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1.
FASEB J ; 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31908049

RESUMO

Dense granule protein 12 (GRA12) is implicated in a range of processes related to the establishment of Toxoplasma gondii infection, such as the formation of the intravacuolar network (IVN) within the parasitophorous vacuole (PV). This protein is also thought to be important for T. gondii-host interaction, pathogenesis, and immune evasion, but their exact roles remain unknown. In this study, the contributions of GRA12 to the molecular pathogenesis of T. gondii infection were examined in vitro and in vivo. Deletion of GRA12 in type I RH and type II Pru T. gondii strains did not affect the parasite growth and replication in vitro, however, it caused a significant reduction in the parasite virulence and tissue cyst burden in vivo. T. gondii Δgra12 mutants were more vulnerable to be eliminated by host immunity, without the accumulation of immunity-related GTPase a6 (Irga6) onto the PV membrane. The ultrastructure of IVN in Δgra12 mutants appeared normal, suggesting that GRA12 is not required for biogenesis of the IVN. Combined deletion of GRA12 and ROP18 induced more severe attenuation of virulence compared to single Δgra12 or Δrop18 mutant strains. These data suggest a functional association between GRA12 and ROP18 that is revealed by the severe attenuation of virulence in a double mutant relative to the single individual mutations. Future studies are needed to define the molecular basis of this putative association. Collectively these findings indicate that although GRA12 is not essential for the parasite growth and replication in vitro, it contributes to the virulence and growth of T. gondii in mice.

2.
ACS Nano ; 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31895530

RESUMO

Viruses are associated with up to 15% of human cancer. MicroRNAs (miRNAs) encoded by numerous oncogenic viruses including Kaposi's sarcoma-associated herpesvirus (KSHV) play significant roles in regulating the proliferation and survival of virus-induced cancer cells, hence representing attractive therapeutic targets. Here, we report that specific inhibition of viral miRNAs by carbon dots (Cdots)-mediated delivery of locked nucleic acid (LNA)-based suppressors inhibit the proliferation of KSHV-associated primary effusion lymphoma (PEL) cells. Specifically, a combination of Cdots-LNAs to knock down the levels of KSHV miR-K12-1, miR-K12-4, and miR-K12-11 induces apoptosis and inhibits proliferation of PEL cells. Significantly, these Cdots-LNAs effectively inhibit the initiation of PEL and regress established PEL in a xenograft mouse model. These results demonstrate the feasibility of using Cdots to deliver miRNA suppressors for targeting viral cancers. Our study with viral miRNAs as targets may provide the scientific basis for using antisense drugs for human cancers associated with oncogenic viruses.

3.
J Clin Lab Anal ; : e23189, 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31916312

RESUMO

BACKGROUND: Osteosarcoma (OS) is one of the most common malignant bone tumors. It is essential to explore early diagnostic indicators with high sensitivity and specificity due to the rapid progression and metastasis of OS and the poor survival of metastatic OS patients. However, a few indicators of diagnostic significance have been described. METHODS: A total of 458 OS patients, 312 healthy individuals, and 228 patients with primary benign bone lesions were included. Logistic regression was performed on 46 clinical laboratory parameters to establish the diagnostic classifiers, which were evaluated by analysis of the receiver operating characteristic (ROC) curves. RESULTS: We established three diagnostic classifiers, called Cos for all ages, Clos for low ages, and Chos for high ages, with clinical laboratory parameters to distinguish OS from healthy individuals. All classifiers showed better diagnostic performances than alkaline phosphatase (ALP) in the independent validation cohort. In addition, these classifiers had better ability than ALP to discriminate OS from primary benign bone lesions. Furthermore, Cos , Clos, and Chos had larger AUC than ALP to identify small-size and early-stage OS and could also detect ALP-negative OS effectively. CONCLUSION: Our study suggests the potential of Cos , Clos , and Chos as non-invasive biomarkers for early OS.

4.
Brain Res ; : 146651, 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31926128

RESUMO

Reactive oxygen species, inflammation, and apoptosis are major contributors to secondary injuries that follow traumatic brain injury (TBI) in diabetic patients. Hydrogen (H2) can selectively neutralize reactive oxygen species and downregulate inflammatory and apoptotic factors. Therefore, we investigated the effects of inhaled high and low concentrations of hydrogen on neurological function after TBI in diabetic rats and the potential mechanism. We found that the inhalation of high concentrations of H2 significantly improved outcomes following TBI in diabetic rats. The inhalation of 42% H2 for one hour per day for 48 hours significantly reduced brain edema, decreased the extravasation of sodium fluorescein, and reduced oxidative stress markers (p<0.05). In addition, the inhalation of a high concentration of H2 (42% for one hour per day for 7 days) improved neurological deficits (p<0.05) and reduced the expression of apoptotic protein markers (p<0.05). However, the inhalation of 3% H2 did not yield significant effects. These results showed that the inhalation of 42% H2 can alleviate nerve damage and improve neurological function after TBI in diabetic rats. Therefore, the inhalation of a high concentration of H2 may be associated with the treatment of traumatic brain injuries.

5.
Artigo em Inglês | MEDLINE | ID: mdl-31925779

RESUMO

OBJECTIVE: To evaluate the effect of oral diosmin on the incidence and severity of ovarian hyperstimulation syndrome (OHSS) and explore the value of diosmin in preventing and treating OHSS. METHOD: A retrospective study of women attending a reproductive center in Guangzhou, China, between September and December 2016. The inclusion criterion was previous cancellation of embryo transfer after oocyte retrieval during IVF owing to a high risk of OHSS. The women were divided into two groups depending on whether they received oral diosmin (1000 mg twice daily for 10 days) after oocyte retrieval (diosmin group) or not (control group). Apart from diosmin, both groups underwent the same treatment. Baseline information and data related to OHSS were compared. RESULTS: Overall, 146 women were included: 74 in the diosmin group and 72 in the control group. The incidence of moderate-to-severe OHSS in the diosmin and control groups was 5/74 (6.2%) and 14/72 (13.4%), respectively (P=0.027). The control group included four cases of paracentesis due to ascites; there were no cases of paracentesis or severe OHSS in the diosmin group. CONCLUSION: Oral administration of diosmin effectively reduced both the incidence of moderate-to-severe OHSS and the severity of OHSS among high-risk women.

6.
Clin Rheumatol ; 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31897957

RESUMO

OBJECTIVE: Our study aimed to investigate the effect of illness uncertainty on sleep quality among SLE women. Meanwhile, the role of resilience was explored in the association of illness uncertainty with sleep quality. METHODS: This cross-sectional study was carried out from 2017 to 2018 in Liaoning province, China. Totally, 204 (81.6%) completed questionnaires concerning Pittsburgh Sleep Quality Index (PSQI), Mishel Uncertainty in Illness Scale for Adults (MUIS-A), Connor-Davidson Resilience Scale (CD-RISR), demographic, and clinical characteristics were collected. Multiple hierarchical regression analysis was used to test the associations of illness uncertainty, resilience, and the illness uncertainty*resilience interaction with sleep quality. The mediating role of resilience was explored by applying asymptotic and resampling strategies. RESULTS: The mean of PSQI score was 10.71 ± 3.68. Illness uncertainty was negatively related to sleep quality. The illness uncertainty*resilience interaction term was significantly associated with sleep quality. The effect of illness uncertainty on sleep quality was gradually weaken from low (1 SD below the mean, ß = 0.151, P < 0.001), mean (ß = 0.294, P < 0.001), to high (1 SD above the mean, ß = 0.437, P < 0.001) levels of resilience. Meanwhile, resilience partially mediated the association of illness uncertainty with sleep quality (a*b = 0.2383, BCa 95% CI: 0.1021, 0.3842). CONCLUSIONS: Poor sleep quality was the most frequent among SLE women. Illness uncertainty and resilience may be related factors associated with sleep quality. Thus, in practice, more targeted information support should be offered to increase illness perception. Moreover, more targeted psychological interventions based on resilience should be provided to enhance resilience in order to improve sleep qualityKey Points• Illness uncertainty may be related factor associated with sleep quality and negatively affected sleep quality among women with systemic lupus erythematosus (SLE).• Resilience acted as a moderator in the relationship between illness uncertainty and sleep quality among women with SLE. Meanwhile, resilience partially mediated the association of illness uncertainty with sleep quality.• More targeted information supports and psychological interventions based on resilience should be provided to enhance illness perception and resilience in order to improve sleep quality.

7.
Artigo em Inglês | MEDLINE | ID: mdl-31900986

RESUMO

BACKGROUND AND AIM: Recently, there has been burgeoning interest in the utilization of fully covered self-expandable metal stents (FCSEMSs) for managing main pancreatic duct strictures (MPDS) in chronic pancreatitis (CP). The primary aim was to investigate stricture resolution and recurrence rates of FCSEMS placement in patients with symptomatic CP complicated with MPDS. METHODS: MEDLINE, EMBASE, ISI Web of Science and Cochrane Library (up to December 2019) were searched to identify eligible studies. A meta-analysis of stricture resolution and recurrence rates was carried out using R. The crude rate of adverse events related to stent therapy was also calculated. RESULTS: Ten studies involving 163 patients were included. The weighted pooled rate of MPDS resolution was 93% [95% confidence interval (95%CI) 84%-99%] with substantial heterogeneity (I2 =63%). Duration of stent placement more than 3 months did not result in a significantly higher resolution rate than that of 3 months or less (93% vs 93%, P =0.91). The weighted pooled rate of stricture recurrence was 5% (95%CI: 0%-12%). The stricture recurrence rate for patients with duration of stent placement more than 3 months (3%; 95%CI: 0%-10%) was lower than that in patients with 3 months or less of stent placement (7%; 95%CI: 0%-23%), but not significantly (P = 0.45). The overall rate of adverse events related to stent therapy was 34.9% and spontaneous stent migration occurred in 14.1% of patients. CONCLUSIONS: The use of FCSEMSs appears to be effective and safe in the management of MPDS caused by symptomatic CP.

8.
Artif Cells Nanomed Biotechnol ; 48(1): 116-128, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31852257

RESUMO

In this study, we have designed a magnetic targeting pro-coagulant protein (MTPCP) for the embolic therapy of solid tumours. The MTPCP consists of a magnetic carrier and a pro-coagulant protein. The pro-coagulant protein used in this study is the fusion protein tTF-EG3287 which is not pro-coagulant when free in the blood circulation, but presents strong pro-coagulant ability once bound to the Neuropilin-1(NRP-1) that is highly expressed on tumour-associated vascular endothelial cells. And the magnetic carrier is O-Carboxymethyl chitosan-coated iron oxide nanoparticles (OCMC/Fe3O4). In vitro, we assessed the NRP-1 targeting ability of the MTPCP using confocal microscopy and flow cytometry, and evaluated the potential pro-coagulant activity of the MTPCP using the Spectozyme FXa assay. In vivo, the magnetic targeting ability of the MTPCP was detected using a living imaging system. At last, we assessed the anticancer activity of the MTPCP on HepG2 tumour bearing BALB/c nude mice models including subcutaneous transplantation and orthotopic transplantation. HepG2 tumour bearing mice models revealed that after intravenous administration of the MTPCP, thrombosis specifically occurs on tumour-associated blood vessels, and resulting in tumour growth retardation. No apparent side effects, such as thrombosis in other organs or other treatment-related toxicity, were observed during the treatment. Our data showed that the MTPCP may be a promising embolic agent for the embolic therapy of solid tumours.

9.
Mol Plant Pathol ; 21(1): 95-108, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31701600

RESUMO

Plants have evolved powerful immune systems to recognize pathogens and avoid invasions, but the genetic basis of plant susceptibility is less well-studied, especially to oomycetes, which cause disastrous diseases in many ornamental plants and food crops. In this research, we identified a negative regulator of plant immunity to the oomycete Phytophthora parasitica, AtRTP5 (Arabidopsis thaliana Resistant to Phytophthora 5), which encodes a WD40 repeat domain-containing protein. The AtRTP5 protein, which was tagged with green fluorescent protein (GFP), is localized in the nucleus and plasma membrane. Both the A. thaliana T-DNA insertion rtp5 mutants and the Nicotiana benthamiana RTP5 (NbRTP5) silencing plants showed enhanced resistance to P. parasitica, while overexpression of AtRTP5 rendered plants more susceptible. The transcriptomic analysis showed that mutation of AtRTP5 suppressed the biosynthesis of endogenous jasmonic acid (JA) and JA-dependent responses. In contrast, salicylic acid (SA) biosynthesis and SA-dependent responses were activated in the T-DNA insertion mutant rtp5-3. These results show that AtRTP5 acts as a conserved negative regulator of plant immunity to Phytophthora pathogens by interfering with JA and SA signalling pathways.

11.
World J Clin Cases ; 7(23): 3915-3933, 2019 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-31832394

RESUMO

Organic anion transporters (OATs) and organic anion transporter polypeptides (OATPs) are classified within two SLC superfamilies, namely, the SLC22A superfamily and the SLCO superfamily (formerly the SLC21A family), respectively. They are expressed in many tissues, such as the liver and kidney, and mediate the absorption and excretion of many endogenous and exogenous substances, including various drugs. Most are composed of 12 transmembrane polypeptide chains with the C-terminus and the N-terminus located in the cell cytoplasm. OATs and OATPs are abundantly expressed in the liver, where they mainly promote the uptake of various endogenous substrates such as bile acids and various exogenous drugs such as antifibrotic and anticancer drugs. However, differences in the locations of glycosylation sites, phosphorylation sites, and amino acids in the OAT and OATP structures lead to different substrates being transported to the liver, which ultimately results in their different roles in the liver. To date, few articles have addressed these aspects of OAT and OATP structures, and we study further the similarities and differences in their structures, tissue distribution, substrates, and roles in liver diseases.

12.
Org Lett ; 2019 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-31833772

RESUMO

An NHC-catalyzed cascade cycloaddition reaction is developed for quick access to structurally sophisticated tetrahydrochromeno[4,3-b]pyrrole derivatives. A sterically congested tetrasubstituted chirality carbon center is formed during the cyclization process. All the α-, ß-, and carbonyl carbons of the enal substrates are functionalized in chemo- and stereoselective fashion. The multicyclic chromeno[4,3-b]pyrrole products are generally afforded in good yields with excellent enantio- and diastereoselectivities. Heavily substituted pyrroline derivatives can be afforded from the chiral products through simple protocols.

13.
Artigo em Inglês | MEDLINE | ID: mdl-31837806

RESUMO

The C1q tumor necrosis factor (TNF)-related proteins 9 (CTRP9), an adipocyte-derived cytokine, affects a number of physiological processes, including immune function and inflammation. We investigated whether CTRP9 affects the expression of inflammation-related genes in Raw 264.7 and peritoneal macrophages. The CTRP9-induced expression of iNOS increased in a time- and dose-dependent manner. LPS and CTRP9 promote the expression of iNOS jointly in Raw 264.7 and peritoneal macrophages. CTRP9 induced the phosphorylation of JAK2 and STAT3 in Raw 264.7 and peritoneal macrophages. VX509 (JAK2 inhibitor) reduced the CTRP9-induced iNOS protein production. In addition, the CTRP9-induced phosphorylation of JAK2 and STAT3 was dramatically reduced by VX509. Collectively, these results suggest that JAK2/STAT3 signaling is involved in the CTRP9-induced expression of iNOS.

