Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 394
Filtrar
1.
Eur J Pharmacol ; : 173659, 2020 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-33131637

RESUMO

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the pathogen of 2019 novel coronavirus disease (COVID-19), is currently spreading around the world. The WHO declared on January 31 that the outbreak of SARS-CoV-2 was a public health emergency. SARS-Cov-2 is a member of highly pathogenic coronavirus group that also consists of severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East Respiratory Syndrome Coronavirus (MERS-CoV). Although respiratory tract lesions were regarded as main manifestation of SARS-Cov-2 infection, gastrointestinal lesions were also reported. Similarly, patients with SARS-CoV and MERS-CoV were also observed. Common gastrointestinal symptoms of patients mainly included diarrhea, vomiting and abdominal pain. Gastrointestinal lesions could be used as basis for early diagnosis of patients, and at the same time, controlling gastrointestinal lesions better facilitated to cut off the route of fecal-oral transmission. Hence, this review summarizes the characteristics and mechanism of gastrointestinal lesions caused by three highly pathogenic human coronavirus infections including SARS-CoV, MERS-CoV, as well as SARS-CoV-2. Furthermore, it is expected to gain experience from gastrointestinal lesions caused by SARS-CoV and MERS-CoV infections in order to be able to better relieve SARS-CoV-2 epidemic. Targetin gut microbiota to regulate the process of SARS-CoV-2 infection should be a concern. Especially, the application of nanotechnology may provide help for further controlling COVID-19.

2.
Mol Cell Proteomics ; 2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-33148788

RESUMO

Malaria elimination is still pending on the development of novel tools that rely on a deep understanding of parasite biology. Proteins of all living cells undergo a myriad number of posttranslational modifications (PTMs) that are critical to multifarious life processes. An extensive proteome-wide dissection revealed a fine PTM map of most proteins in both Plasmodium falciparum, the causative agent of severe malaria, and the infected red blood cells. More than two-thirds of proteins of the parasite and its host cell underwent extensive and dynamic modification throughout the erythrocytic developmental stage. PTMs critically modulate the virulence factors involved in the host-parasite interaction and pathogenesis. Furthermore, P. falciparum stabilized the supporting proteins of erythrocyte origin by selective de-modification. Collectively, our multiple omic analyses, apart from having furthered a deep understanding of the systems biology of P. falciparum and malaria pathogenesis, provide a valuable resource for mining new antimalarial targets.

3.
Mol Oncol ; 2020 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-33155366

RESUMO

Deubiquitinase BAP1 is an important tumor suppressor in several malignancies, but its functions and critical substrates in prostate cancer (PCa) remain unclear. Here, we report that the mRNA and protein expression levels of BAP1 are downregulated in clinical PCa specimens. BAP1 can physically bind to and deubiquitinate PTEN, which inhibits the ubiquitination-mediated degradation of PTEN and thus stabilizes PTEN protein. Ectopically expressed BAP1 in PCa cells increases PTEN protein level and subsequently inhibits the AKT signaling pathway, thus suppressing PCa progression. Conversely, knockdown of BAP1 in PCa cells leads to the decrease of PTEN protein level and the activation of the Akt signaling pathway, therefore promoting malignant transformation and cancer metastasis. However, these can be reversed by the re-expression of PTEN. More importantly, we found that BAP1 protein level positively correlates with PTEN in a substantial fraction of human cancers. These findings demonstrate that BAP1 is an important deubiquitinase of PTEN for its stability and the BAP1-PTEN signaling axis plays a crucial role in tumor suppression.

4.
Signal Transduct Target Ther ; 5(1): 214, 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33033232

RESUMO

Epidermal growth factor receptor (EGFR) activation plays a pivotal role in EGFR-driven non-small cell lung cancer (NSCLC) and is considered as a key target of molecular targeted therapy. EGFR tyrosine kinase inhibitors (TKIs) have been canonically used in NSCLC treatment. However, prevalent innate and acquired resistances and EGFR kinase-independent pro-survival properties limit the clinical efficacy of EGFR TKIs. Therefore, the discovery of novel EGFR degraders is a promising approach towards improving therapeutic efficacy and overcoming drug resistance. Here, we identified a 23-hydroxybetulinic acid derivative, namely DPBA, as a novel EGFR small-molecule ligand. It exerted potent in vitro and in vivo anticancer activity in both EGFR wild type and mutant NSCLC by degrading EGFR. Mechanistic studies disclosed that DPBA binds to the EGFR extracellular domain at sites differing from those of EGF and EGFR. DPBA did not induce EGFR dimerization, phosphorylation, and ubiquitination, but it significantly promoted EGFR degradation and repressed downstream survival pathways. Further analyses showed that DPBA induced clathrin-independent EGFR endocytosis mediated by flotillin-dependent lipid rafts and unaffected by EGFR TKIs. Activation of the early and late endosome markers rab5 and rab7 but not the recycling endosome marker rab11 was involved in DPBA-induced EGFR lysosomal degradation. The present study offers a new EGFR ligand for EGFR pharmacological degradation and proposes it as a potential treatment for EGFR-positive NSCLC, particularly NSCLC with innate or acquired EGFR TKI resistance. DPBA can also serve as a chemical probe in the studies on EGFR trafficking and degradation.

5.
Chemosphere ; 264(Pt 2): 128495, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33038739

RESUMO

The vast usage of agrochemicals enhances food security globally but may pose challenge to understand the risk assessment to non-target organisms and human beings, and liver microsomes are responsible for metabolism of these agrochemicals in vivo. In this study, stereoselective metabolism of chiral triazole fungicide cyproconazole in rat liver microsomes has been investigated through chiral LC-MS/MS technique. The half-lives of four cyproconazole stereoisomers were different ranging from 95 to 187 min, and (2S, 3R)-cyproconazole preferentially metabolized in rat liver microsomes. In addition, the results from metabolism kinetic study indicated that rat liver microsomes showed the stronger potency to deplete (2S, 3R)-cyproconazole than the others. Then, homology modeling and molecular docking results revealed that the docking energy between (2S, 3R)-cyproconazole and the cytochrome P450 CYP3A1 (-7.46 kcal⋅mol-1) was higher than the others, meaning that (2S, 3R)-cyproconazole exhibited the strongest binding ability to this enzyme. Moreover, two main metabolites of cyproconazole coming from hydroxylation and dehydration were observed, and possible metabolic reactions of cyproconazole in rat liver microsomes were identified through using an LCQ ion trap mass spectrometer. This kind of systematic metabolic investigation of cyproconazole at chiral level would provide valuable information for ecological and human health risk assessment of chiral pesticides.

6.
Parasitology ; : 1-7, 2020 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-33087183

RESUMO

Toxoplasma gondii is an obligate intracellular protozoan parasite, which can infect almost all warm-blooded animals, including humans, leading to toxoplasmosis. Currently, the effective treatment for human toxoplasmosis is the combination of sulphadiazine and pyrimethamine. However, both drugs have serious side-effects and toxicity in the host. Therefore, there is an urgent need for the discovery of new anti-T. gondii drugs with high potency and less or no side-effects. Our findings suggest that lumefantrine exerts activity against T. gondii by inhibiting its proliferation in Vero cells in vitro without being toxic to Vero cells (P ≤ 0.01). Lumefantrine prolonged mice infected with T. gondii from death for 3 days at the concentration of 50 µg L-1 than negative control (phosphate-buffered saline treated only), and reduced the parasite burden in mouse tissues in vivo (P ≤ 0.01; P ≤ 0.05). In addition, a significant increase in interferon gamma (IFN-γ) production was observed in high-dose lumefantrine-treated mice (P ≤ 0.01), whereas interleukin 10 (IL-10) and IL-4 levels increased in low-dose lumefantrine-treated mice (P ≤ 0.01). The results demonstrated that lumefantrine may be a promising agent to treat toxoplasmosis, and more experiments on the protective mechanism of lumefantrine should be undertaken in further studies.

7.
Artigo em Inglês | MEDLINE | ID: mdl-33052668

RESUMO

Silicon (Si) has been considered as one of the most promising candidates for the next-generation lithium-ion battery (LIB) anode materials owing to its huge theoretical specific capacity of 4200 mA h g-1. However, the practical application of Si anodes in commercial LIBs is facing challenges because of the lack of scalable and cost-effective methods to prepare Si-based anode materials with proper microstructure and competitive electrochemical performances. Herein, we report a facile and scalable method to produce multidimensional porous silicon embedded with a nanosilver particle (pSi/Ag) composite from commercially available low-cost metallurgical-grade silicon (MG-Si) powder. The unique hybrid structure contributes to fast electronic transport and relieves volume change of silicon during the charge-discharge process. The pSi/Ag composite exhibits a large initial discharge capacity (3095 mA h g-1 at a high current of 1 A g-1), an excellent cycling performance (1930 mA h g-1 at 1 A g-1 after 50 cycles), and outstanding rate capacities (up to 1778 mA h g-1 at a higher current of 2 A g-1). After the samples are modified by reduced graphene oxide, the capacities of the pSi/Ag@RGO composite electrode can still be maintained over 1000 mA h g-1 after 200 cycles. This study provides a simple and effective strategy for production of high-performance anode materials.

8.
Artigo em Inglês | MEDLINE | ID: mdl-33091156

RESUMO

OBJECTIVE: This study aimed to compare the accuracy, efficiency, and consistency between experienced and less-experienced professionals using intelligent navigation echocardiography. METHODS: In this prospective study, we enrolled 93 fetuses with conotruncal defects (CTD) in the second and third trimesters from July 2017 to February 2018. One or more spatiotemporal image correlation (STIC) volume data sets were collected per case. The fetuses with CTD were diagnosed by the following two groups (n=20, each) of professionals with different experience levels using intelligent navigation echocardiography and two-dimensional ultrasound (2D US): group A with 15 years of experience and group B with 1 year of experience. The diagnostic consistency and accuracy of the technologies between the two groups were analyzed. RESULTS: Satisfactory consistency was noted in the two groups (group A, τ=0.855, P<0.05, and group B, τ=0.821, P<0.05), and no significant difference in accuracy (χ2=3.218, P>0.05) in using intelligent navigation echocardiography was reported between the two groups. However, there was a significant difference in accuracy (χ2=0.021, P<0.05) in using 2D US observed between the two groups. CONCLUSION: Intelligent navigation echocardiography was found to be efficient and accurate for the diagnosis of CTD and good consistency existed in the experienced and less-experienced professionals.

9.
Toxicol Appl Pharmacol ; 408: 115261, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33010263

RESUMO

Resveratrol, a type of natural polyphenol mainly extracted from the skin of grapes, has been reported to protect against inflammatory responses and exert anxiolytic effect. Yes-associated protein (YAP), a major downstream effector of the Hippo signaling pathway, plays a critical role in inflammation. The present study aimed to explore whether YAP pathway was involved in the anxiolytic effect of resveratrol in lipopolysaccharide (LPS)-treated C57BL/6J male mice. LPS treatment induced anxiety-like behavior and decreased sirtuin 1 while increased YAP expression in the hippocampus. Resveratrol attenuated LPS-induced anxiety-like behavior, which was blocked by EX-527 (a sirtuin 1 inhibitor). Mechanistically, the anxiolytic effects of resveratrol were accompanied by a marked decrease in YAP, interleukin-1ß and ionized calcium binding adaptor molecule 1 (Iba-1) while a significant increase in autophagic protein expression in the hippocampus. Pharmacological study using XMU-MP-1, a YAP activator, showed that activating YAP could induce anxiety-like behavior and neuro-inflammation as well as decrease hippocampal autophagy. Moreover, activation of YAP by XMU-MP-1 treatment attenuated the ameliorative effects of resveratrol on LPS-induced anxiety-like behavior, while blockade of YAP activation with verteporfin, a YAP inhibitor, attenuated LPS-induced anxiety-like behavior and neuro-inflammation as well as hippocampal autophagy. Finally, rapamycin-mediated promotion of autophagy attenuated LPS-induced anxiety-like behavior and decreased interleukin-1ß and Iba-1 expression in the hippocampus. Collectively, these results indicate that amelioration by resveratrol in LPS-induced anxiety-like behavior is through attenuating YAP-mediated neuro-inflammation and promoting hippocampal autophagy, and suggest that inhibition of YAP pathway could be a potential therapeutic target for anxiety-like behavior induced by neuro-inflammation.

10.
Chem Asian J ; 2020 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-32893986

RESUMO

Generally, bulk graphic carbon nitride (g-C3 N4 ) suffers from fast photogenerated charge carrier combination, inferior light absorption and insufficient active sites. Herein, we developed a defect engineering approach which can simultaneously realize O dopant and N defects in the g-C3 N4 framework via an acid-assisted thermal treatment route. The modified g-C3 N4 demonstrated greatly enhanced photocatalytic H2 activity with a H2 evolution rate of 2.20 mmol ⋅ g-1 ⋅ h-1 , which is more than three times higher than that of bulk g-C3 N4 . The mechanism of the enhanced activity was investigated and proposed that the introduction of O dopants and N defects in the g-C3 N4 could optimize the electron structure, up-shift the conduction band, increase the surface area, and thus achieve more efficient separation of photogenerated carriers, stronger reduction ability and abundant active sites for photocatalytic H2 evolution. Thus, defect engineering has been demonstrated to be a prospective strategy to modify the performance of g-C3 N4 for future photocatalytic energy generation.

12.
Molecules ; 25(15)2020 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-32731414

RESUMO

Rhus potaninii Maxim, a type of sumac, is an economically important tree widely cultivated in mountainous areas of western and central China. A gall, called the bellied gallnut, induced by the aphid, Kaburagia rhusicola Takagi, is important in the food, medical, and chemical industries in China. Volatiles from R. potaninii were found to attract K. rhusicola, but little is known about them. The chemical composition of these volatiles was investigated using GC-MS analysis and Y-tube olfactometer methods. Twenty-five compounds accounting for 55.3% of the volatiles were identified, with the highest proportion of 1-(4-ethylphenyl)ethanone (11.8%), followed by 1-(4-hydroxy-3-methylphenyl)ethanone (11.2%) and p-cymen-7-ol (7.1%). These findings provide a theoretical basis for the preparation of attractants and could eventually lead to increased bellied gallnut yield.

13.
Int Immunopharmacol ; 88: 106855, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32777676

RESUMO

Increased number of airway smooth muscle cells (ASMCs) is a characteristic of airway remodeling in asthma. In this study we investigated whether emodin alleviated airway remodeling in a murine asthma model and reduced the proliferation of ASMCs in vitro. We provided in vivo evidence suggesting that intraperitoneal injection of emodin (20 mg/kg) 1 h prior to OVA challenge apparently alleviated the thickness of airway smooth muscle, the mass of alpha-smooth muscle actin (α-SMA), collagen deposition, epithelial damage, goblet cell hyperplasia, airway inflammation and airway hyperresponsiveness (AHR) in lung tissue. Meanwhile, we found that emodin suppressed the activation of the Akt pathway in lungtissue of allergic mouse models. Additionally, we found that emodin inhibited cellular proliferation and Akt activation in a dose-dependent manner in vitro. Furthermore, LY294002, an inhibitor for PI3K, abrogated serum-induced phosphorylation of Akt, and decreased the proliferation of ASMCs. These findings indicated that emodin alleviated ASMCs proliferation by inhibiting PI3K/Akt pathway in vivo and in vitro, which may provide a potential therapeutic option for airway smooth muscle remodeling in asthma.

14.
World J Surg Oncol ; 18(1): 165, 2020 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-32669133

RESUMO

BACKGROUND: Inhibitory effect of endostar combined with radiotherapy on gastric cancer (GC) animal models and its effect on transforming growth factor-ß1 (TGF-ß1) and inter-leukin-10 (IL-10) were evaluated. METHODS: Forty mice of GC model xenograft tumors were prepared and randomly divided into blank control group, endostar group, radiotherapy group, and endostar combined with radiotherapy group (combination group). From the 14th day, a vernier caliper was used for measuring the long and short diameters of the xenograft tumors. The formula V = ab2/2 was used for calculating the tumor volume and to obtain its average value. Tumor growth curves were plotted to calculate the tumor inhibition rate. The growth of xenograft tumors and the behavioral changes of mice were observed. Enzyme-linked immunosorbent assay (ELISA) was used for detecting the expression levels of IL-10 and TGF-ß1. RESULTS: The tumor growth in the combination group was significantly inhibited, and the tumor volume was the smallest compared with the other groups (p < 0.05). Compared to the blank control group, the tumor inhibition rate was 11.8% in endostar group, 33.0% in radiotherapy group, and 52.1% in combination group (p < 0.01). Endostar combined with radiotherapy had an interaction in decreasing the expression levels of TGF-ß1 and IL-10 (F = 4.35 and 5.12, p < 0.05). Leucocyte count was significantly higher in control and combination groups than that in endostar and radiotherapy groups. The body weight of mice in endostar and radiotherapy groups decreased after treatment (p < 0.05). The body weight of mice after treatment in control and combination groups increased, with a statistically significant difference compared to that before treatment (p < 0.05). There was a statistically significant difference among all groups after treatment (F = 198.1, p < 0.01). CONCLUSIONS: Endostar combined with radiotherapy can inhibit tumor growth and downregulate the expression levels of TGF-ß1 and IL-10 through synergistic action.

15.
Eur Geriatr Med ; 2020 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-32691389

RESUMO

AIMS: To assess the efficacy and safety of iron supplementation for perioperative anemia in geriatric patients with hip fracture. METHODS: A systematic search was conducted for studies published using PubMed, EMBASE and Cochrane Library Databases that compared iron supplementation with placebo in patients undergoing hip fracture surgery. The outcomes were blood transfusion rate and volume, length of stay, infection and mortality (last follow-up). Sub-group and sensitivity analyses were performed in cases of substantial heterogeneity. RESULTS: The meta-analysis (6 studies: 1201 patients) indicated that iron supplements were not associated with reducing blood transfusion rate (OR 0.92, 95% CI 0.60-1.41; P = 0.69), but high heterogeneity (I2 = 61%) was detected and a significant association was found in sensitivity analysis of four studies (n = 637; OR 0.68, 95% CI 0.49-0.95; P = 0.02). A significant reduction was detected in transfusion volume (two studies: n = 234; MD - 0.45 units/patient, 95% CI - 0.74 to - 0.16; P = 0.002), hospital stay (five studies: n = 998; MD - 1.42, 95% CI - 2.18 to - 0.67; P = 0.0002) and caused no increased risk of mortality (five studies: n = 937; OR 0.94, 95% CI 0.65-1.36; P = 0.76) and infection (four studies: n = 701; OR 0.58, 95% CI 0.38-0.90; P = 0.01). Sub-group analyses of four studies showed that the preoperative intravenous use of iron at 200-300 mg (two studies) may be the beneficial option for hip fractures patients. CONCLUSIONS: Iron supplementation, especially preoperative intravenous use of 200-300 mg iron, is safe and associated with reducing transfusion requirement and hospital stay. Unfortunately, data were too limited to draw a definite conclusion. Further evaluation is required before recommending iron supplementation for older patients with hip fracture surgeries.

16.
Nanomedicine ; 29: 102261, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32621880

RESUMO

Oral administration shows good tolerance in patients. Botanic anticancer drugs without serious side effects have attracted increased attention worldwide. However, oral delivery of natural anticancer drugs faces great challenges due to low solubility, gastrointestinal side effects, first-pass effects, and P-glycoprotein efflux. Here, we loaded the natural polyphenol curcumin (Cc) into natural polysaccharide-cloaked lipidic nanocarriers (Cc@CLNs) to improve the efficacy in small-cell lung cancer (SCLC) associated with oral administration. Compared to other nanoformulations, Cc@CLNs have advantages of simple operation, easy scale-up, low cost, and high safety. Cc@CLNs improve bioavailability by inducing synergistic effects (efficient cell membrane penetration, inherent muco-adhesiveness, resistance to pepsin and trypsin degradation, promoted dissolution, enhanced epithelia/M cellular uptake and inhibition of efflux transporters) and countering the tendency of nanocarriers to aggregate and fuse, which limit lipid-based nanosystems. In this study, we first evaluated the oral bioavailability of Cc@CLNs in rats and their efficacy in H446 tumor-bearing mice. The oral bioavailability increased by 8.94-fold, and the tumor growth inhibition rate doubled compared to that achieved with free Cc. We investigated the action of Cc against SCLC stem cells, and Cc@CLNs greatly enhanced this action. The expression of CD133 and ABCG2 in the Cc@CLNs group decreased by 38.05% and 32.57%, respectively, compared to the respective expression levels in the control.

17.
Int J Cardiovasc Imaging ; 36(11): 2165-2172, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32642877

RESUMO

The main objective of this study was to investigate the diagnostic performance of FINE in generating and displaying 3 specific abnormal fetal echocardiography views such as left ventricular outflow tract (LVOT) view, right ventricular outflow tract (RVOT) view, and 3-vessels and trachea (3VT) view in fetuses with double-outlet right ventricle (DORV). In this prospective study, thirty fetuses diagnosed with DORV by fetal echocardiography in the second and third trimesters were enrolled. One or more STIC volume data-sets were collected from the 4-chamber view as initial view for each fetus, one optimal volume per fetus was selected for on-line analysis using FINE, and the diagnosis plane image was optimized using the Virtual Intelligent Sonographer Assistance (VIS-assistance).The visualization rates of 3 specific abnormal fetal echocardiography views of DORV and key diagnostic elements were calculated. One or more STIC volumes (n = 30 total) were obtained in 25 patients. A single STIC volume per patient was analyzed using the FINE method. FINE was able to successfully generate and display 3 specific abnormal fetal echocardiography views. The display rates of the 3 specific abnormal fetal echocardiography views (3VT, LVOT, RVOT) were 84.0%, 76.0% and 84.0%, respectively. By applying intelligent navigation technology to STIC volume data-sets, the FINE method can successfully generate three specific abnormal cardiac fetal echocardiography diagnostic views in fetuses with DORV, the FINE method can be used for screening and remote consultation of fetal DORV.


Assuntos
Inteligência Artificial , Diagnóstico por Computador , Dupla Via de Saída do Ventrículo Direito/diagnóstico por imagem , Ecocardiografia Quadridimensional , Coração Fetal/diagnóstico por imagem , Ultrassonografia Pré-Natal , Adulto , Pontos de Referência Anatômicos , Dupla Via de Saída do Ventrículo Direito/fisiopatologia , Feminino , Coração Fetal/anormalidades , Coração Fetal/fisiopatologia , Idade Gestacional , Humanos , Interpretação de Imagem Assistida por Computador , Valor Preditivo dos Testes , Gravidez , Reprodutibilidade dos Testes , Análise Espaço-Temporal , Adulto Jovem
18.
J Tradit Chin Med ; 40(3): 422-431, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32506856

RESUMO

OBJECTIVE: To investigate the effectiveness of osteoking, a Traditional Chinese Medicine originating from Yi nationality, against osteoporosis (OP) and osteoporotic fracture (OPF), and to elucidate its mechanism of action. METHODS: An osteoporotic fracture rat model was established; animals were divided into three treatment groups: parathyroid hormone, osteoking and 0.9%NaCl. After 4, 8 and 12 weeks of treatment, serum and bone tissues were collected. Enzyme-linked immuno sorbent assay, x-ray, histopathological evaluation and proteomics were used. Proteomics and GO annotation were performed based on identified peptides. The relative network was obtained from the STRING database and verified by polymerase chain reaction and Western blotting. RESULTS: After osteoking treatment, the bone mineral density (BMD) increased with time in the osteoking group. At week 12, the BMD and bone mineral salt content of the osteoking group were 4.5% and 20.6% higher than those of the negative control group, respectively. Furthermore, the body weight followed the order of positive control group > osteoking group > negative control group, with significant differences among the groups (P < 0.05). Micro-CT analysis of femur sections revealed that the bone surface/volume ratio was significantly higher in the osteoking group than that in the negative control group. X-ray images demonstrated that the osteoking group showed clear callus. Moreover, high-voltage micro-CT demonstrated a massive cortical bone accumulation in the osteoking group. The gray values of callus in the osteoking group were higher than those in the negative group. From week 4 to 12, the serum bone alkaline phosphatase level increased by 49.6% in the osteoking group and the serum propeptide of type Ⅰprocollagen level decreased by 80.6%. Alizarin red staining demonstrated that the calcium deposition in the osteoking group was higher than that in the negative control group. Notably, the expression of Mgp, a key osteogenesis inhibitor, was lower in the osteoking group compared with the negative control group. Moreover, Sparc, bone morphogenetic protein-2 and Bglap expression was higher in the osteoking group through activation of the transforming growth factor-receptor activator of nuclear factor κB Ligand pathway. CONCLUSION: Osteoking treatment increased bone quality and promoted calcium deposition. The results suggest that osteoking inhibits Mgp through the TGF-ß/RANKL pathway to improve OP/OPF.

19.
ACS Infect Dis ; 6(7): 1783-1795, 2020 07 10.
Artigo em Inglês | MEDLINE | ID: mdl-32485099

RESUMO

Toxin-antitoxin (TA) systems, which regulate many important cellular processes, are abundantly present in prokaryotic organisms. MazEF is a common type of TA system implicated in the formation of "persisters cells" of the pathogen Mycobacterium tuberculosis, which contains 10 such systems. However, the exact function and inhibition mode of each MazF protein are not quite understood. Here, we report four high-resolution crystal structures of MazF-mt1 in various forms, including one in complex with MazE-mt1. The toxin displayed two unique interlocked loops that allow the formation of a tight dimer. These loops would open upon interacting with the MazE-mt1 antitoxin mediated by the last two helices of MazE-mt1. With our structure-based design, a mutant that could bind to the antitoxin with an enhanced affinity was produced. Combined crystallographic and biochemical studies further revealed that the binding affinity of MazE-mt1 to MazF-mt1 was mainly attributed to its α3 helical region, while the terminal helix η1 contributes very little or even negatively to the association of the pair, in stark contrast to the MazEF-mt9 system. This study provides structural insight into the binding mode and the inhibition mechanism of the MazE/F-mt1 TA pair, which may reflect the functional differences between different TA systems.

20.
Nutr Cancer ; : 1-13, 2020 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-32590916

RESUMO

This study was to screen out potential driver long non-coding RNAs (lncRNAs) in lung cancer in Xuanwei (LCXW) differently expressed mRNAs and lncRNAs were detected by gene expression microarrays in 23 paired lung adenocarcinoma and adjacent tissues. Combined bioinformatics analysis was performed to identify potential driver lncRNAs and their potential regulatory relationships. Transcriptome and clinical data in TCGA-LUAD were used as comparison and validation dataset. The comparison of LCXW and TCGA-LUAD revealed significant differences in expression of some genes, signaling pathways affected by differentially expressed genes, and the 5-year survival rate of patients. We identified 14 consistently deregulated mRNAs and 5 lncRNAs as candidate genes, which affected multiple cancer-related pathways and influenced patients' overall survival. By combined bioinformatics analysis, we further identified a potential driver lncRNA fetal-lethal non-coding developmental regulatory RNA (FENDRR) and proposed its possible regulation mechanism. The low expression of FENDRR was positively correlated with Krüppel-like factor4 (KLF4), KLF4 down-regulation may loss the activation function of cyclin-dependent kinase inhibitor 1A (CDKN1A) and cyclin-dependent kinase inhibitor 1C (CDKN1C) and the inhibition function of CyclinB1 (CCNB1), eventually cause excessive cell cycle activation and lead to lung cancer. This study revealed a potential FENDRR-KLF4-cell cycle regulation axis. These results lay an important foundation for further research on the pathogenesis of LCXW and identification of potential novel biomarkers or therapeutic targets.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA