Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.399
Filtrar
Mais filtros










Intervalo de ano de publicação
1.
Neurosurg Focus ; 47(6): E21, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31786555

RESUMO

OBJECTIVE: The aim of the present study was to investigate the practical value of a multimaterial and multicolor 3D-printed model in anatomical teaching, surgical training, and preoperative planning of transnasal endoscopic surgery for pituitary adenoma. METHODS: Multimodality neuroimaging data were obtained in a 42-year-old healthy male volunteer and a 40-year-old female patient with an invasive nonfunctional pituitary adenoma. Three 3D-printed models were produced: a monomaterial and monocolor model, a monomaterial and multicolor model, and a multimaterial and multicolor model. The effects on anatomical teaching and surgical training for exposing the vidian nerve were assessed by 12 residents, and the training effect was validated on cadavers. The practical values for preoperative planning were evaluated by 6 experienced neurosurgeons. All evaluations were based on 5-point Likert questionnaires. RESULTS: The multimaterial and multicolor model was superior to the monomaterial models in surgical training for exposing the vidian nerve (Fisher test; p < 0.05). In addition, the multimaterial and multicolor model was superior to the monomaterial models in anatomical teaching and preoperative planning (Friedman test; p < 0.05). CONCLUSIONS: Multimaterial and multicolor 3D printing technology makes it convenient and efficient to produce a practical model for simulating individualized and complex anatomical structures in the sellar region. Furthermore, the multimaterial model can provide a more realistic manipulative experience for surgical training and facilitate the preoperative planning.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31788933

RESUMO

Direct deprotonation represents an extremely simple, straightforward, and atom-economic strategy to activate the pronucleophiles bearing an acidic proton. However, the difficulty often arises while activating pronucleophiles with a low acidic proton by using conventional chiral tertiary amines. To overcome this great challenge, a handful of novel chiral Brønsted superbases, including amidines, guanidines, cyclopropenimines, and iminophosphoranes, have been discovered in recent years. This minireview mainly focuses on the application of these organosuperbases in the catalytic asymmetric reactions of low acidic pronucleophiles, and especially highlights their comparisons to the conventional tertiary amines, to demonstrate their highly efficient deprotonation processes and further stereoselectivity-controlled conversions. The advantage of these new superbases brings a great opportunity for developing more asymmetric transformations of low acidic pronucleophiles.

4.
Acta Pharmacol Sin ; 2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31796867

RESUMO

Increasing studies show that inflammatory processes may be involved in depressive disorders. Nuclear factor erythroid-2 related factor 2 (Nrf2) modulates tissue microglial M1 phenotypic changes to the M2 phenotype, which is implicated in protection against inflammatory diseases. We have reported that the adipose-derived mesenchymal stem cells (ADSCs) display anti-inflammatory activity. In this study we explored whether the mechanism of anti-inflammatory activity of ADSCs was related to Nrf2. ADSCs were isolated from mouse fat pads and intravenously administered to chronic mild stress (CMS)-exposed C57BL/6 mice at the dose of 1 × 106 once a week for 3 weeks. We showed that ADSC administration significantly remedied CMS-induced depressive-like behaviors in sucrose preference test, tail suspension test, and forced swim test accompanied by suppressing microglial activation and the expression of inflammatory factors including MCP-1, TNF-α, IL-1ß, and IL-6. Furthermore, ADSC administration promoted both the expression of BDNF and TrkB, and promoted Nrf2/HO-1 signaling but suppressed TLR4/NF-κB signaling in brain tissue. In order to elucidate the role of Nrf2/HO-1 signaling in ADSC-caused neuroprotection, Nrf2-modified ADSCs were cocultured with BV2 microglial cells, then exposed to lipopolysaccharide (LPS). Downregulation of Nrf2 in ADSCs decreased the protective effects of ADSCs against LPS-induced microglial activation and M1 polarization. Nrf2 overexpression in ADSCs markedly suppressed LPS-induced TLR4 and NF-κB expression in microglial cells. These results suggest a possible antidepressive mechanism correlated with microglial polarization for anti-inflammatory agents, which may provide a new microglia-targeted strategy for depression therapy.

5.
J Nat Prod ; 2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31804070

RESUMO

Twenty-six glucoconjugated monoterpene indole alkaloids, including 12 new compounds, rhynchophyllosides A-L (1-12), and 14 known ones, 13-26, were obtained from the hook-bearing stems of Uncaria rhynchophylla (Miq.) Miq. ex Havil. Their structures were unambiguously elucidated by analyses of UV, MS, NMR, ECD, and single-crystal X-ray diffraction data. The ESI-MSn behavior of the new glucoalkaloids was also elucidated. Although comprising the same glucosyl moiety, the aglycone skeletons and glucosidic numbers and linkage varied greatly, implying the diversity in biosynthetic pathways. This is the first report of such structurally diverse glucoconjugated monoterpene indole alkaloids from U. rhynchophylla. Compound 1 represents a new subtype of oxindole alkaloid with a seven-membered D-ring, 10 is a rare monoterpene indole alkaloid with the glucosyl moiety located at C-9, 4 and 5 are the first two oxindole alkaloid diglycosides, and 11 and 12 represent the first two examples of alkaloids with a quinolone nucleus from the genus Uncaria. Compound 10 exhibited moderate acetylcholinesterase (AChE) inhibitory activity with an IC50 value of 10.5 µM. Molecular docking was performed to explore the binding mode of inhibitor 10 at the active site of AChE.

6.
Nat Cell Biol ; 21(11): 1436-1448, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31685992

RESUMO

PTENα and PTENß are two longer translational variants of phosphatase and tensin homolog (PTEN) messenger RNA. Their expressional regulations and functions in carcinogenesis remain largely unknown. Here, we demonstrate that, in contrast with the well-established tumour-suppressive role of canonical PTEN, PTENα and PTENß promote tumourigenesis by directly interacting with the histone H3 lysine 4 (H3K4) presenter WDR5 to promote H3K4 trimethylation and maintain a tumour-promoting signature. We also show that USP9X and FBXW11 bind to the amino-terminal extensions of PTENα/ß, and respectively deubiquitinate and ubiquitinate lysines 235 and 239 in PTENα to regulate PTENα/ß stability. In accordance, USP9X promotes tumourigenesis and FBXW11 suppresses tumourigenesis through PTENα/ß. Taken together, our results indicate that the Pten gene is a double-edged sword for carcinogenesis, and reinterpretation of the importance of the Pten gene in carcinogenesis is warranted.

8.
Sci Rep ; 9(1): 15616, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31666604

RESUMO

MicroRNAs are known to play essential role in the gene expression regulation in cancer. In our research, next-generation sequencing technology was applied to explore the abnormal miRNA expression of oral squamous cell carcinoma (OSCC) in Chinese hamster. A total of 3 novel miRNAs (Novel-117, Novel-118, and Novel-135) and 11 known miRNAs (crg-miR-130b-3p, crg-miR-142-5p, crg-miR-21-3p, crg-miR-21-5p, crg-miR-542-3p, crg-miR-486-3p, crg-miR-499-5p, crg-miR-504, crg-miR-34c-5p, crg-miR-34b-5p and crg-miR-34c-3p) were identified. We conducted functional analysis, finding that 340 biological processes, 47 cell components, 46 molecular functions were associated with OSCC. Meanwhile the gene expression of Caspase-9, Caspase-3, Bax, and Bcl-2 were determined by qRT-PCR and the protein expression of PTEN and p-AKT by immunohistochemistry. Our research proposed further insights to the profiles of these miRNAs and provided a basis for investigating the regulatory mechanisms involved in oral cancer research.

9.
Exp Cell Res ; : 111714, 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31711919

RESUMO

FAM122A protein is a highly conserved in mammals, however its function is still largely unknown so far. In this study, we investigated the potential role of FAM122A in hepatocellular carcinoma (HCC). By analyzing HCC patient cohorts from RNA sequencing datasets, we found the expression level of FAM122A mRNA is significantly upregulated in HCC patients. Moreover, this abnormally higher expression pattern of FAM122A protein was also found in partial HCC tumor tissues, compared with the normal parts. Further, we demonstrated that CRISPR/Cas9-mediated FAM122A knockout significantly inhibits the growth, clonogenic potential and xenografts of HCC cells, induces cell cycle arrest and reduces the expression of proliferation-related genes. Interestingly, FAM122A deletion significantly enhances the cytotoxicity effect of Doxorubicin (Dox), a drug used in standard chemotherapy in HCC patients. In contrary, overexpression of FAM122A not only promotes HCC cell growth, but also inhibits Dox-induced DNA damage and cell death. Considering that FAM122A is previously identified as an endogenous inhibitor of PP2A, we asked whether FAM122A regulating HCC cell growth is associated with PP2A. The results showed FAM122A can also modulate PP2A activity in HCC cells although the modulated effect is relatively slight, however, treatment with a PP2A inhibitor okadaic acid did not rescue the inhibitory effects of cell growth and proliferation in FAM122A deletion cells, indicating that FAM122A may support HCC cell growth independent of its ability to modulate PP2A. Collectively, these results suggest that FAM122A is required for maintaining HCC cell growth, and its elimination combined with chemotherapy may represent a potential novel therapeutic strategy for HCC patients.

