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1.
Food Chem ; 306: 125616, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31622832

RESUMO

This research aimed to explore the role of protein S-nitrosylation in regulating the tenderness of postmortem beef, from the perspective of µ-calpain autolysis and protein proteolysis. Five bovine semimembranosus muscles were incubated with three treatments including S-nitrosoglutathione (GSNO, nitric oxide donor), normal saline and Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME, nitric oxide synthase inhibitor). The results showed that the level of protein S-nitrosylation was improved by GSNO treatment and reduced by L-NAME treatment (p < 0.05). Compared to the control, GSNO treatment had higher shear force while L-NAME treatment presented lower shear force at 7 d postmortem (p < 0.05). In addition, µ-calpain autolysis, myofibrillar protein and desmin degradation were reduced by GSNO treatment and accelerated by L-NAME treatment (p < 0.05). Therefore, it can be speculated that protein S-nitrosylation could affect beef tenderization by regulating the autolysis of µ-calpain and the degradation of myofibrillar proteins.

2.
Neurosci Lett ; 714: 134543, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31618668

RESUMO

BACKGROUND: Primary familial brain calcification (PFBC) is a rare neurodegenerative disorder characterized by calcium deposition in bilateral and symmetric brain. Evidence suggested that PFBC might be associated with paroxysmal kinesigenic dyskinesia (PKD). We aim to investigate the genetic causes in PFBC patients manifested as PKD, and further to explore the pathogenic impact of the identified mutations. METHODS: 4 PKD-mimic PFBC patients were investigated in the study. Clinical assessment including laboratory tests, head computed tomography (CT) were conducted and followed by exome sequencing. Variants of PFBC genes were screened, and Sanger sequencing, segregation analysis were applied to confirm the findings. Functional assessment of the identified mutations was further analyzed. RESULTS: Among the 4 PKD-mimic PFBC patients, 3 presented with brain calcification, and 1 was identified carrying a PFBC mutation but without brain calcification. The clinical characteristics were summarized. Three heterozygous variants (2 novel, 1 documented) in PFBC genes were found. Further functional study showed abnormal accumulation and reduced uptake of Pi of the mutant protein, and the aggregated PDGFB failing to induce membrane ruffles compared with wild-type. CONCLUSIONS: PKD can be a manifestation of PFBC, and brain calcification may be a cause of secondary PKD. So thoroughly evaluation including head CT or genetic screening for paroxysmal dyskinesia and PFBC should be applied before the diagnosis of PKD or PFBC. Moreover, negative brain calcification may not exclude the possibility of PFBC. The possible pathogenesis of primary calcification lie in the dysfunction of the protein or defective signal transduction caused by the mutations.

3.
Ecotoxicol Environ Saf ; 188: 109905, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31706245

RESUMO

Cooking oil fumes-derived PM2.5 (COFs-derived PM2.5) is the main source of indoor pollution. Exposure to COFs-derived PM2.5 can cause oxidative stress and affect angiogenesis. Here we investigated the roles of vitamin D3 (VD3) in protecting tubule formation injury induced by COFs-derived PM2.5, and the roles of ROS/NLRP3/VEGF signaling pathway in the effects. Human umbilical vein endothelial cells (HUVECs) were exposed to 0 (1‰ DMSO), 1000 nmol/l VD3, 100 µg/ml PM2.5, and 1000 nmol/l VD3 + 100 µg/ml PM2.5, respectively. Cell viability and tube formation, as well as protein and mRNA levels were measured. The results showed that exposure of COFs-derived PM2.5 dose-and time-dependently reduced the viability of HUVECs, increased the levels of mitochondrial and intracellular ROS, and changed the mitochondrial membrane potential level. While co-incubation with VD3 rescued these adverse effects. Both Western blot and real-time PCR (RT-PCR) showed that the expressions of NLRP3, caspase-1, Interleukin (IL)-1ß, and IL-18 in COFs-derived PM2.5 exposure group increased significantly, which could be effectively decreased by co-incubation with VD3. COFs-derived PM2.5 exposure could also reduce the expression of VEGF, while co-incubating HUVECs with VD3 evidently up-regulated the protein level of VEGF in HUVECs. In addition, COFs-derived PM2.5 could also inhibit the tube formation of HUVECs in vitro, which could be effectively rescued by the co-incubation of VD3. Our study proved that COFs-derived PM2.5 could damage the tubule formation of HUVECs in vitro, which could be effectively rescue by co-incubation with VD3, in which processes the ROS/NLRP3/VEGF signaling pathway played a crucial role. It provides a new theoretical basis for further study on the toxicity of PM2.5 to umbilical cord blood vessels.

4.
Ecotoxicol Environ Saf ; 188: 109756, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31711776

RESUMO

Soil co-contaminated with heavy metals and organics is often difficult to remediate. In this study, pot experiments were conducted to investigate the concurrent removal of cadmium (Cd, two levels: CdL [10 mg kg-1] and CdH [50 mg kg-1]) and trichlorfon (TCF, 100 mg kg-1) from co-contaminated soil by comparing the following remediation methods: natural remediation (NR), soil inoculated with Aspergillus sydowii (AS), soil planted with Brassica juncea (BJ), and soil planted with B. juncea and inoculated with A. sydowii (BJ-AS). The physiological responses of B. juncea and soil enzyme activities after remediation were also studied. B. juncea grew well in co-contaminated soil at both Cd levels. The biomass and chlorophyll content of B. juncea in CdH soil were lower than those in CdL soil, whereas the malondialdehyde content and activities of catalase, peroxidase and superoxide dismutase of B. juncea in CdH soil were higher than those in CdL soil. Cd accumulation in B. juncea was high in CdH soil, whereas high Cd removal efficiency was observed in CdL soil. TCF could be thoroughly degraded within 35 days in NR at both Cd-level soils. AS, BJ and BJ-AS promoted TCF degradation and enhanced the activities of catalase, urease, sucrase and alkaline phosphatase in soil compared with the NR. BJ-AS showed the highest phytoextraction ratio (3.32% in CdL and 1.34% in CdH soil) and TCF degradation rate (half-life of 2.18 and 2.37 days in CdL and CdH soil, respectively). These results demonstrate that BJ-AS could effectively remove Cd and TCF from soil and is thus a feasible technology for the bioremediation of these co-contaminated soil.

5.
Cancer Lett ; 468: 88-101, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31593800

RESUMO

Dysregulation of circular RNA Foxo3 (circFoxo3) has been reported to be involved in breast cancer and non-small lung cancer progression. However, little is known about the role of circFoxo3 in prostate cancer, which the present study seeks to investigate. CircFoxo3 expression was analyzed in 22 low-grade prostate cancer samples, 24 high-graded prostate cancer samples, and 18 normal prostate tissues, finding that its quantity was significantly decreased in high-graded compared to low-grade prostate cancer and normal prostate tissues. CircFoxo3 inhibited prostate cancer cell survival, migration, invasion and chemoresistance to docetaxel, which was related to circFoxo3's repression of Foxo3 and EMT. Silencing circFoxo3 expression promoted prostate cancer cell survival, migration, invasion and chemoresistance to docetaxel, as well as the positive effects of androgen on prostate cancer viability. Delivery of circfoxo3 enhanced chemosensitivity to docetaxel of prostate tumor-bearing mice and prolonged the life span of mice, while reduction with siRNAs promoted chemoresistance to docetaxel and shorted the life span of the tumor-bearing mice. Targeting circFoxo3/Foxo3/EMT may provide an applicable strategy for exploring potential prognostic and therapeutic approaches for prostate cancer.

6.
Pediatr Blood Cancer ; 67(1): e28027, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31571408

RESUMO

BACKGROUND: Radiotherapy boost to the entire posterior fossa (PF) is standard of care for high-risk (H-R) medulloblastoma patients; the utility of tumor bed (TB)-only boost is unclear. The purpose of this study was to examine the impact of PF versus TB boost volume on tumor control and survival in the H-R medulloblastoma population. METHODS: Single-institution records for patients with H-R medulloblastoma were reviewed. The median craniospinal irradiation dose was 36 Gy (range, 23.4-45 Gy), and boost doses to either PF or TB were 54 to 55.8 Gy. PF (local) failures were scored as in-field, marginal (between 80% and 95% isodose lines), or distant. Kaplan-Meier methods and Cox proportional hazards were used to assess the impact of radiation boost technique on local control (LC) and survival endpoints. RESULTS: Thirty-two patients with H-R medulloblastoma were treated between 1990 and 2015, with a median follow-up length of 5.12 years. Twenty-two patients received PF boost, and 10 received TB boost. Patient and disease characteristic were comparable between groups. A total of 11 PF failures occurred, including 3 isolated LFs (2 in the PF and 1 in the TB group). Most PF failures were in-field: three of four in the TB group and six of seven in the PF group; the remainder were marginal failures. TB boost was not associated with inferior LC (hazard ratio [HR] 0.86, log-rank P = 0.81) or overall survival (HR 1.40, P = 0.56) compared with PF boost. CONCLUSION: Reduced-volume radiotherapy boost to the TB does not appear to compromise LC or survival in patients with H-R medulloblastoma; it may reduce the risk of ototoxicity.

7.
Chemosphere ; 238: 124630, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31473530

RESUMO

Mercury (Hg) mining activities are an important anthropogenic source of atmospheric Hg. The Xunyang Hg mine located in Shaanxi Province is the largest active Hg producing centre in China. To understand the biogeochemical processes of atmospheric Hg through Hg mining activities, six groups of experimental pots were carefully designed to investigate the effect of Hg mining activities on Hg contamination from atmospheric deposition in the local surface soils. Based on the variations of Hg in the soil from the experimental pots, the deposition flux and loading of Hg in the Xunyang Hg mining district were investigated. The results showed that the average concentration of total gaseous mercury (TGM) as high as 193 ±â€¯122 ng m-3 was observed in the ambient air, which was orders of magnitude higher than that in remote areas. The average deposition flux and annual loading of atmospheric Hg were 72 mg m-2 y-1 and 10 t y-1, respectively. The dominant atmospheric Hg deposition is within a distance range of 6.0-12 km from the Hg retorting facility, accounting for approximately 85% of the total Hg loading. After 14 months of exposure, total mercury (THg) concentrations in the soil from the experimental pots increased 0.35-9.5 times, and the highest concentrations of methylmercury (MeHg) (3.7 ±â€¯2.9 µg kg-1) in soil were observed in February. Concentrations as high as 643 µg kg-1 THg and 13 µg kg-1 MeHg in rice were observed in the second experimental year. Elevated concentrations of both THg and MeHg in rice indicated that the newly deposited atmospheric Hg was bioavailable, readily methylated, and taken up by rice, suggesting that the ongoing Hg mining activities cause serious Hg contamination in the soil-rice ecosystem and posed a threat to local residents in the Xunyang Hg mining area.

8.
J Colloid Interface Sci ; 559: 21-28, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31605781

RESUMO

Biomass derived porous carbon was wildly used in non-precious metal carbon based electrocatalysts for ORR due to its low cost and sustainability. Here, we develop a facile route to prepare Co/N doped hemp derived highly porous carbon (Co/NHPC) as ORR electrocatalyst. The prepared Co/NHPC-90 possess 3D hierarchically porous nanostructure with high specific surface areas (1251 m2 g-1) and large pore volumes (0.99 cm3 g-1) due to the chemical activation of NaHCO3, which is benefit for the mass/electron transfer and exposure of active sites. In addition, melamine and cobalt nitrate were selected as nitrogen and metal source respectively to enrich the density of active sites. Thus, Co/NHPC-90 exhibits excellent ORR electrocatalytic performance with high half-wave potential (0.826 V), superior catalytic stability and tolerance to methanol.

9.
Nat Commun ; 10(1): 5525, 2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31797925

RESUMO

CRISPR-Cas9 is a widely-used genome editing tool, but its off-target effect and on-target complex mutations remain a concern, especially in view of future clinical applications. Non-human primates (NHPs) share close genetic and physiological similarities with humans, making them an ideal preclinical model for developing Cas9-based therapies. However, to our knowledge no comprehensive in vivo off-target and on-target assessment has been conducted in NHPs. Here, we perform whole genome trio sequencing of Cas9-treated rhesus monkeys. We only find a small number of de novo mutations that can be explained by expected spontaneous mutations, and no unexpected off-target mutations (OTMs) were detected. Furthermore, the long-read sequencing data does not detect large structural variants in the target region.

10.
Artigo em Inglês | MEDLINE | ID: mdl-31785250

RESUMO

PURPOSE: Postoperative pain is a negative factor that seriously affects a surgical patient's rehabilitation. We investigated whether nalbuphine provides superior postoperative analgesia in orthognathic surgery compared with sufentanil and whether the superior analgesia is achieved by the regulation of inflammatory and oxidative stress. PATIENTS AND METHODS: In the present randomized, double-blind, controlled clinical trial, 60 patients scheduled to undergo orthognathic surgery were randomized to receive 2.5 µg/kg of sufentanil (group S) or 2 mg/kg of nalbuphine (group N) for postoperative controlled intravenous analgesia. The primary outcome variable was the visual analog scale (VAS) score. The secondary outcome variables included the sedation score (Ramsay score) and plasma levels of inflammation factors, including tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), and oxidant stress factors, including malondialdehyde (MDA) and superoxide dismutase (SOD). RESULTS: The VAS scores of group N was significantly lower than those of group S, and the Ramsay scores for group N was greater. The plasma levels of TNF-α, IL-6, and MDA for group N were significantly lower than those for group S, and the SOD levels were greater than those for group S. Furthermore, the VAS scores correlated positively with the plasma levels of TNF-α, IL-6, and MDA and correlated negatively with the SOD levels. CONCLUSIONS: Nalbuphine offers better postoperative analgesia and sedation after orthognathic surgery. Nalbuphine also seems to provide superior postoperative analgesia by reducing inflammatory and oxidative stress.

11.
Mol Divers ; 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31792660

RESUMO

The present work describes the in vitro antibacterial evaluation of some new pyrimidine derivatives. Twenty-two target compounds were designed, synthesized and preliminarily explored for their antimicrobial activities. The antimicrobial assay revealed that some target compounds exhibited significantly inhibitory efficiencies toward bacteria and fungal including drug-resistant pathogens. Compound 7c presented the most potent inhibitory activities against Gram-positive bacteria (e.g., Staphylococcus aureus 4220), Gram-negative bacteria (e.g., Escherichia coli 1924) and the fungus Candida albicans 7535, with an MIC of 2.4 µmol/L. Compound 7c was also the most potent, with MICs of 2.4 or 4.8 µmol/L against four multidrug-resistant, Gram-positive bacterial strains. The toxicity evaluation of the compounds 7c, 10a, 19d and 26b was assessed in human normal liver cells (L02 cells). Molecular docking simulation and analysis suggested that compound 7c has a good interaction with the active cavities of dihydrofolate reductase (DHFR). In vitro enzyme study implied that compound 7c also displayed DHFR inhibition.

12.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 50(5): 689-694, 2019 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-31762239

RESUMO

OBJECTIVE: To assess changes in the cognitive function and hippocampal ultrastructure of elderly rats exposed to sevoflurane. METHODS: Ault male Sprague-Dawley rats were given subcutaneous injection of D-galactose on the neck for 40 d to establish elderly models, after 9-day behavioral training. The model rats were divided into 3 groups randomly: control group with natural air, A/O group with 6 h exposure to carrier gas (2 L/min Air+2 L/min O2), and Sev group with 6 h exposure to 3.2% sevoflurane through carrier gas. Morris Water Maze and balance beam experiment were conducted on 6 rats in each group 2 h, 1 week and 4 weeks after treatments, respectively. The hippocampal tissues of the rats were rapidly dissected and prepared by glutaraldehyde fixation, ethanol dehydration, infiltration, embedding polymerization, semimembrane section localization and staining for examinations under transmission electron microscopy. The hippocampal ultrastructure such as nucleus, cytoplasm, mitochondria, endoplasmic reticulum, medullary nerve fiber, synapse and apoptotic corpuscle were observed. RESULTS: Ethology: compared with the control and A/O groups, significant reductions in the probe trial capability were found in the rats after 2 h exposure to sevoflurane, which recovered at 1 week and 4 weeks. Sevoflurane also increased the working memory escape latency 2 h and 1 week after exposure. The balance beam experiment showed that sevoflurane prolonged the staring time of rats after 2 h exposure, which recovered at 1 week and 4 weeks. Prolonged length for going through the balance beam was found consistently in the rats exposed to sevoflurane. Transmission electron microscopy: rats in the control group were found to have clear hippocampal ultrastructure, intact nuclear membrane, no edema fluid in the cytoplasm, intact mitochondria and endoplasmic reticulum, normal medullary nerve fibers, intact synaptic structure, and no apoptotic bodies in the cells. But a small amount of edema were observed in the cytoplasm of hippocampal cells in the rats exposed to sevoflurane and A/O at 2 h, which increased at 1 week. The cytoplasmic morphology of rats in the A/O group returned to normal at 4 weeks. But further increase of edema was observed in the rats 4 weeks after exposure to sevoflurane. No abnormal morphological structures or apoptotic bodies in other organelles were found. CONCLUSIONS: Sevoflurane can induce early neurocognitive impairments in elderly rats, which may be related with changes in the hippocampus ultrastructure.


Assuntos
Envelhecimento , Cognição , Hipocampo/ultraestrutura , Sevoflurano/farmacologia , Animais , Hipocampo/efeitos dos fármacos , Masculino , Aprendizagem em Labirinto , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley
13.
Opt Express ; 27(20): 29045-29054, 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31684646

RESUMO

The wider deployment of commercial quantum key distribution (QKD) may benefit from an integrated system with reduced cost, small form-of-factor and high robutness. Silicon photonic circuits are good candidates while their performance stability in some contexts remains a challenge. We demonstrate a silicon photonic QKD transceiver based on time-bin protocol. The stability of the transceiver is investigated and a feedback function is proposed to improve the temperature-dependent performance of the transceiver. With the help of a faster data-processing ability, such scheme can facilitate more application scenarios, therefore achieving wider implementation of QKD in the future.

14.
Phys Rev Lett ; 123(18): 180504, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31763920

RESUMO

Quantum systems can be exploited for disruptive technologies but in practice quantum features are fragile due to noisy environments. Quantum coherence, a fundamental such feature, is a basis-dependent property that is known to exhibit a resilience to certain types of Markovian noise. Yet, it is still unclear whether this resilience can be relevant in practical tasks. Here, we experimentally investigate the resilient effect of quantum coherence in a photonic Greenberger-Horne-Zeilinger state under Markovian bit-flip noise, and explore its applications in a noisy metrology scenario. In particular, using up to six-qubit probes, we demonstrate that the standard quantum limit can be outperformed under a transversal noise strength of approximately equal magnitude to the signal, providing experimental evidence of metrological advantage even in the presence of uncorrelated Markovian noise. This work highlights the important role of passive control in noisy quantum hardware, which can act as a low-overhead complement to more traditional approaches such as quantum error correction, thus impacting on the deployment of quantum technologies in real-world settings.

15.
Biosci Rep ; 39(12)2019 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-31755521

RESUMO

RNA-seq analysis was used to identify differentially expressed genes (DEGs) at the genetic level in the longissimus dorsi muscle from two pigs to investigate the genetic mechanisms underlying the difference in meat quality between Debao pigs and Landrace pigs. Then, these DEGs underwent functional annotation, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, and protein-protein interaction (PPI) analyses. Finally, the expression levels of specific DEGs were assessed using qRT-PCR. The reference genome showed gene dosage detection of all samples which showed that the total reference genome comprised 22342 coding genes, including 14743 known and 190 unknown genes. For detection of the Debao pig genome, we obtained 14168 genes, including 13994 known and 174 unknown genes. For detection of the Landrace pig genome, we obtained 14404 genes, including 14223 known and 181 unknown genes. GO analysis and KEGG signaling pathway analysis show that DEGs are significantly related to metabolic regulation, amino acid metabolism, muscular tissue, muscle structure development etc. We identified key genes in these processes, such as FOS, EGR2, and IL6, by PPI network analysis. qRT-PCR confirmed the differential expression of six selected DEGs in both pig breeds. In conclusion, the present study revealed key genes and related signaling pathways that influence the difference in pork quality between these breeds and could provide a theoretical basis for improving pork quality in future genetic thremmatology.

16.
Artigo em Inglês | MEDLINE | ID: mdl-31698072

RESUMO

Two lipopolysaccharides (LPS) and ß-1, 3-glucan binding protein (LGBP), designated as PcLGBP isoform1 and PcLGBP isoform2, respectively, were identified from Procambarus clarkii in this study. The full-length cDNA of PcLGBP isoform1 was 1308 bp containing an open reading frame (ORF) of 1113 bp encoding a protein of 370 amino acids. The full-length cDNA of PcLGBP isoform2 was 1440 bp containing an ORF of 1245 bp encoding a protein of 414 amino acids. Predicted PcLGBP isoform1 and PcLGBP isoform 2 proteins contained a signal peptide, a glycoside hydrolase domain, and a low-complexity region. The difference between the two LGBP isoforms was that PcLGBP isoform2 had 44 more amino acids behind the signal peptide than the PcLGBP isoform1. The PcLGBP isoform1 and PcLGBP isoform2 transcripts mainly expressed in the hepatopancreas in female and male crayfish. Moreover, the expression levels of the two genes in the hepatopancreas were higher in male than that in female crayfish. Upon being challenged with Vibrio parahaemolyticus or LPS, the expression levels of PcLGBP isoform1 and PcLGBP isoform2 in the hepatopancreas of female and male crayfish were most significantly up-regulated at different time points. The transcripts of anti-lipopolysaccharide factors (ALF5, ALF6, ALF8, and ALF9) and crustins (CRU1, CRU2, CRU3, and CRU4) were evidently down-regulated in the hepatopancreas of V. parahaemolyticus-challenged total PcLGBP (including PcLGBP isoform1 and PcLGBP isoform2)-silenced male crayfish. In addition, the phenoloxidase (PO) activity in the hepatopancreas of male crayfish was evidently higher than that of female crayfish. PcLGBP knock down could significantly decrease the PO activity in the hepatopancreas lysate (HLS) in male crayfish. The PO activity of male crayfish HLS was significantly increased when incubated with a mixture of recombinant LGBP protein and LPS or ß-1, 3 glucan. We conclude that LGBP isoforms from P. clarkii function as a pattern recognition protein for recognizing and binding LPS and ß-1, 3 glucan, and thus regulate the synthesis of antimicrobial peptides and activate the prophenoloxidase system.

17.
Carcinogenesis ; 2019 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-31761927

RESUMO

Glioma is the most common brain tumor with high mortality. However, there are still challenges for the timely and accurate diagnosis and effective treatment of the tumor. 121 samples with grade II, III and IV from the Gene Expression Omnibus database were used to construct gene co-expression networks to identify hub modules closely related to glioma grade, and performed pathway enrichment analysis on genes from significant modules. In gene co-expression network constructed by 2345 differentially expressed genes from 121 gene expression profiles for glioma, we identified the black and blue modules that associated with grading. The module preservation analysis based on 118 samples indicates that the two modules were replicable. Enrichment analysis showed that the extracellular matrix genes were enriched for blue module, while cell division genes were enriched for black module. According to survival analysis, 21 hub genes were significantly up-regulated and one gene was significantly down-regulated. What's more, IKBIP, SEC24D and FAM46A are the genes with little attention among the 22 hub genes. In this study, IKBIP, SEC24D and FAM46A related to glioma were mentioned for the first time to the current knowledge, which might provide a new idea for us to study the disease in the future. IKBIP, SEC24D and FAM46A among the 22 hub genes identified that are related to the malignancy degree of glioma might be used as new biomarkers to improve the diagnosis, treatment and prognosis of glioma.

18.
J Steroid Biochem Mol Biol ; 196: 105507, 2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-31669572

RESUMO

Aromatase (CYP19A1) converts androgens into estrogens and is required for female sexual development and growth and development in both sexes. CYP19A1 is a member of cytochrome P450 family of heme-thiolate monooxygenases located in the endoplasmic reticulum and depends on reducing equivalents from the reduced nicotinamide adenine dinucleotide phosphate via the cytochrome P450 oxidoreductase coded by POR. Both the CYP19A1 and POR genes are highly polymorphic, and mutations in both these genes are linked to disorders of steroid biosynthesis. We have previously shown that R264C and R264H mutations in CYP19A1, as well as mutations in POR, reduce CYP19A1 activity. The R264C is a common polymorphic variant of CYP19A1, with high frequency in Asian and African populations. Polymorphic alleles of POR are found in all populations studied so far and, therefore, may influence activities of CYP19A1 allelic variants. So far, the effects of variations in POR on enzymatic activities of allelic variants of CYP19A1 or any other steroid metabolizing cytochrome P450 proteins have not been studied. Here we are reporting the effects of three POR variants on the aromatase activities of two CYP19A1 variants, R264C, and R264H. We used bacterially expressed and purified preparations of WT and variant forms of CYP19A1 and POR and constructed liposomes with embedded CYP19A1 and POR proteins and assayed the CYP19A1 activities using radiolabeled androstenedione as a substrate. With the WT-POR as a redox partner, the R264C-CYP19A1 showed only 15% of aromatase activity, but the R264H had 87% of aromatase activity compared to WT-CYP19A1. With P284L-POR as a redox partner, R264C-CYP19A1 lost all activity but retained 6.7% of activity when P284T-POR was used as a redox partner. The R264H-CYP19A1 showed low activities with both the POR-P284 L as well as the POR-P284 T. When the POR-Y607C was used as a redox partner, the R264C-CYP19A1 retained approximately 5% of CYP19A1 activity. Remarkably, The R264H-CYP19A1 had more than three-fold higher activity compared to WT-CYP19A1 when the POR-Y607C was used as the redox partner, pointing toward a beneficial effect. The slight increase in activity of R264C-CYP19A1 with the P284T-POR and the three-fold increase in activity of the R264H-CYP19A1 with the Y607C-POR point toward a conformational effect and role of protein-protein interaction governed by the R264C and R264H substitutions in the CYP19A1 as well as P284 L, P284 T and Y607C variants of POR. These studies demonstrate that the allelic variants of P450 when present with a variant form of POR may show different activities, and combined effects of variations in the P450 enzymes as well as in the POR should be considered when genetic data are available. Recent trends in the whole-exome and whole-genome sequencing as diagnostic tools will permit combined evaluation of variations in multiple genes that are interdependent and may guide treatment options by adjusting therapeutic interventions based on laboratory analysis.

19.
J Ethnopharmacol ; : 112204, 2019 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-31669442

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Ficus hispida L.f. (Moraceae) has long been used as a traditional medicine in India, China, Sri Lanka, Australia, and Myanmar in the treatment of diarrhea, ulcer, anemia, diabetes, inflammation, and cancer. AIM OF THE REVIEW: This review provides a systematic comment on the botany, traditional uses, and phytochemical and pharmacological studies of F. hispida, with an aim to make critical update of the current knowledge and obtain opportunities for further therapeutic potential. MATERIALS AND METHODS: The information was derived from scientific literature databases including PubMed, Baidu Scholar, Google Scholar, Web of Science, and Science Direct. Additional information was gathered from books, Ph.D. and M.Sc. dissertations, and unpublished materials. RESULTS AND DISCUSSION: F. hispida is used especially in Chinese and Indian traditional medical systems as a remedy for skin disorders, respiratory diseases, and urinary diseases. Wound healing, anti-inflammatory, antinociceptive, sedative, antidiarrheal, antiulcer, antimicrobial, antioxidant, hepatoprotective, antineoplastic, and antidiabetic activities have been reported for crude extracts and isolated metabolites, but the methodologies in these studies often have inadequate design and low technical quality. More than 76 compounds have been isolated from F.hispida, including sesquiterpenoids and triterpenoids, flavonoids, coumarins, phenylpropionic acids, benzoic acid derivatives, alkaloids, steroids, other glycosides, and alkanes, but the method of bioassay-guided fractionation is seldom applied in the isolation from F. hispida. CONCLUSION: F. hispida is used widely in traditional medicines and has multiple pharmacological effects that could support traditional uses. However, pharmacological studies should be viewed with caution because of the inappropriate experimental design. More in vitro and in vivo research is urgently needed to study the molecular mechanisms and assess the effective and safe dose of F. hispida.

20.
Front Immunol ; 10: 2465, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31681335

RESUMO

Background: Treg cells represent important viral reservoirs during chronic HIV infection. CD39 is closely involved in Treg-mediated immunosuppressive effects. However, CD39 expression on nTregs and mTregs and a relationship with HIV DNA levels during HIV infection is still unclear. In this study, we analyzed the distribution of HIV DNA in Treg subsets and the association between HIV DNA and CD39 expression on Treg subsets. Methods: Sixty-two HIV-infected patients with different HIV stages and 14 uninfected individuals were enrolled. nTregs (CD4+CD25+CD127lowCD45RO-) and mTregs (CD4+CD25+CD127lowCD45RO+) were isolated by magnetic selection and flow cytometric sorting. HIV DNA was quantified by real-time polymerase chain reaction (PCR). CD39 expression on nTregs and mTregs was analyzed by flow cytometry. Results: Higher levels of HIV DNA were detected in mTregs than those in nTregs during chronic HIV infection. The frequency of CD39+ nTregs and HIV DNA levels in nTregs were increased in patients with advanced HIV infection. Furthermore, HIV DNA levels in nTregs correlated positively with CD39+ nTreg frequency. CD39+ nTreg frequency was also increased in immune non-responders. Conclusions: mTregs and nTregs are both important reservoirs of virus during chronic HIV infection and HIV DNA levels increase in nTregs in patients with advanced HIV infection. We observed increased frequency of CD39+ nTregs and HIV DNA levels in nTregs in patients with advanced HIV infection. HIV DNA levels in nTregs correlated positively with CD39+ nTreg frequency.

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