Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 328
Filtrar
2.
J Cardiovasc Pharmacol ; 77(2): 142-152, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33538531

RESUMO

ABSTRACT: Isoprenylation is an important post-transcriptional modification of small GTPases required for their activation and function. Isoprenoids, including farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate, are indispensable for isoprenylation by serving as donors of a prenyl moiety to small G proteins. In the human body, isoprenoids are mainly generated by the mevalonate pathway (also known as the cholesterol-synthesis pathway). The hydroxymethylglutaryl coenzyme A reductase catalyzes the first rate-limiting steps of the mevalonate pathway, and its inhibitor (statins) are widely used as lipid-lowering agents. In addition, the FPP synthase is also of critical importance for the regulation of the isoprenoids production, for which the inhibitor is mainly used in the treatment of osteoporosis. Synthetic FPP can be further used to generate geranylgeranyl pyrophosphate and cholesterol. Recent studies suggest a role for isoprenoids in the genesis and development of cardiovascular disorders, such as pathological cardiac hypertrophy, fibrosis, endothelial dysfunction, and fibrotic responses of smooth-muscle cells. Furthermore, statins and FPP synthase inhibitors have also been applied for the management of heart failure and other cardiovascular diseases rather than their clinical use for hyperlipidemia or bone diseases. In this review, we focus on the function of several critical enzymes, including hydroxymethylglutaryl coenzyme A reductase, FPP synthase, farnesyltransferase, and geranylgeranyltransferase in the mevalonate pathway which are involved in regulating the generation of isoprenoids and isoprenylation of small GTPases, and their pathophysiological role in the cardiovascular system. Moreover, we summarize recent research into applications of statins and the FPP synthase inhibitors to treat cardiovascular diseases, rather than for their traditional indications respectively.

3.
Phys Chem Chem Phys ; 2021 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-33595560

RESUMO

The structural, electronic and magnetic properties of the T-phase and H-phase of the VS2 monolayer and their heterobilayers are studied by means of first-principles calculations. We find that the two phases of the VS2 monolayer are both ferromagnetic (FM) semiconductors and that these two monolayers form a typical van der Waals (vdW) heterostructure with a weak interlayer interaction. By comparing the energy of different magnetic configurations, the FM state of the tVS2/hVS2 heterostructure is found to be in the ground state under normal conditions or biaxial strains. Under compressive strains, the anti-FM (AFM) and FM states degenerate. Based on the band structure obtained and the work function, it is found that the T-phase and H-phase are capable of forming an efficient p-n heterostructure. Due to spontaneous charge transfer at the interface, a gapless semiconductor is formed in our HSE06 calculations. We also find that the twist angle between the monolayers has a negligible impact on the band structure of the heterostructure in its spin-down channel. Moreover, the tVS2/hVS2 heterostructure is found to switch from a gapless semiconductor to a metal or a half-metal under some given biaxial or uniaxial strains. Therefore, the heterostructure could be a half-metallic property with strains, realizing 100% polarization at the Fermi level. Our study provides the possibility of realizing 100% spin-polarization at the Fermi level in these FM vdW heterostructures, which is significant for further spin transport exploration.

4.
Oncol Rep ; 45(1): 408, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33416151

RESUMO

An interested reader drew to our attention that the western blots featured in Figs. 1B and 6C contained strikingly similar protein bands, and repeating patterns of bands, comparing across the lanes of the gels. Furthermore, an image representing the Myc­YAP colony­formation assay experiment in Fig. 2C was strikingly similar to the data shown for the Control colony­formation assay experiment in Fig. 5B. The Editorial office subsequently investigated this matter further, and noted that the western blots shown in Fig. 6A and B likewise contained strikingly similar bands that were purportedly showing the results from different experiments. After having considered the various issues that have been brought to light with this paper, together with an appeal from the authors that a Corrigendum be published, the Editor of Oncology Reports has ruled that the article should be retracted from the publication on account of a lack of overall confidence in the presented data. Note that the authors were not in agreement that the errors reported and identified were sufficient to merit the retraction of the article. The Editor apologizes to the readership for any inconvenience caused. [the original article was published in Oncology Reports 40: 609-620, 2018; DOI: 10.3892/or.2018.6486].

5.
J Appl Clin Med Phys ; 22(2): 158-164, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33369106

RESUMO

PURPOSE: To investigate the diagnostic value and feasibility of radiomics-based texture analysis in differentiating pulmonary sclerosing pneumocytoma (PSP) from solid malignant pulmonary nodules (SMPN) on single- and three-phase computed tomography (CT) images. MATERIALS AND METHODS: A total of 25 PSP patients and 35 SMPN patients with pathologically confirmed results were retrospectively included in this study. For each patient, the tumor regions were manually labeled in images acquired at the noncontrast phase (NCP), arterial phase (AP), and venous phase (VP). The least absolute shrinkage and selection operator (LASSO) method was used to select the most useful predictive features extracted from the CT images. The predictive models that discriminate PSP from SMPN based on single-phase CT images (NCP, AP, and VP) or three-phase CT images (Combined model) were developed and validated through fivefold cross-validation using a logistic regression classifier. Model performance was evaluated using receiver operating characteristic (ROC) analysis. The predictive performance was also compared between the Combined model and human readers. RESULTS: Four, five, and five features were selected from NCP, AP, and VP CT images for the development of radiomic models, respectively. The NCP, AP, and VP models exhibited areas under the curve (AUCs) of 0.748 (95% confidence interval [CI], 0.620-0.852), 0.749 (95% CI, 0.620-0.852), and 0.790 (95% CI, 0.665-0.884) in the validation dataset, respectively. The Combined model based on three-phase CT images outperformed the NCP, AP, and VP models (all p < 0.05), yielding an AUC of 0.882 (95% CI, 0.773-0.951) in the validation dataset. The Combined model displayed noninferior performance compared to two senior radiologists; however, it outperformed two junior radiologists (p = 0.004 and 0.001, respectively). CONCLUSION: The Combined model based on radiomic features extracted from three-phase CT images achieved radiologist-level performance and could be used as promising noninvasive tool to differentiate PSP from SMPN.

6.
Artigo em Inglês | MEDLINE | ID: mdl-33224259

RESUMO

Rosanortriterpenes A-B (RTA and RTB), two nortriterpenoids, are characteristic constituents in the fruits of Rosa laevigata var. leiocapus. However, pharmacological studies on these compounds are still scarce. In the present study, we aim to investigate the anti-inflammatory mechanisms associated with the effects of RTA-B in RAW264.7 macrophages and LO2 cells by detecting cell viabilities, nitric oxide (NO) production, tumour necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) production. Simultaneously, the anti-inflammatory action mechanisms of these two compounds were illustrated through western blot assay. Besides, the antihepatic fibrosis activities of these compounds have also been explored. The results demonstrated that RTA and RTB inhibited the production of NO, TNF-α, and IL-6 and suppressed liver fibrosis. RTA and RTB treatment also greatly inhibited the activation of NF-kappaB (NF-κB) pathway. Our study confirmed the promising anti-inflammatory and anti-liver fibrosis actions of RTA-B, suggesting that they might be developed as alternative and promising drugs for the treatment of hepatic inflammatory and fibrotic diseases.

7.
Oncol Rep ; 2020 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-33169798

RESUMO

Following the publication of this paper, it was drawn to the authors' attention by an interested reader that Fig. 6D contained images featuring overlapping data, which reportedly had been derived under different experimental conditions. Subsequently, further issues of data duplication were brought to light by another interested reader concerning the above article; first, certain of the images showing colony­forming assays in Fig. 4D were strikingly similar to images that had appeared in a previous publication by the same research group, and secondly, a couple of instances of data duplication were identified among the histopathological images presented within Fig. 7D. After having considered the various issues that have been brought to light with this paper, together with an appeal from the authors that a Corrigendum be published, the Editor of Oncology Reports has ruled that the article should be retracted from the publication on account of a lack of overall confidence in the presented data. Note that the authors were not in agreement that the number of errors reported and identified were sufficient to merit the retraction of the article. Additionally, the authors carefully checked the raw data and drew a conclusion that the final scientific conclusions were not affected. The Editor and the authors apologize to the readership for any inconvenience caused. [the original article was published in Oncology Reports 39: 2114­2126, 2018; DOI: 10.3892/or.2018.6297].

8.
Plant Biotechnol J ; 2020 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-33217142

RESUMO

Increasing the targeting ability of antifungal proteins towards specific components of fungal cells has the potential to improve their antifungal activity and reduce harmful effects to nontarget cells. To obtain effective disease resistance genes against cotton Verticillium wilt, we constructed several fusion genes, in which binding domains targeting chitin, sphingolipid or ergosterol in the fungal cell wall or cell membrane were individually fused to the antifungal peptide BbAFP1 from entomopathogenic fungus Beauveria bassiana. Transient expression of fusion genes in cotton cotyledons indicated that the BbAFP1::ErBD fusion peptide with an ergosterol binding domain exhibited better disease resistance against V. dahliae than wild-type BbAFP1 and other fusion genes. BbAFP1::ErBD and BbAFP1 transgenic cotton were obtained and verified by Southern and Western blotting. Compared with BbAFP1-expressing cotton, BbAFP1::ErBD-expressing cotton showed higher disease resistance against V. dahliae, with smaller lesion areas (0.07 cm2 vs. 0.16 cm2 ) on the leaves and a lower disease index (23.9 vs. 34.5). Overexpression of BbAFP1::ErBD by transgenic tobacco also showed enhanced disease resistance against V. dahliae compared with that of the wild-type gene. These results indicated that construction of fusion antifungal peptides that target fungal cells is a powerful strategy to obtain new anti-disease genes, and the obtained fusion gene BbAFP1::ErBD has the potential to defend against plant fungal diseases.

9.
Bioorg Med Chem ; : 115849, 2020 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-33221063

RESUMO

Neothalfine is a natural bisbenzylisoquinoline alkaloid with the abundant resource in medicinal plants and has not been reported its anti-tumor efficacy. In the present study, the anti-tumor efficacy was investigated and it showed broad-spectrum activity against several cancer cell lines, especially metastatic colorectal cancer (HCT116, SW620, T84) with the IC50 values of 7.2, 5.9, 8.2 nM, respectively, roughly equal to well-known anti-tumor agent docetaxel (4.0, 4.7, 2.7 nM) and nearly 1000 folds than CPT-11 (4.4, 5.1, 6.9 µM). Furthermore, neothalfine inhibited colorectal cell proliferation by resulting in cell cycle arrest at the G2/M phase and induced apoptosis through the dysfunction of mitochondria to trigger intrinsic apoptotic pathway by untargeted metabolomic method, mitochondrial membrane potential, and caspase-3/7 activity assay. Moreover, neothalfine damaged colorectal cancer clonal spheres expansion significantly at the concentration of 3.5 nM with nearly 1000 folds efficacy than CPT-11 (3.0 µM). The results supported that neothalfine might be an anti-tumor lead for further investigation.