10.
J Ultrasound Med ; 2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31737929

RESUMO

OBJECTIVES: The aim of this study was to determine whether any salient differences exist in triple-negative breast cancer (TNBC) between premenopausal and postmenopausal patients by comprehensively comparing the ultrasound (US) and clinicopathologic features of these patients. METHODS: A detailed evaluation of the US and clinicopathologic features of 60 tumors from 60 patients with a diagnosis of TNBC (36 premenopausal and 24 postmenopausal women) was conducted in this retrospective study. RESULTS: Triple-negative breast cancer in premenopausal patients was more likely to show a round or oval shape and microlobulated margins, more commonly exerted effects on surrounding tissue, and showed grade 3 blood flow according to the method of Adler et al (Ultrasound Med Biol 1990; 16:553-559) compared with tumors in postmenopausal women. Triple-negative breast cancer in postmenopausal patients showed some similar US features as those observed in estrogen receptor-positive tumors, including irregular shapes, angular or spiculated margins, and nonparallel growth to the skin (P < .05 for all). CONCLUSIONS: Although US cannot be used to unequivocally identify TNBC, it can distinguish some salient US features regarding TNBC between premenopausal and postmenopausal women. Such information can then provide some valuable predictive information on the diagnosis of TNBC for clinicians.

11.
Carcinogenesis ; 2019 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-31740922

RESUMO

Colon signet-ring cell carcinoma (SRCC) is a rare type of malignant dedifferentiated adenocarcinomas, and is associated with poor survival. However, an in-depth study of the biological features of SRCC is hindered by the lack of a reliable in vitro model of colon SRCC. Thus, the establishment of cell cultures from SRCC has become the most challenging task. Here, by harnessing the power of the organoid culture system, we describe the establishment of a human colon SRCC organoid line from a surgical sample from one patient with colon SRCC. The colon SRCC organoid line, YQ-173, was characterized for morphology, histology, ultrastructure and chromosome stability levels, showing that it resembles the histological and growth characteristics of the original tumor cells; xenografts were used to show that it also has a high tumor formation rate. RNA sequencing of YQ-173 compared with the normal tissue verified its mucinous nature. Capture-based targeted DNA sequencing combined with drug screening based on a bespoke 88 compound library identified that JAK2 might be a treatment target. An in vitro drug screening found that AT9283 and Pacritinib could be effective JAK2 inhibitors, which was consistent with the in vivo xenograft response. We report, for the first time, the establishment of an SRCC organoid line allowing in-depth study of SRCC biology, as well as a strategy to assess in vitro drug testing in a personalized fashion.

12.
Molecules ; 24(21)2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31671644

RESUMO

Sesquiterpenoids constitute a marvelously varied group of natural products that feature a vast array of molecular architectures. Among them, the unusual bicyclo [6.3.0] undecane sesquiterpenoids are one of the most representative. To date, only approximately 42 naturally occurring compounds with this unique scaffold, which can be classified into seven different groups, have been reported. As the first-found member of each type, dactylol, asteriscanolide, dumortenol, toxicodenane C, and capillosanane S are characteristic of the four methyl groups on the five-eight-membered ring system. Only 11-hydroxyjasionone and sinuketal decorate the core with an isopropyl group. These natural products exhibit a wide range of bioactivities, including antifouling, anti-inflammatory, immune suppression, cytotoxic, antimutagenic, antiplasmodial, and antiviral activities. It was noted that some total syntheses of precapnellane-sesquiterpenoids (dactylol, poitediol, precapnelladiene), asteriscanolide, and 11-hydroxyjasionone have been achieved, because their cyclooctanoid core represents an important target for the development of synthetic strategies to prepare eight-membered ring-containing compounds. This review focuses on these natural sesquiterpenoids and their biological activities and synthesis, and aims to provide a foundation for further research of these interesting compounds.

13.
J Ethnopharmacol ; : 112336, 2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-31669102

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Aglaia odorata Lour. is a traditional Chinese medicinal plant possessing properties of improving blood circulation, and it is widely used in the treatment of dizziness, traumatic injuries and bruises. AIM OF STUDY: In this study, we are aimed to investigate the cerebral protection effect of the extracts from leaves of Aglaia odorata Lour. (ELA) and the potential mechanism in vivo and in vitro. MATERIALS AND METHODS: The therapeutic effect of ELA on ischemic cerebral stroke was measured on a middle cerebral artery occlusion (MCAO) rat model. Protective effect of ELA on oxygen-glucose deprivation/reperfusion (OGD/R)-induced PC12 cells was measured by MTT assay. The apoptotic cells were observed by Hoechst 33258 staining and acridine orange/ethidium bromide double staining assay. Mitochondria were observed by Mitotracker staining assay. The mitochondrial membrane potential was determined by JC-1 staining assay. Western blot was used to investigate the effects of ELA on apoptosis-related proteins. RESULTS: We showed that ELA was an effective neuroprotective agent. In vivo experiments, ELA exerted significant protective effect on MCAO model. TTC staining showed that ELA could reduce cerebral infarction area against MCAO insult. HE and Nissl's staining indicated that ELA could reverse the damage of cortex and hippocampus caused by MCAO. In vitro experiments, ELA showed significant protective effect on OGD/R-induced PC12 cells by reducing the number of apoptotic cells, increasing mitochondrial membrane potential, and reducing superoxide aggregation, further suppressing mitochondrial caspase-9/3 apoptosis pathway. Moreover, protective effect of ELA on mitochondrial function may be exerted by inhibiting p53/Puma signal pathway. CONCLUSION: Our results suggest that ELA exerts a marked neuroprotective effect against cerebral ischemia potentially via suppressing p53/Puma-mediated mitochondrial caspase-9/3 apoptosis pathway.

14.
Cancer Sci ; 2019 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-31710406

RESUMO

This study was designed to evaluate the dynamic survival and recurrence of remnant gastric cancer (RGC) after radical resection and to provide a reference for the development of personalized follow-up strategies. A total of 298 patients were analysed for their 3-year conditional overall survival (COS3), 3-year conditional disease-specific survival (CDSS3), corresponding recurrence and pattern changes, and associated risk factors. The 5-year OS and the 5-year DSS of the entire cohort were 41.2% and 45.8%, respectively. The COS3 and CDDS3 of RGC patients who survived for 5 years were 84.0% and 89.8%, respectively. The conditional survival in patients with unfavourable prognostic characteristics showed greater growth over time than in those with favourable prognostic characteristics (e.g., COS3, ≥T3: 46.4%-83.0%, Δ36.6% vs. ≤T2: 82.4%-85.7%, Δ3.3%; p<0.001). Most recurrences (93.5%) occurred in the first 3 years after surgery. The AJCC stage was the only factor that affected recurrence. Time-dependent Cox regression showed that for both OS and DSS, after 4 years of survival, the common prognostic factors that were initially judged lost their ability to predict survival (p >0.05). Time-dependent logistic regression analysis showed that the AJCC stage independently affected recurrence within two years after surgery (p < 0.05). A postoperative follow-up model was developed for RGC patients. In conclusion, patients with RGC usually have a high likelihood of death or recurrence within 3 years after radical surgery. we developed a postoperative follow-up model for RGC patients of different stages, which may affect the design of future clinical trials.

15.
Nat Commun ; 10(1): 5346, 2019 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-31767868

RESUMO

Human herpesvirus 6B (HHV-6B) belongs to the ß-herpesvirus subfamily of the Herpesviridae. To understand capsid assembly and capsid-tegument interactions, here we report atomic structures of HHV-6B capsid and capsid-associated tegument complex (CATC) obtained by cryoEM and sub-particle reconstruction. Compared to other ß-herpesviruses, HHV-6B exhibits high similarity in capsid structure but organizational differences in its CATC (pU11 tetramer). 180 "VΛ"-shaped CATCs are observed in HHV-6B, distinguishing from the 255 "Λ"-shaped dimeric CATCs observed in murine cytomegalovirus and the 310 "Δ"-shaped CATCs in human cytomegalovirus. This trend in CATC quantity correlates with the increasing genomes sizes of these ß-herpesviruses. Incompatible distances revealed by the atomic structures rationalize the lack of CATC's binding to triplexes Ta, Tc, and Tf in HHV-6B. Our results offer insights into HHV-6B capsid assembly and the roles of its tegument proteins, including not only the ß-herpesvirus-specific pU11 and pU14, but also those conserved across all subfamilies of Herpesviridae.

16.
Nucleic Acids Res ; 47(21): e137, 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31750522

RESUMO

Natural organisms have evolved intricate regulatory mechanisms that sense and respond to fluctuating environmental temperatures in a heat- or cold-inducible fashion. Unlike dominant heat-inducible switches, very few cold-inducible genetic switches are available in either natural or engineered systems. Moreover, the available cold-inducible switches still have many shortcomings, including high leaky gene expression, small dynamic range (<10-fold) or broad transition temperature (>10°C). To address these problems, a high-performance cold-inducible switch that can tightly control target gene expression is highly desired. Here, we introduce a tight and fast cold-inducible switch that couples two evolved thermosensitive variants, TFts and TEVts, as well as an additional Mycoplasma florum Lon protease (mf-Lon) to effectively turn-off target gene expression via transcriptional and proteolytic mechanisms. We validated the function of the switch in different culture media and various Escherichia coli strains and demonstrated its tightness by regulating two morphogenetic bacterial genes and expressing three heat-unstable recombinant proteins, respectively. Moreover, the additional protease module enabled the cold-inducible switch to actively remove the pre-existing proteins in slow-growing cells. This work establishes a high-performance cold-inducible system for tight and fast control of gene expression which has great potential for basic research, as well as industrial and biomedical applications.

18.
Chem Commun (Camb) ; 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31774076

RESUMO

The stability of zeolite Sn-beta (Sn-ß) was greatly improved for glucose isomerization to fructose and fructose yield of 41.5% has been obtained when dioxane/water was used as solvent. The effect of dioxane/water solvent mixtures for fructose dehydration on Amberlyst-131 was also studied and it was found that small amounts of water in dioxane increase the yield of HMF (up to 74%) by limiting the formation of oligomers like difructose anhydride (III). 56% yield of HMF from glucose, maltose, trehalose or cellobiose and 60% from sucrose were produced when hydrolysis of disaccharides, glucose isomerization and fructose dehydration were coupled in a mixture of dioxane/water (5 wt%).

19.
Chem Commun (Camb) ; 55(94): 14170-14173, 2019 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-31701971

RESUMO

A zinc-catalyzed decarboxylative A3 reaction of cyclic amino acids, α,ß-unsaturated aldehydes and terminal alkynes has been developed. A series of functionalized N-heterocyclic 1,6-enynes have been successfully obtained with excellent regioselectivities through this novel approach. In addition, the utility of this straightforward process is demonstrated by the preparation of a polycyclic nitrogen-containing heterocyclic compound.

20.
Parasit Vectors ; 12(1): 520, 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31690347

RESUMO

BACKGROUND: Cysticercosis caused by the metacestode larval stage of Taenia hydatigena is a disease of veterinary and economic importance. A considerable level of genetic variation among isolates of different intermediate hosts and locations has been documented. Generally, data on the genetic population structure of T. hydatigena is scanty and lacking in Nigeria. Meanwhile, similar findings in other cestodes like Echinococcus spp. have been found to be of epidemiological importance. Our aim, therefore, was to characterize and compare the genetic diversity of T. hydatigena population in Nigeria based on three mitochondrial DNA markers as well as to assess the phylogenetic relationship with populations from other geographical regions. METHODS: In the present study, we described the genetic variation and diversity of T. hydatigena isolates from Nigerian sheep and goats using three full-length mitochondrial genes: the cytochrome c oxidase subunit 1 (cox1), NADH dehydrogenase subunit 1 (nad1), and NADH dehydrogenase subunit 5 (nad5). RESULTS: The median-joining network of concatenated cox1-nad1-nad5 sequences indicated that T. hydatigena metacestodes of sheep origin were genetically distinct from those obtained in goats and this was supported by high FST values of nad1, cox1, and concatenated cox1-nad1-nad5 sequences. Genetic variation was also found to be higher in isolates from goats than from sheep. CONCLUSIONS: To the best of our knowledge, the present study described the genetic variation of T. hydatigena population for the first time in Nigeria using full-length mitochondrial genes and suggests the existence of host-specific variants. The population indices of the different DNA markers suggest that analysis of long mitochondrial DNA fragments may provide more information on the molecular ecology of T. hydatigena. We recommend that future studies employ long mitochondrial DNA sequence in order to provide reliable data that would explain the extent of genetic variation in different hosts/locations and the biological and epidemiological significance.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA