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1.
J Biol Chem ; : 101262, 2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34600889

RESUMO

Xylanases produce xylooligosaccharides (XOS) from xylan and have thus attracted increasing attention for their usefulness in industrial applications. Previously, we demonstrated that the GH11 xylanase XynLC9 from Bacillus subtilis formed xylobiose and xylotriose as major products with negligible production of xylose when digesting corncob-extracted xylan. Here, we aimed to improve the catalytic performance of XynLC9 via protein engineering. Based on sequence and structural comparisons of XynLC9 with the xylanases Xyn2 from Trichoderma reesei and Xyn11A from Thermobifida fusca, we identified the N-terminal residues 5-YWQN-8 in XynLC9 as engineering hotspots and subjected this sequence to site-saturation and iterative mutagenesis. The mutants W6F/Q7H and N8Y possessed a 2.6- and 1.8-fold higher catalytic activity than XynLC9, respectively, and both mutants were also more thermostable. Kinetic measurements suggested that W6F/Q7H and N8Y had lower substrate affinity, but a higher turnover rate (kcat), which resulted in increased catalytic efficiency compared to wild type XynLC9. Furthermore, the W6F/Q7H mutant displayed a 160% increase in the yield of XOS from corncob-extracted xylan. Molecular dynamics simulations revealed that the W6F/Q7H and N8Y mutations led to an enlarged volume and surface area of the active site cleft, which provided more space for substrate entry and product release, and thus accelerated the catalytic activity of the enzyme. The molecular evolution approach adopted in this study provides the design of a library of sequences that captures a meaning functional diversity in a limited number of protein variants.

2.
Mol Cancer Ther ; 2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34518296

RESUMO

A hallmark of pancreatic ductal adenocarcinoma (PDAC) is the presence of a dense, desmoplastic stroma and the consequent altered interactions between cancer cells and their surrounding tumor microenvironment (TME) that promote disease progression, metastasis, and chemoresistance. We have previously shown that IL6 secreted from pancreatic stellate cells (PSC) stimulates the activation of STAT3 signaling in tumor cells, an established mechanism of therapeutic resistance in PDAC. We have now identified the tumor cell-derived cytokine IL1α as an upstream mediator of IL6 release from PSCs that is involved in STAT3 activation within the TME. Herein, we show that IL1α is overexpressed in both murine and human PDAC tumors and engages with its cognate receptor IL1R1, which is strongly expressed on stromal cells. Further, we show that IL1R1 inhibition using anakinra (recombinant IL1 receptor antagonist) significantly reduces stromal-derived IL6, thereby suppressing IL6-dependent STAT3 activation in human PDAC cell lines. Anakinra treatment results in significant reduction in IL6 and activated STAT3 levels in pancreatic tumors from Ptf1aCre/+;LSL-KrasG12D/+; Tgfbr2flox/flox (PKT) mice. Additionally, the combination of anakinra with cytotoxic chemotherapy significantly extends overall survival compared with vehicle treatment or anakinra monotherapy in this aggressive genetic mouse model of PDAC. These data highlight the importance of IL1 in mediating tumor-stromal IL6/STAT3 cross-talk in the TME and provide a preclinical rationale for targeting IL1 signaling as a therapeutic strategy in PDAC.

3.
Clin Rheumatol ; 2021 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-34553293

RESUMO

BACKGROUND: Lupus erythematosus is an autoimmune disease that causes damage to multiple organs ranging from skin lesions to systemic manifestations. Cutaneous lupus erythematosus (CLE) is a common type of lupus erythematosus (LE), but its molecular mechanisms are currently unknown. The study aimed to explore changes in the gene expression profiles and identify key genes involved in CLE, hoping to uncover its molecular mechanism and identify new targets for CLE. METHOD: We analyzed the microarray dataset (GSE109248) derived from the Gene Expression Omnibus (GEO) database, which was a transcriptome profiling of CLE cutaneous lesions. The differentially expressed genes (DEGs) were identified, and the functional annotation of DEGs was performed with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Protein-protein interaction (PPI) network was also constructed to identify hub genes involved in CLE. RESULT: A total of 755 up-regulated DEGs and 405 down-regulated DEGs were identified. GO enrichment analysis showed that defense response to virus, immune response, and type I interferon signaling pathway were the most significant enrichment items in DEGs. The KEGG pathway analysis identified 51 significant enrichment pathways, which mainly included systemic lupus erythematosus, osteoclast differentiation, cytokine-cytokine receptor interaction, and primary immunodeficiency. Based on the PPI network, the study identified the top 10 hub genes involved in CLE, which were CXCL10, CCR7, FPR3, PPARGC1A, MMP9, IRF7, IL2RG, SOCS1, ISG15, and GSTM3. By comparison between subtypes, the results showed that ACLE had the least DEGs, while CCLE showed the most gene and functional changes. CONCLUSION: The identified hub genes and functional pathways found in this study may expand our understanding on the underlying pathogenesis of CLE and provide new insights into potential biomarkers or targets for the diagnosis and treatment of CLE. Key Points • The bioinformatics analysis based on CLE patients and healthy controls was performed and 1160 DEGs were identified • The 1160 DEGs were mainly enriched in biological processes related to immune responses, including innate immune response, type I interferon signaling pathway, interferon-γ-mediated signaling pathway, positive regulation of T cell proliferation, regulation of immune response, antigen processing, and presentation via MHC class Ib and so on • KEGG pathway enrichment analysis indicated that DEGs were mainly enriched in several immune-related diseases and virus infection, including systemic lupus erythematosus, primary immunodeficiency, herpes simplex infection, measles, influenza A, and so on • The hub genes such as CXCL10, IRF7, MMP9, CCR7, and SOCS1 may become new markers or targets for the diagnosis and treatment of CLE.

4.
Plant Sci ; 311: 111008, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34482911

RESUMO

The environmental damage caused by ozone is of increasing concern globally. The phosphoproteomics approach was used to explore the mechanisms underlying grapevine tolerance to ozone stress and identify phosphoproteins altered by ozone treatment. Results revealed that 194 of 2275 quantitatively analyzed phosphoproteins were significantly regulated after ozone treatment. Biological pathways related to transport were significantly enriched by the differentially regulated phosphoproteins. Among these phosphoproteins, the phosphorylation of RING E3 ligase in grape (V. vinifera KEEP ON GOING, VvKEG) decreased after ozone treatment. Over-expression of VvKEG in Arabidopsis decreased abscisic acid (ABA) sensitivity and enhanced ozone tolerance. Furthermore, VvKEG interacted with the ABA-responsive transcription factor ABSCISIC ACID-INSENSITIVE3 (ABI3). The exogenous application of ABA on grapevine leaves significantly influenced chlorophyll fluorescence, chlorophyll, and malondialdehyde (MDA) contents under ozone treatment; however, treatment with 150 µmol ABA aggravated ozone stress. These results indicate that phosphorylation modification provides information on ozone-induced processes and that VvKEG plays a critical role in these processes via regulation of the ABA signaling pathway in grape.


Assuntos
Adaptação Fisiológica/genética , Ozônio/efeitos adversos , Estresse Fisiológico/genética , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Vitis/genética , Vitis/fisiologia , Produtos Agrícolas/genética , Produtos Agrícolas/fisiologia , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Variação Genética , Genótipo , Fosforilação , Proteômica
5.
Lasers Surg Med ; 2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34487566

RESUMO

BACKGROUND: Various laser therapies have been introduced in scar management. However, pain during treatment has limited the application of laser therapy in pediatrics. OBJECTIVES: To evaluate whether the use of the low-energy mode of a carbon dioxide (CO2 ) laser improves hypertrophic scars in a pediatric population. METHODS: This prospective, randomized, split-scar trial was designed to assess the safety and efficacy of low-energy CO2 laser use. Patients aged <12 years with hypertrophic scars were enrolled. Each hypertrophic scar was equally divided into three parts: the two ends of each scar were randomly assigned to control and experimental groups, and the center portion was considered a transition zone and was not included in the analysis. A total of three laser treatments were performed at 1-month intervals. Scar scale scores 6 months after the final treatment was the primary outcome. Additionally, the Visual Analog Scale (VAS) was used to evaluate pain after each treatment. RESULTS: Of the 23 patients enrolled, 20 completed the study. The total Patient and Observer Scar Assessment Scale (POSAS) score at the 6-month follow-up was significantly lower for the treated site (44.95 for the treated group vs. 64.85 for the control group, p < 0.0001). Both the patient and observer POSAS scores showed an obvious difference between the treated and control groups (19.95 vs. 29.95 for patient scores, respectively, p < 0.0001, and 26.00 vs. 34.90 for observer scores, respectively, p < 0.0001). All observer and patient scores describing pain, pruritus, color, stiffness, and thickness were statistically different and favored the treated site. No significant difference was found in patient score of irregularity. The average VAS therapeutic pain score was 3.5 ± 1.43 out of 10. CONCLUSIONS: Low-energy CO2 fractional laser therapy improved hypertrophic scars in a pediatric population. Therefore, for children with hypertrophic scar, low-energy CO2 laser with less procedure pain may be more appropriate.

6.
Trials ; 22(1): 536, 2021 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-34391451

RESUMO

BACKGROUND: Acupuncture is effective for reducing the symptoms of neck pain (NP). However, the underlying mechanisms are not fully elucidated. Based on evaluating the efficacy of two acupuncture prescriptions for treating NP, this study aims to investigate the potential central mechanism of acupuncture treatment for NP by functional magnetic resonance imaging (fMRI). METHODS: This is a randomized controlled trial; 86 patients will be randomly assigned into two acupuncture treatment groups at a ratio of 1:1. The whole study period includes 2 weeks baseline, 2 weeks treatments, and 12 weeks follow-up (4 and 12 weeks after treatment). The pain severity, the neck disability index, the cervical range of motion, and the pressure pain threshold, etc., will be used to evaluate the clinical efficacy of two acupuncture prescriptions for NP treatment. The MRI scans will be performed to detect cerebral activity changes of 20 patients in each group. The clinical data and MRI data will be analyzed, respectively. Pearson correlation coefficient will be used to evaluate the association between changes of cerebral activity features and improvement of clinical symptoms. DISCUSSION: The results will provide further evidence for the clinical application of acupuncture in the treatment of NP. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2000040930 . Registered on 16 December 2020.


Assuntos
Terapia por Acupuntura , Cervicalgia , Terapia por Acupuntura/efeitos adversos , Humanos , Imageamento por Ressonância Magnética , Cervicalgia/diagnóstico por imagem , Cervicalgia/terapia , Manejo da Dor , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
8.
Environ Res ; 203: 111881, 2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34411547

RESUMO

In this study, waste cooking oil (WCO) co-fermentation with food waste by variable pH strategy was developed for microbial lipid production. Results showed that when WCO substitution rate within the range of 1.56-4.68% (corresponding to the WCO content in food waste), lipid production from Rhodosporidium toruloides 2.1389 could be increased by 7.2 g/kg food waste because of the better synergistic effect. Mechanism analysis revealed that the fatty acid salt produced from WCO under alkaline condition, as a surface active agent, could improve lipid production, but excessive WCO (29.2 g/L) would inhibit the lipid production due to its hindrance to the oxygen. The lipid composition analysis found that the produced lipid could be used as raw material for biodiesel production. It was estimated that 15.0 million tonnes of biodiesel could be produced from global food waste yearly by adopting the proposed WCO co-fermentation with variable pH strategy, together with reduction of about 0.31 million tonnes of CO2 equivalents and 1435 tonnes of SO2. It is expected that this study may lead to the paradigm shift in future biodiesel production from food waste.

9.
Glob Chang Biol ; 2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34416063

RESUMO

China has increased its vegetation coverage and enhanced its terrestrial carbon sink through ecological restoration since the end of the 20th century. However, the temporal variation in vegetation carbon sequestration remains unclear, and the relative effects of climate change and ecological restoration efforts are under debate. By integrating remote sensing and machine learning with a modelling approach, we explored the biological and physical pathways by which both climate change and human activities (e.g., ecological restoration, cropland expansion, and urbanization) have altered Chinese terrestrial ecosystem structures and functions, including vegetation cover, surface heat fluxes, water flux, and vegetation carbon sequestration (defined by gross and net primary production, GPP and NPP). Our study indicated that during 2001-2018, GPP in China increased significantly at a rate of 49.1-53.1 TgC/yr2 , and the climatic and anthropogenic contributions to GPP gains were comparable (48%-56% and 44%-52%, respectively). Spatially, afforestation was the dominant mechanism behind forest cover expansions in the farming-pastoral ecotone in northern China, on the Loess Plateau and in the southwest karst region, whereas climate change promoted vegetation cover in most parts of southeastern China. At the same time, the increasing trend in NPP (22.4-24.9 TgC/yr2 ) during 2001-2018 was highly attributed to human activities (71%-81%), particularly in southern, eastern, and northeastern China. Both GPP and NPP showed accelerated increases after 2010 because the anthropogenic NPP gains during 2001-2010 were generally offset by the climate-induced NPP losses in southern China. However, after 2010, the climatic influence reversed, thus highlighting the vegetation carbon sequestration that occurs with ecological restoration.

10.
Plant Cell ; 33(9): 2981-3003, 2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34240197

RESUMO

To overcome nitrogen deficiency, legume roots establish symbiotic interactions with nitrogen-fixing rhizobia that are fostered in specialized organs (nodules). Similar to other organs, nodule formation is determined by a local maximum of the phytohormone auxin at the primordium site. However, how auxin regulates nodule development remains poorly understood. Here, we found that in soybean, (Glycine max), dynamic auxin transport driven by PIN-FORMED (PIN) transporter GmPIN1 is involved in nodule primordium formation. GmPIN1 was specifically expressed in nodule primordium cells and GmPIN1 was polarly localized in these cells. Two nodulation regulators, (iso)flavonoids trigger expanded distribution of GmPIN1b to root cortical cells, and cytokinin rearranges GmPIN1b polarity. Gmpin1abc triple mutants generated with CRISPR-Cas9 showed the impaired establishment of auxin maxima in nodule meristems and aberrant divisions in the nodule primordium cells. Moreover, overexpression of GmPIN1 suppressed nodule primordium initiation. GmPIN9d, an ortholog of Arabidopsis thaliana PIN2, acts together with GmPIN1 later in nodule development to acropetally transport auxin in vascular bundles, fine-tuning the auxin supply for nodule enlargement. Our findings reveal how PIN-dependent auxin transport modulates different aspects of soybean nodule development and suggest that the establishment of auxin gradient is a prerequisite for the proper interaction between legumes and rhizobia.

11.
PLoS Comput Biol ; 17(7): e1009165, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34252084

RESUMO

miRNAs belong to small non-coding RNAs that are related to a number of complicated biological processes. Considerable studies have suggested that miRNAs are closely associated with many human diseases. In this study, we proposed a computational model based on Similarity Constrained Matrix Factorization for miRNA-Disease Association Prediction (SCMFMDA). In order to effectively combine different disease and miRNA similarity data, we applied similarity network fusion algorithm to obtain integrated disease similarity (composed of disease functional similarity, disease semantic similarity and disease Gaussian interaction profile kernel similarity) and integrated miRNA similarity (composed of miRNA functional similarity, miRNA sequence similarity and miRNA Gaussian interaction profile kernel similarity). In addition, the L2 regularization terms and similarity constraint terms were added to traditional Nonnegative Matrix Factorization algorithm to predict disease-related miRNAs. SCMFMDA achieved AUCs of 0.9675 and 0.9447 based on global Leave-one-out cross validation and five-fold cross validation, respectively. Furthermore, the case studies on two common human diseases were also implemented to demonstrate the prediction accuracy of SCMFMDA. The out of top 50 predicted miRNAs confirmed by experimental reports that indicated SCMFMDA was effective for prediction of relationship between miRNAs and diseases.

12.
Clin Interv Aging ; 16: 1265-1274, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34262266

RESUMO

Purpose: Elderly people represent a growing stroke population with different pathophysiological states than younger. Whether intravenous thrombolysis (IVT) before mechanical thrombectomy (MT) is beneficial for elderly patients remains unclear. This study compared the efficacy and safety between elderly patients treated with MT alone and those treated with both IVT and MT. Patients and Methods: Patients aged ≥65 years who were eligible for IVT within 4.5 h from symptom onset were selected from the ANGEL-ACT (Endovascular Treatment Key Technique and Emergency Work Flow Improvement of Acute Ischemic Stroke) registry, a prospective registry program for patients with endovascular treatment from 111 Chinese stroke centers. The primary efficacy outcome was the 90-day modified Rankin Scale score. We compared efficacy and safety outcomes using ordinal or binary logistic regression or a generalized linear model. Results: In total, 482 elderly patients were included: 187 (38.8%) received IVT and MT (bridging MT) and 295 (61.2%) received MT alone (direct MT). There was no significant difference in the 90-day modified Rankin Scale score between the two groups (median: 4 vs 4 points, respectively; adjusted ß=-0.048, P=0.822). The direct MT group had a shorter onset-to-puncture time (225 vs 255 min, respectively; adjusted ß=-55.074, P=0.002) and a lower rate of parenchymal hemorrhage type 2 within 24 h (2.80% vs 6.63%, respectively; adjusted odds ratio [OR]=0.287, 95% confidence interval [CI]=0.096-0.856, P=0.025). In addition, the direct MT group showed a trend toward a lower incidence of sICH (5.67% vs 10.06%, adjusted OR=0.453, P=0.061), procedure-related complications (7.12% vs 12.30%, adjusted OR=0.499, P=0.052) and distal or new territorial embolization (4.07% vs 6.95%, adjusted OR=0.450, P=0.093). Conclusion: Direct MT had similar efficacy to bridging MT in terms of the 90-day functional outcome in elderly patients, whereas bridging MT had a longer onset-to-puncture time and increased risk of hemorrhagic transformation and procedure-related complications.


Assuntos
Hemorragia Cerebral , Transtornos Cerebrovasculares , AVC Isquêmico , Trombectomia , Administração Intravenosa , Idoso , Hemorragia Cerebral/diagnóstico , Hemorragia Cerebral/etiologia , Transtornos Cerebrovasculares/complicações , Transtornos Cerebrovasculares/diagnóstico , Transtornos Cerebrovasculares/terapia , China/epidemiologia , Estudos de Coortes , Feminino , Humanos , AVC Isquêmico/tratamento farmacológico , AVC Isquêmico/etiologia , AVC Isquêmico/cirurgia , Masculino , Avaliação de Processos e Resultados em Cuidados de Saúde , Melhoria de Qualidade , Trombectomia/efeitos adversos , Trombectomia/métodos , Terapia Trombolítica/métodos , Fluxo de Trabalho
13.
Artigo em Inglês | MEDLINE | ID: mdl-34280110

RESUMO

This article is concerned with passivity analysis of neural networks with a time-varying delay. Several techniques in the domain are improved to establish the new passivity criterion with less conservatism. First, a Lyapunov-Krasovskii functional (LKF) is constructed with two general delay-product-type terms which contain any chosen degree of polynomials in time-varying delay. Second, a general convexity lemma without conservatism is developed to address the positive-definiteness of the LKF and the negative-definiteness of its time-derivative. Then, with these improved results, a hierarchical passivity criterion of less conservatism is obtained for neural networks with a time-varying delay, whose size and conservatism vary with the maximal degree of the time-varying delay polynomial in the LKF. It is shown that the conservatism of the passivity criterion does not always reduce as the degree of the time-varying delay polynomial increases. Finally, a numerical example is given to illustrate the proposed criterion and benchmark against the existing results.

14.
J Cancer Res Ther ; 17(3): 688-694, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34269300

RESUMO

Objective: The objective of the study was to compare the dose parameter and clinical efficacy of three-dimensional-printed template (3D-PT)-guided and traditional 125I seed implantation in treatment of gynecological tumors. Materials and Methods: A total of 28 patients with gynecological tumors treated with radioactive seed implantation in Hebei General Hospital from January 2016 to December 2018 were retrospectively analyzed. Twelve patients (template group) were guided by 3D-PT and the remaining 16 patients (traditional group) were guided by computed tomography (CT) with traditional technique. Preoperative treatment plan (preplan) was completed through a treatment planning system. In the template group, 3D-PT was printed according to preplan and seeds were implanted under the guidance of 3D-PT and CT. In the traditional group, seeds were implanted under the guidance of single CT directly according to the preplan. Postoperative verification plan (post-plan) was completed. Dose-volume histogram (DVH) was calculated and D80, D90, V90, V100, and V150 were obtained according to DVH. Then, deviation of the dosimetric parameters D80, D90, V90, V100, and V150 between the preplan and postplan were compared within the two groups. The difference and percentage of difference of the above dosimetric parameters between the preplan and postplan within the two groups were calculated using the formula Xd = Xpost-plan- Xpre-plan, and Xd% = (Xpost-plan- Xpre-plan)/Xpre-plan × 100%. Doses were calculated to determine whether the differences there were statistically significant. Efficacy evaluation was completed according to RECISIT 1.1. Local control rate and effective rate of 2-months postplan were compared between the two groups. Survival analysis was completed by the Kaplan-Meier method. The patients were followed up for 12 months, and their survival rate was calculated and compared. Results: There was no significant difference between the two groups for all the parameters, except for D80 of the preplan and postplan in the traditional group (P = 0.000). All the differences and percentage of difference were calculated and it was found that the Xd difference of D80 (P = 0.035), D90 (P = 0.023), V90 (P = 0.047), V100 (P = 0.032), and V150 (P = 0.031), as well as the Xd% difference of D80 (P = 0.032), D90 (P = 0.034), V90 (P = 0.042), V100 (P = 0.036), and V150 (P = 0.044) of the two groups was statistically significant, thus indicating that the dosimetric parameter fluctuation in the template group was more stable. The result of the curative effect after 2 months were as follows: the local control rate and effective rate of the template group were 100% (12/12) and 83.3% (10/12), while those of the traditional group were 100% (16/16) and 81.2% (13/16). There was no statistically significant difference in the curative effect between the two groups. After 6-27 months (median = 12 months) of follow-up, the median survival time of the template group and traditional group were 17 (10-23) and 16 (11-20) months, respectively, and the 1-year overall survival rate was 63% and 79% (P = 0.111), respectively, with no statistically significant difference observed. Conclusion: 3D-PT-guided 125I seed implantation is safe and effective in the treatment of gynecological tumors.

15.
J Vis Exp ; (171)2021 05 23.
Artigo em Inglês | MEDLINE | ID: mdl-34096926

RESUMO

Endoscopic middle ear surgery is a widely employed minimally invasive surgical technique to address middle ear and mastoid pathology. Bone drilling is the main technical challenge of endoscopic middle ear surgery. The accompanying video describes the detailed protocol of a constant-suction bone-drilling technique and the procedure of endaural exclusive endoscopic atticoantrotomy (retrograde mastoidectomy) using this technique. The main components of this bone-drilling technique include a soft and flexible suction tube, which is placed into the tympanic cavity to provide constant suction, and a soft sleeve, which is wrapped around the drill shaft to prevent the high-speed rotating shaft from damaging the lens of the endoscope. With these simple modifications, the traditional otological electrodrill can be used for drilling a tiny endaural incision in endoscopic middle ear surgery. Based on this bone-drilling technique, endaural endoscopic atticoantrotomy (retrograde mastoidectomy) can be successfully established for the removal of various amounts of bone, depending on the extent of the lesion. The short-term postoperative outcome seems promising.


Assuntos
Mastoidectomia , Orelha Média/cirurgia , Endoscopia , Humanos , Processo Mastoide/cirurgia , Sucção
16.
Nanotechnology ; 2021 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-34107464

RESUMO

Due to the diversity of sulfur valence in cobalt-based sulfides, it is difficult to control the crystal phase and composition of the products during synthesis. Herein, a one-pot hydrothermal method is reported to self-assemble the cobalt sulfides (CoS2, Co9S8 and Co3S4) with hollow nanostructures. The whole preparation process is simple and mild, avoiding high temperature calcination. The performances of the three kinds of cobalt sulfide in superior supercapacitors and electrocatalytic oxygen evolution performance applications follow the order of CoS2 > Co9S8 > Co3S4. Further analysis demonstrates that the performance difference in these cobalt sulfides may be attributed to three factors: the presence of S22-, the coordination environment of Co and the presence of continuous network of Co-Co bonds. The distinctive electrochemical performance of CoS2 and Co9S8 may help us to better understand the excellent electrochemical activity of metal polysulfides and metal sulfides after doping or alloying. Therefore, this work may provide a reference in understanding and designing the electrode materials for highly efficient applications in the fields of energy storage and conversion.

17.
Bioorg Chem ; 114: 105072, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34144276

RESUMO

Random screening revealed that the EtOH extract of Artemisia atrovirens showed significant cytotoxicity against two human hepatoma cell lines (HepG2 and Huh7) with the inhibitory ratio of 98.9% and 99.7% at the concentration of 100 µg/mL. Further bioactivity-guided isolation of active fraction led to 16 new guaiane-type sesquiterpenoids, artematrovirenins A-P (1-16). Their structures were elucidated by extensive spectroscopic data. The absolute stereochemistry of compounds 1 and 14 was determined by single-crystal X-ray diffraction analyses. Pharmacological evaluation suggested that five compounds (3, 5, 8, 10, and 15) exhibited cytotoxicity, compounds 3 and 5 displayed cytotoxicity against HepG2 cell line with an IC50 values of 8.0 and 16.0 µM, as well as against Huh7 cell line with values of 18.2 and 32.2 µM.

18.
J Mol Neurosci ; 71(10): 2035-2052, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33970426

RESUMO

White matter damage is a component of most human stroke and usually accounts for at least half of the lesion volume. Subcortical white matter stroke (WMS) accounts for 25% of all strokes and causes severe motor and cognitive dysfunction. The adult brain has a very limited ability to repair white matter damage. Pathological analysis shows that demyelination or myelin loss is the main feature of white matter injury and plays an important role in long-term sensorimotor and cognitive dysfunction. This suggests that demyelination is a major therapeutic target for ischemic stroke injury. An acute inflammatory reaction is triggered by brain ischemia, which is accompanied by cytokine production. The production of cytokines is an important factor affecting demyelination and myelin regeneration. Different cytokines have different effects on myelin damage and myelin regeneration. Exploring the role of cytokines in demyelination and remyelination after stroke and the underlying molecular mechanisms of demyelination and myelin regeneration after ischemic injury is very important for the development of rehabilitation treatment strategies. This review focuses on recent findings on the effects of cytokines on myelin damage and remyelination as well as the progress of research on the role of cytokines in ischemic stroke prognosis to provide a new treatment approach for amelioration of white matter damage after stroke.

19.
Cancer Res ; 81(15): 4001-4013, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-33990397

RESUMO

In pancreatic cancer, the robust fibroinflammatory stroma contributes to immune suppression and renders tumors hypoxic, altering intratumoral metabolic pathways and leading to poor survival. One metabolic enzyme activated during hypoxia is lactate dehydrogenase A (LDHA). As a result of its promiscuous activity under hypoxia, LDHA produces L-2 hydroxyglutarate (L-2HG), an epigenetic modifier, that regulates the tumor transcriptome. However, the role of L-2HG in remodeling the pancreatic tumor microenvironment is not known. Here we used mass spectrometry to detect L-2HG in serum samples from patients with pancreatic cancer, comprising tumor cells as well as stromal cells. Both hypoxic pancreatic tumors as well as serum from patients with pancreatic cancer accumulated L-2HG as a result of promiscuous activity of LDHA. This abnormally accumulated L-2HG led to H3 hypermethylation and altered gene expression, which regulated a critical balance between stemness and differentiation in pancreatic tumors. Secreted L-2HG inhibited T-cell proliferation and migration, suppressing antitumor immunity. In a syngeneic orthotopic model of pancreatic cancer, inhibition of LDH with GSK2837808A decreased L-2HG, induced tumor regression, and sensitized tumors to anti-PD1 therapy. In conclusion, hypoxia-mediated promiscuous activity of LDH produces L-2HG in pancreatic tumor cells, regulating the stemness-differentiation balance and contributing to immune evasion. Targeting LDH can be developed as a potential therapy to sensitize pancreatic tumors to checkpoint inhibitor therapy. SIGNIFICANCE: This study shows that promiscuous LDH activity produces L-2HG in pancreatic tumor and stromal cells, modulating tumor stemness and immune cell function and infiltration in the tumor microenvironment.

20.
Behav Brain Res ; 410: 113357, 2021 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-33989729

RESUMO

Post-stroke cognitive impairment (PSCI) is one of the most common complications of stroke, it is also an important reason for the poor prognosis in stroke patients with motor and speech dysfunction. Enriched Environment (EE), a novel and easy-to-implement rehabilitation treatment strategy, is thought to be a potential intervention for PSCI recently. In this paper, we review the therapeutic effects and related mechanisms of EE in PSCI from the level of animal research and clinical application. Besides, we further discuss the application prospects and limitations of EE in PSCI patients.

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