10.
J Ethnopharmacol ; : 113552, 2020 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-33152431

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Sapindus mukorossi Gaertn. (S. mukorossi), known as 'mu huan zi' in Chinese folklore, belongs to the family Sapindaceae and it has been traditionally used for treating coughing and excessive salivation, removing freckle, whitening skin, etc. Evidence-based medicine also verified the antimicrobial, anti-tyrosinase and anti-acne activity of S. mukorossi extract, suggesting that it has the potential to be a pharmaceutical and cosmetic additive. AIM OF THE STUDY: The present study was intended to evaluate the freckle-removing and skin-whitening activities of S. mukorossi extracts, and further analyzing the potential anti-acne mechanism. METHODS: Saponin fractions were purified by using the semi-preparative high-performance liquid chromatography, and their antibacterial activity was detected against Propionibacterium acnes (P. acnes), which was the leading cause of inflamed lesions in acne vulgaris. The anti-lipase and anti-tyrosinase activities were assayed using a commercial kit, while the potential anti-acne mechanism was predicted on the basis of the network pharmacology. Active components of saponin fraction were identified by HPLC-MS analysis. Furthermore, the different toxicity level of compounds was predicted according to the quantitative structure-activity relationship, and the first application of crude extract and saponin fraction to facial masks was analyzed based on the comprehensive evaluation method. RESULTS: The saponin fraction (F4) purified from the fermentation liquid-based water extract (SWF) showed the best antibacterial activity against P. acnes ATCC 6919 with the MIC of 0.06 mg/mL, which was 33-fold of its parent SWF (with the MIC of 2.0 mg/mL). Compared with SWF, the application of F4 caused greater inhibition rates on lipase and tyrosinase. Chemical constituents of F4 were evaluated, from which four oleanane-type triterpenoid saponins were detected to contribute to the above biological activities of F4. The mechanism of the four compounds on anti-acne was predicted, and seven targets such as PTGS2 and F2RL1 were obtained to be important for the treatment of acne. The four compounds were also predicted to have different levels of toxicity to various species, and they were not harmful to rats. Besides, F4 and SWF were applied to facial masks and there was no significant influence on the physicochemical properties including pH, stability, and sensory characteristics. CONCLUSION: This work demonstrated that oleanane-type triterpenoid saponins were speculated to contribute to the skin-whitening, freckle-removing, and anti-acne activities of F4. These findings will facilitate the development of the S. mukorossi extract and the allied products as the new and natural anti-acne agent and cosmetic additives.

11.
Food Funct ; 2020 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-33210684

RESUMO

Type 2 diabetes has a series of metabolic aberrations accompanied by chronic hyperglycemia, along with various comorbidities. In recent reports, punicalagin from pomegranate has been reported to exert hypoglycemic effects against diabetes. The goal of the current research was to investigate the therapeutic effectiveness and elucidate the mechanisms of punicalagin underlying type 2 diabetes. Type 2 diabetes was induced by a high-fat diet (HFD) combined with streptozotocin (STZ) injection in C57BL/6J mice. Punicalagin was administered daily by oral gavage for 4 weeks. The results indicated that high FBG (fasting blood glucose), dyslipidemia and associated islet, liver and kidney injury were observed in the model group mice. Through metabolomics analysis, it was found that the administration of punicalagin could regulate 24 potential biomarkers and their related metabolic pathways. Moreover, the pathological changes in the liver and kidney were mainly mediated by reducing gluconeogenesis and increasing glycogenesis via stimulation of the PI3K/AKT signaling pathway and regulation of the HMGB-1/TLR4/NF-κB signaling pathway, which simultaneously interrelated to ten main pathological pathways. In addition, we confirmed the positive role of punicalagin in glucosamine-induced HepG2 cells and HG-induced HK-2 cells through related mechanistic studies in vitro. In conclusion, these findings suggested that the multi-effect and multi-target action mode of punicalagin had a significant hypoglycemic effect and a protective effect on diabetes mellitus. Punicalagin might serve as an alternative functional food or as a clinical supplemental therapy for the diabetic population to ameliorate metabolic syndrome.

12.
Nat Prod Res ; : 1-7, 2020 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-33131334

RESUMO

Two new compounds (1 and 2), belonging to C-20 oxygenated ent-kauranes-type diterpenoids, were identified from the aerial parts of Isodon serra. Their structures were elucidated by extensive analysis of HRESI-MS and NMR spectroscopic data. Both these two compounds possess a common 7,20-epoxy-ent-kauranes skeleton with a hydroxyl group rarely occurring at C-13. Compounds 1 and 2 were evaluated for their cytotoxic activity against Hela-60 and HepG2 as well as the antibacterial activity against Staphylococcus aureus, Bacillus cereus and Escherichia coli.

