on DNS after CO poisoning and elucidate its relationship with ST2-mediated microglial M2 polarization. The behavioral tests showed that treatment with WIN 55,212-2 significantly ameliorates the cognitive impairment induced by CO poisoning. This behavioral improvement was accompanied by reduced neuron loss, decreased production of pro-inflammatory cytokines, and a limited number of microglia in the hippocampus. Moreover, WIN 55,212-2 elevated the protein expression of IL-33 (the ligand of ST2) and ST2, increased the ratio of CD206-positive (M2 phenotype) and ST2-positive microglia, and augmented production of M2 microglia-associated cytokines in the hippocampus of CO-exposed rats. Furthermore, we observed that the WIN 55,212-2-mediated increases in ST2 protein expression, CD206-positive and ST2-positive microglia, and microglia-associated cytokines were blocked by the cannabinoid receptor 2 (CB2R) antagonist AM630 but not by the cannabinoid receptor 1 (CB1R) antagonist AM251. In contrast, the WIN 55,212-2-induced upregulation of the IL-33 protein expression was inhibited by AM251 but not by AM630. Altogether, these findings reveal cannabinoid receptors as promising therapeutic agents for CO poisoning and identify ST2 signaling-related microglial M2 polarization as a new mechanism of cannabinoid-induced neuroprotection.

18.
J Asian Nat Prod Res ; : 1-7, 2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31738087

RESUMO

Bistachybotrysin K (1), one new phenylspirodrimane dimer with a central 6/7 oxygen heterocycle core, was isolated from the fungus Stachybotrys chartarum CGMCC 3.5365. Its structure was elucidated by extensive spectroscopic data and single-crystal X-ray diffraction. Compound 1 showed significant cytotoxicity against human tumor cell lines HCT116, NCI-H460, BGC823, Daoy, and HepG2 with IC50 values in the range of 1.1-4.7 µM.

19.
Sheng Li Xue Bao ; 71(5): 681-688, 2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31646321

RESUMO

Polyamines (putrescine, spermidine, and spermine) are essential polycations that play important roles in various physiological and pathophysiological processes in mammalian cells. The study was to investigate their role in cardioprotection against ischemia/reperfusion (I/R) injury and the underlying mechanism. Isolated hearts from male Sprague-Dawley rats were Langendorff-perfused and cardiac I/R was achieved by 30 min of global ischemia followed by 120 min of reperfusion. Different concentrations of polyamines (0.1, 1, 10, and 15 µmol/L of putrescine, spermidine, and spermine), cyclosporin A (0.2 µmol/L), or atractyloside (20 µmol/L) were given 10 min before the onset of reperfusion. The hemodynamics were monitored; the lactate dehydrogenase (LDH) levels in the coronary effluent were measured spectrophotometrically; infarct size was determined by the 2,3,5-triphenyltetrazolium chloride staining method; and mitochondrial permeability transition pore (MPTP) opening was determined spectrophotometrically by the Ca2+-induced swelling of isolated cardiac mitochondria. The results showed that compared to I/R alone, 0.1 and 1 µmol/L polyamines treatment improved heart function, reduced LDH release, decreased infarct size, and these effects were inhibited by atractyloside (MPTP activator). In isolated mitochondria from normal rats, 0.1 and 1 µmol/L polyamines treatment inhibited MPTP opening. However, 10 and 15 µmol/L polyamines treatment had the opposite effects, and these effects were inhibited by cyclosporin A (MPTP inhibitor). Our findings showed that polyamines may have either protective or damaging effects on hearts suffering from I/R by inhibiting or activating MPTP opening.


Assuntos
Proteínas de Transporte da Membrana Mitocondrial/fisiologia , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Poliaminas/metabolismo , Animais , Ciclosporina/farmacologia , Masculino , Mitocôndrias Cardíacas/fisiologia , Ratos , Ratos Sprague-Dawley
20.
Cell Cycle ; 18(21): 2860-2875, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31599708

RESUMO

Malignant melanoma has a profound influence on populations around the world, with the underlying mechanisms controlling this disease yet to be fully identified. Hence, the current study aimed to investigate effects associated with VEPH1 on epithelial-mesenchymal transition (EMT), proliferation, invasion, migration and the apoptosis of human cutaneous melanoma (CM) cells through the TGF-ß signaling pathway. Microarray-based gene analysis was initially performed to screen the CM-related differentially expressed genes. The expression of VEPH1, TGF-ß signaling pathway- and EMT-related genes in CM tissues and cell lines was subsequently evaluated. Gain-of- and loss-of-function experiments were conducted to examine the effects of VEPH1 and the TGF-ß signaling pathway on the expression of EMT-related genes, cell proliferation, migration, invasion, cell cycle and apoptosis in vitro. Finally, tumor formation in nude mice was conducted. VEPH1 was lowly expressed and regulated the progression of CM with involvement in the TGF-ß signaling pathway. Human CM tissues were noted to activate the TGF-ß signaling pathway and EMT. A375 cells treated with overexpressed VEPH1 plasmids or/and TGF-ß signaling pathway inhibitor SB-431542 displayed diminished TGF-ß, SMAD4, Vimentin and N-cadherin expression while the expression of E-cadherin was elevated, accompanied by decreased cell proliferation, migration, invasion, inhibited cell cycle entry. However, si-VEPH1 or TGF-ß signaling pathway activator contributed to reverse results. Taken together, the key findings of the current study present evidence suggesting that VEPH1 protects against human CM by inhibiting the activation of the TGF-ß signaling pathway, highlighting its potential as a target for the prognosis and diagnosis of CM.

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