14.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(6): 1973-1978, 2019 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-31839069

RESUMO

OBJECTIVE: To explore the efficacy and safety of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of relapsed or refractory peripheral T-cell lymphoma(PTCL). METHODS: The clinical data of 6 patients with relapsed or refractory PTCL undergoing allo-HSCT from Sep. 2014 to Sep. 2018 in the department of hematology, aerospace center hospital were retrospectively analyzed. Complications and disease-free survival after HSCT were observed. RESULTS: All the patients could well tolerate the conditioning regimen and acquired hematopoietic recon-struction. Following up till December 2018, with a median time of 11.5 months (1-51); acute GVHD developed in 2 cases and chronic GVHD developed in 5 cases, Among 6 cases one case died of viral pheumonia and the other 5 patients remained disease-free survival. The longest disease-free survival time has reached 51 months. CONCLUSION: allo-HSCT is a safe and effective method for relapsed or refractory peripheral T-cell lymphoma, which can be chosen as salvage treatment method for patients with primary resistance. Optimization of the conditioning regimen may result in better efficacy of allo-HSCT.

15.
Food Funct ; 10(12): 7913-7925, 2019 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-31793594

RESUMO

Fritillaria is a perennial herb with bulbs with multiple medicinal usages. Here, we optimized extraction and hydrolysis methods for different species and origins of Fritillaria to study their anti-inflammatory activities. Using ultrasound-assisted hot water extraction after hydrolysis by hydrochloric acid and trifluoroacetate (TFA), monosaccharide derived from 1-phenyl-3-methyl-5-pyrazolone (PMP) was separated by using HPLC. The optimal conditions for hot water extraction were found via single factor analysis and orthogonal experiments. The PMP derivatization HPLC method could accurately determine the Mannose (Man), Glucose (Glu), Galactose (Gal), Xylose (Xyl), and Fucose (Fuc) content values in Fritillaria. This pre-column derivatization method is simple and rapid, providing less variation, high sensitivity and good reproducibility for saccharide separation. To study Fritillaria's anti-inflammatory effects in a mouse swelling model, HE-staining was performed to observe morphological changes in liver and kidney samples. Fritillaria's active ingredients could significantly inhibit mouse ear swelling induced by xylene and inhibit toe swelling induced by egg white. They mainly inhibited the secretion of inflammatory cytokines inside the body and maintained the dynamic balance between pro-inflammatory and anti-inflammatory factors in the body. According to histopathological analysis, Fritillaria had good anti-inflammatory activity against LPS-induced inflammation, reducing the expression of inflammatory cytokines.

16.
Artigo em Inglês | MEDLINE | ID: mdl-31818956

RESUMO

In adaptive immunity, organisms produce neutralizing antibodies (nAbs) to eliminate invading pathogens. Here, we explored whether viral neutralization could be attained through the physical disruption of a virus upon nAb binding. We report the neutralization mechanism of a potent nAb 8C11 against the hepatitis E virus (HEV), a nonenveloped positive-sense single-stranded RNA virus associated with abundant acute hepatitis. The 8C11 binding flanks the protrusion spike of the HEV viruslike particles (VLPs) and leads to tremendous physical collision between the antibody and the capsid, dissociating the VLPs into homodimer species within 2 h. Cryo-electron microscopy reconstruction of the dissociation intermediates at an earlier (15-min) stage revealed smeared protrusion spikes and a loss of icosahedral symmetry with the capsid core remaining unchanged. This structural disruption leads to the presence of only a few native HEV virions in the ultracentrifugation pellet and exposes the viral genome. Conceptually, we propose a strategy to raise collision-inducing nAbs against single spike moieties that feature in the context of the entire pathogen at positions where the neighboring space cannot afford to accommodate an antibody. This rationale may facilitate unique vaccine development and antimicrobial antibody design.

17.
Nano Lett ; 2019 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-31821006

RESUMO

Acquirement of aligned semiconducting single-walled carbon nanotube (s-SWNT) arrays is one of the most promising directions to break Moore's Law, thus developing the next-generation electronic devices. Despite that widespread approaches have been developed, it is still a great challenge to facilely prepare s-SWNT arrays with tunable electronic properties. Herein, a different perspective is proposed to produce s-SWNT arrays by implementing reversible methylation reactions on the as-grown aligned SWNT arrays. In this way, the metallic single-walled carbon nanotubes (m-SWNTs) are selectively and reversibly methylated to acquire semiconducting properties, to afford tunable electronic properties of the as-obtained SWNT arrays in a highly controllable and simple manner. Electrical measurements suggest a high fraction of s-SWNTs is attained (>97.5%) after methylation, facilitating its exceptional performance as a field-effect transistor (FET) with an on-off ratio of up to 17543. This method may provide a new way for the preparation of s-SWNT arrays with tunable electronic properties and impressive prospects toward the fabrication of high-performance FETs.

18.
Chem Commun (Camb) ; 2019 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-31825420

RESUMO

An efficient asymmetric [4+2] cycloaddition of 1-((2-aryl)vinyl)naphthalen-2-ols and in situ generated ortho-quinone methides with chiral phosphoric acid as the catalyst was developed. This reaction enables the highly enantioselective synthesis of chiral polysubstituted chromanes bearing multiple contiguous stereogenic centers in excellent yields and stereoselectivities (up to 99% yield, >95 : 5 dr and >99% ee).

19.
Biochim Biophys Acta Mol Basis Dis ; : 165625, 2019 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-31785406

RESUMO

One of the hallmarks of cancer progression is strong drug resistance during clinical treatments. The tumor microenvironment is closely associated with multidrug resistance, the optimization of tumor microenvironments may have a strong therapeutic effect. In this study, we configured polyacrylamide hydrogels of varying stiffness [low (10 kPa), intermediate (38 kPa) and high (57 kPa)] to simulate tissue physical matrix stiffness across different stages of breast cancer. After treatment with doxorubicin, cell survival rates on intermediate stiffness substrate are significantly higher. We find that high expression of ILK and YAP reduces the survival rates of breast cancer patients. Drug resistance is closely associated with the inactivation of the hippo pathway protein Merlin/MST/LATS and the activation of YAP. These results not only highlight the understanding of drug resistance mechanisms but also serve as a new basis for developing breast cancer treatment delivery systems.

20.
PLoS Negl Trop Dis ; 13(12): e0007913, 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31790412

RESUMO

BACKGROUND: The TGF-ß signalling pathway plays a key role in regulating dauer formation in the free-living nematode Caenorhabditis elegans, and previous work has shown that TGF-ß receptors are involved in parasitic nematodes. Here, we explored the structure and function of a TGF-ß type II receptor homologue in the TGF-ß signalling pathway in Haemonchus contortus, a highly pathogenic, haematophagous parasitic nematode. METHODOLOGY/PRINCIPAL FINDINGS: Amino acid sequence and phylogenetic analyses revealed that the protein, called Hc-TGFBR2 (encoded by the gene Hc-tgfbr2), is a member of TGF-ß II receptor family and contains conserved functional domains, both in the extracellular region containing cysteine residues that form a characteristic feature (CXCX4C) of TGF-ß II receptors, and in the intracellular regions containing a serine/threonine kinase domain. The Hc-tgfbr2 gene was transcribed in all key developmental stages of H. contortus, with particularly high levels in the infective, third-stage larvae (L3s) and male adults. Immunohistochemical results revealed that Hc-TGFBR2 was expressed in the intestine, ovary and eggs within the uterus of female adults, and also in the testes of male adults of H. contortus. Double-stranded RNA interference (RNAi) in this nematode by soaking induced a marked decrease in transcription of Hc-tgfbr2 and in development from the exsheathed L3 to the fourth-stage larva (L4) in vitro. CONCLUSIONS/SIGNIFICANCE: These results indicate that Hc-TGFBR2 plays an important role in governing developmental processes in H. contortus via the TGF-ß signalling pathway, particularly in the transition from the free-living to the parasitic stages.

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