13.
J Oncol ; 2020: 5025641, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33133187

RESUMO

[This corrects the article DOI: 10.1155/2019/8607859.].

14.
Plast Reconstr Surg ; 146(6): 1275-1284, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33234957

RESUMO

BACKGROUND: The stromal vascular fraction can improve volume retention after fat grafting, but the optimal stromal vascular fraction extraction method remains controversial. This study investigated the effect of mechanical vibration on stromal vascular fraction activity and explored the efficacy of vibration as a new extraction method compared to centrifugation, enzyme digestion, and nanoemulsion methods. METHODS: Twenty-four rabbits were divided into three groups, and adipose tissue was harvested from the scapular region of each rabbit. In the first group, stromal vascular fraction was extracted from adipose tissue by vibration with different frequencies and durations. Cell counts and colony formation were assessed to determine the optimal vibration parameters. In the second group, stromal vascular fraction was extracted by the four methods, and the cell counts, proliferation, and adipogenic capabilities were observed in vitro. In the third group, adipose tissue mixed with stromal vascular fraction extracted by means of the four methods was grafted into rabbit ears. Volume retention and histologic changes were evaluated over 24 weeks. RESULTS: Stromal vascular fraction activity was not influenced by low-frequency (≤45 Hz) and short-duration (≤20 minutes) vibrations. Vibration at 30 Hz for 15 minutes was most efficient for stromal vascular fraction extraction. In vitro, stromal vascular fraction extracted by vibration showed advantages for cell viability. In vivo, the vibration group showed a more normal tissue morphology and a higher retention rate (60.68 ± 7.07 percent) than the enzyme digestion (31.88 ± 4.99 percent), centrifugation (43.76 ± 4.32 percent), and nanoemulsion groups (21.79 ± 3.57 percent) (p < 0.05). CONCLUSION: Vibration at 30 Hz for 15 minutes is recommended as a novel nonenzymatic method to extract stromal vascular fraction with high activity.

15.
Environ Toxicol ; 2020 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-33236476

RESUMO

Panax ginseng, a functional food, has been widely used as an edible nourishment and medicinal supplement. Ginsenoside Rb1 is a major bioactive ingredient of ginseng, which shows very specific anti-apoptosis and anti-oxidant activities. Methylglyoxal (MGO) is one of intermediate products of glucose metabolism, which is absorbed easily from high sugar foods or carbonated beverages. It may involve in a variety of detrimental processes in vivo. However, it has not been fully explored the effects of ginsenoside Rb1 on MGO-induced oocytes damage. This study found that MGO-induced DNA damage and mitochondrial dysfunction result in the failure of porcine oocytes maturation and low in vitro development capacity of parthenogenetic activation (PA) and in vitro fertilization (IVF) embryos. Conversely, Rb1 supplementation recovered the rate of maturation, and improved in vitro development capacity of PA and IVF embryos. Rb1 also provided porcine oocytes a lower level of reactive oxygen species production, higher level of ATP content and mitochondrial membrane potential, and stimulated pluripotency gene expression in blastocysts. The findings of this study reveal ginsenoside Rb1 protects porcine oocyte from the cytotoxicity effects of methylglyoxal and provides novel perspectives for the protection of reproduction system by functional food of ginseng.

16.
Sensors (Basel) ; 20(22)2020 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-33238402

RESUMO

A tip-enhanced Raman spectroscopy (TERS) system based on an atomic force microscope (AFM) and radially polarized laser beam was developed. A TERS probe with plasmon resonance wavelength matching the excitation wavelength was prepared with the help of dark-field micrographs. The intrinsic photoluminescence (PL) from the silver (Ag)-coated TERS probe induced by localized surface plasmon resonance contains information about the near-field enhanced electromagnetic field intensity of the probe. Therefore, we used the intensity change of Ag PL to evaluate the stability of the Ag-coated probe during TERS experiments. Tracking the Ag PL of the TERS probe was helpful to detect probe damage and hotspot alignment. Our setup was successfully used for the TERS imaging of single-walled carbon nanotubes, which demonstrated that the Ag PL of the TERS probe is a good criterion to assist in the hotspot alignment procedure required for TERS experiments. This method lowers the risk of contamination and damage of the precious TERS probe, making it worthwhile for wide adoption in TERS experiments.

17.
Biosens Bioelectron ; 170: 112662, 2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-33032198

RESUMO

Cancer cell enumeration and phenotyping can predict the prognosis and the therapy efficacy in patients, yet it remains challenging to detect the rare tumor cells. Herein, we report an octopus-inspired, bifunctional aptamer signal amplifier-based cytosensor (OApt-cytosensor) for sensitive cell analysis. By assembling high-affinity antibodies on an electrode surface, the target cells could be specifically captured and thus been sandwiched by the cell surface marker-specific DNA aptamers. These on-cell aptamers function as electrochemical signal amplifiers by base-selective electronic doping with methylene blue. Such a sandwich configuration enables highly sensitive cell detection down to 10 cells/mL (equal to ~1-2 cells at a sampling volume of 150 µL), even in a large excess of nontarget blood cells. This approach also reveals the cell-surface markers and tracks the cellular epithelial-to-mesenchymal transition induced by signaling regulators. Furthermore, the electron-doped aptamer shows remarkable cell fluorescent labeling that guides the release of the captured cells from electrode surface via electrochemistry. These features make OApt-cytosensor a promising tool in revealing the heterogeneous cancer cells and anticancer drug screening at the single-cell level.

19.
Front Pharmacol ; 11: 1222, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32973496

RESUMO

Gallic acid (GA), a hydrolyzable tannin, has a wide range of pharmacological activities. This study revealed that, GA significantly inhibited T24 cells viability in a concentration- and time- dependent manner. The IC50 of GA stimulating T24 cells for 24, 48, and 72 h were 21.73, 18.62, and 11.59 µg/ml respectively, and the inhibition rate was significantly higher than the positive control drug selected for CCK-8 assay. Meanwhile, after GA treatment, the morphology of T24 cells were changed significantly. Moreover, GA significantly inhibited T24 cells proliferation and blocked T24 cells cycle in S phase (p < 0.001). GA induced T24 cells apoptosis (p < 0.001), accompanied by reactive oxygen species (ROS) accumulation and mitochondrial membrane potential (MMP) depolarization. Western blotting analysis showed that GA significantly increased Cleaved caspase-3, Bax, P53, and Cytochrome C (Cyt-c) proteins expression, and decreased Bcl-2, P-PI3K, P-Akt, P-IκBα, P-IKKα, and P-NF-κB p65 proteins expression in T24 cells (p < 0.05). Real-Time PCR results verified that GA significantly promoted Caspase-3, Bax, P53, and Cyt-c genes expression, and inhibited Bcl-2, PI3K, Akt, and NF-κB p65 genes expression (p < 0.001). However, on the basis of GA (IC50) stimulation, NAC (an oxidative stress inhibitor) pretreatment reversed the apoptotic rate of T24 cells and the expression of Bax, Cleaved caspase-3, P53, Bcl-2 proteins, and the MMP level in T24 cells, as well as the expression of Cyt-c protein in T24 cells mitochondria and cytoplasm. In addition, GA significantly suppressed T24 cells migration and invasion ability with VEGF protein inhibition (p < 0.001). Briefly, GA can inhibit T24 cells proliferation, metastasis and promote apoptosis, and the pro-apoptotic activity is closely associated with mitochondrial dysfunction and PI3K/Akt/NF-κB signaling suppression. Our study will help in finding a safe and effective treatment for bladder cancer.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA