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1.
ISME J ; 2020 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-32132664

RESUMO

Studies of marine benthic archaeal communities are updating our view of their taxonomic composition and metabolic versatility. However, large knowledge gaps remain with regard to community assembly processes and inter taxa associations. Here, using 16S rRNA gene amplicon sequencing and qPCR, we investigated the spatiotemporal dynamics, assembly processes, and co-occurrence relationships of the archaeal community in 58 surface sediment samples collected in both summer and winter from across ~1500 km of the eastern Chinese marginal seas. Clear patterns in spatiotemporal dynamics in the archaeal community structure were observed, with a more pronounced spatial rather than seasonal variation. Accompanying the geographic variation was a significant distance-decay pattern with varying contributions from different archaeal clades, determined by their relative abundance. In both seasons, dispersal limitation was the most important process, explaining ~40% of the community variation, followed by homogeneous selection and ecological drift, that made an approximately equal contribution (~30%). This meant that stochasticity rather than determinism had a greater impact on the archaeal community assembly. Furthermore, we observed seasonality in archaeal co-occurrence patterns: closer inter-taxa connections in winter than in summer, and unmatched geographic patterns between community composition and co-occurrence relationship. These results demonstrate that the benthic archaeal community was assembled under a seasonal-consistent mechanism but the co-occurrence relationships changed over the seasons, indicating complex archaeal dynamic patterns in coastal sediments of the eastern Chinese marginal seas.

4.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 34(2): 179-183, 2020 Feb 15.
Artigo em Chinês | MEDLINE | ID: mdl-32030948

RESUMO

Objective: To evaluate the effectiveness of total scapular arthroplasty after total scapulectomy for scapular tumors. Methods: A clinical data of 17 patients with scapular tumors treated with total scapulectomy and total scapular arthroplasty between January 2010 and December 2017 were retrospectively reviewed. There were 9 males and 8 females with an average age of 34.4 years (range, 13-64 years). Seven patients were diagnosed with chondrosarcoma, 3 with osteosarcoma, 2 with Ewing's sarcoma, 1 with high-grade sarcoma, 1 with polymorphic dedifferentiated sarcoma, 1 with fibrosarcoma, 1 with plasmacytoma, and 1 with bone giant cell tumor. According to the surgical staging system described by Enneking et al, 1 patient was rated as stage 3, 8 as stageⅠB, 8 as stageⅡB. According to the classifications of shoulder girdle resections of Malawer et al, 11 patients were type ⅢB, 5 were type ⅣB, 1 was type ⅥB. The disease duration ranged from 0.5 to 8.0 months (mean, 3.2 months) and tumor size ranged from 11.0 cm×7.5 cm×6.0 cm to 18.5 cm×18.0 cm×12.5 cm. The 1993 Musculoskeletal Tumor Society (MSTS) upper limb function scoring system and shoulder mobility were used to evaluate postoperative shoulder joint function. Tumor recurrence and metastases were monitored by radiograph. Results: Poor superficial incision healing occurred in 1 patient, the rest incisions achieved healing by first intention. All patients were followed up 20-72 months (mean, 45.4 months). Two of the 17 patients died of multiple organ dysfunction syndrome caused by tumor metastases; 3 patients suffered from pulmonary metastases and were alive with disease. No local recurrence occurred in all patients. The overall survival rate was 88.2% (15/17) and the disease-free survival rate was 70.6% (12/17). Rib fracture after trauma, aseptic loosening, and atrophy of the deltoid muscle occurred in 1, 1, and 1 case, respectively. The other related complication was not observed. At last follow-up, the MSTS score was 26.1±1.4, and the flexion, extension, and abduction range of motion of shoulder joint were (70.0±7.5), (31.2±11.3), and (54.4 ±12.5) °, respectively. Conclusion: Reconstruction with total scapular arthroplasty after total scapulectomy can obtain a satisfactory shoulder contour and an acceptable functional outcomes in patients with scapular tumors.


Assuntos
Artroplastia , Neoplasias Ósseas , Articulação do Ombro , Adolescente , Adulto , Neoplasias Ósseas/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estudos Retrospectivos , Escápula , Resultado do Tratamento , Adulto Jovem
5.
Gene ; 737: 144411, 2020 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-32006596

RESUMO

Long non-coding RNAs (lncRNAs) have been identified in cerebral ischemia-reperfusion (I/R) injury nowadays. Herein, we uncovered the function and underlying mechanism of the lncRNA Rian in cerebral I/R injury. The oxygen-glucose deprivation model in N2a cells was offered to mimic cerebral I/R injury in vitro. Trypan blue staining, reactive oxygen species (ROS) production, and caspase-3 activity were used to evaluate cell apoptosis. Then, middle cerebral artery occlusion was conducted to evaluate the function of lncRNA Rian in mice. Real-time PCR and western blotting were performed to determine the expression of lncRNA Rian, miR-144-3p, GATA binding protein 3 (GATA3), caspase-3, Bax, and Bcl-2. The results showed that both Rian and GATA3 were downregulated, and miR-144-3p was upregulated in cerebral I/R injury in vitro and in vivo. Overexpression of Rian could inhibit the cell apoptosis induced by oxygen-glucose deprivation. Furthermore, overexpression of Rian distinctly reduced the infarct size, and it also improved the neurological score. Overexpression of Rian could abolish miR-144-3p-mediated I/R injury in vitro and in vivo. Besides, GATA3 was the target of miR-144-3p and GATA3 could be regulated co-operatively by miR-144-3p and Rian. Consequently, these findings showed that the Rian/miR-144-3p/GATA3 axis is an essential signaling in cerebral I/R injury. The lncRNA Rian may serve as a potential target for novel treatment in patients with ischemic stroke.

6.
Mucosal Immunol ; 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-32020030

RESUMO

Intestinal fibrosis leading to strictures remains a significant clinical problem in inflammatory bowel diseases (IBD). The role of bacterial components in activating intestinal mesenchymal cells and driving fibrogenesis is largely unexplored. Tamoxifen-inducible α-SMA promoter Cre mice crossed with floxed MyD88 mice were subjected to chronic dextran sodium sulfate colitis. MyD88 was deleted prior to or after induction of colitis. Human intestinal myofibroblasts (HIMF) were exposed to various bacterial components and assessed for fibronectin (FN) and collagen I (Col1) production. RNA sequencing was performed. Post-transcriptional regulation was assessed by polysome profiling assay. Selective deletion of MyD88 in α-SMA-positive cells prior to, but not after induction of, experimental colitis decreased the degree of intestinal fibrosis. HIMF selectively responded to flagellin with enhanced FN or Col1 protein production in a MyD88-dependent manner. RNA sequencing suggested minimal transcriptional changes induced by flagellin in HIMF. Polysome profiling revealed higher proportions of FN and Col1 mRNA in the actively translated fractions of flagellin exposed HIMF, which was mediated by eIF2 alpha and 4EBP1. In conclusion, selectivity of flagellin-induced ECM secretion in HIMF is post-transcriptionally regulated. The results may represent a novel and targetable link between the gut microbiota and intestinal fibrogenesis.

7.
Opt Lett ; 45(5): 1112-1115, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-32108783

RESUMO

A low voltage operation electro-optic modulator is critical for applications ranging from optical communications to an analog photonic link. This paper reports a hybrid silicon nitride and lithium niobate electro-optic Mach-Zehnder modulator that employs 3 dB multimode interference couplers for splitting and combining light. The presented amplitude modulator with an interaction region length of 2.4 cm demonstrates a DC half-wave voltage of only 0.875 V, which corresponds to a modulation efficiency per unit length of 2.11 V cm. The power extinction ratio of the fabricated device is approximately 30 dB, and the on-chip optical loss is about 5.4 dB.

8.
Molecules ; 25(2)2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31952217

RESUMO

Unique tunable aryl imidazolium ionic liquids successfully catalyzed Friedel-Crafts acylation and thioesterification in sealed tubes. These reactions can form a C-C bond and a C-S bond with high atom economy. Ionic liquids exhibited high activity and catalyzed essential reactions with good to excellent yields while retaining their catalytic activities for recycling.

9.
Artigo em Inglês | MEDLINE | ID: mdl-31961286

RESUMO

Blue holes are unique geomorphological units characterized by steep redox and biogeochemical gradients. Yongle Blue Hole is located on the largest atoll (Yongle Atoll) of the western Xisha Islands in the South China Sea. A Gram-stain-negative, facultatively anaerobic, non-motile, non-flagellated marine bacterium with creamy white colonies, designated JC036T, was isolated from Yongle Blue Hole. Cells were short-rod-shaped and catalase-negative. 16S rRNA gene sequence analysis showed that sequence similarities were lower than 91.6 % against all validly named species in the family Prolixibacteraceae; a reconstructed phylogenetic tree indicated that strain JC036T formed a lineage with strains in the family Prolixibacteraceae. Growth occurred at 4-37 °C (optimum, 28 °C), at pH 5.0-9.0 (optimum, 7.0) and in the presence of 2-6 % (w/v) NaCl (optimum, 3 %). The prevalent isoprenoid quinone of strain JC036T was menaquinone-7 (MK-7). Iso-C15 : 0 and iso-C17 : 0 3-OH were the predominant fatty acids. The major polar lipids included a phospholipid, phosphatidylethanolamine, an aminophospholipid and four unidentified lipids. The genomic DNA G+C content of strain JC036T was 37.8 mol%. Based on physiological and biochemical characteristics and whole genome comparisons, we propose a new genus and species, Puteibacter caeruleilacunae gen. nov., sp. nov., within the family Prolixibacteraceae. The type strain of Puteibacter caeruleilacunae is JC036T (=JCM 33128T=MCCC 1K03579T). From this study, a deeper understanding of the community of the microorganism and their roles in biogeochemical cycles, especially anaerobic bacteria, is provided.

10.
Dalton Trans ; 49(5): 1375-1379, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-31935006

RESUMO

A novel discrete {Co14Mo24} nanoscale cluster, {CoIII2CoII10Cl2(dpbt)3(H2O)2[CoIIMoV12O31(CH3O)9]2}·24CH3OH (1) (here, dpbt = 5,5'-di(pyridin-2-yl)-3,3'-bi(1,2,4-triazole)), with a triangular Co4 core encapsulated in two novel capped Co-substituted Keggin-type Co5Mo12O40 anions, has been isolated from alkaline methanol solution. The high-resolution electrospray ionization mass spectrum (HRESI-MS) of microcrystalline 1 in MeOH/CH2Cl2 (v : v = 2 : 1) was recorded. Two prominent overlapping peaks in the range of m/z = 2740-2840 and 1820-1880 for the discrete fragments of [CoIII2CoII12MoV24O62Cl2(dpbt)3(H2O)2(CH3O)x(OH)18-x-2H]2- (x = 9-18, F1) and [CoIII2CoII12MoV24O62Cl2(dpbt)3(H2O)2(CH3O)x(OH)19-x-2H]3- (x = 6-13, F2), respectively, are obtained, confirming the {Co14Mo24} composition in 1. In addition, weak anti-ferromagnetic interactions in 1 are observed.

11.
Nature ; 577(7792): 641-646, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31996818

RESUMO

Memristor-enabled neuromorphic computing systems provide a fast and energy-efficient approach to training neural networks1-4. However, convolutional neural networks (CNNs)-one of the most important models for image recognition5-have not yet been fully hardware-implemented using memristor crossbars, which are cross-point arrays with a memristor device at each intersection. Moreover, achieving software-comparable results is highly challenging owing to the poor yield, large variation and other non-ideal characteristics of devices6-9. Here we report the fabrication of high-yield, high-performance and uniform memristor crossbar arrays for the implementation of CNNs, which integrate eight 2,048-cell memristor arrays to improve parallel-computing efficiency. In addition, we propose an effective hybrid-training method to adapt to device imperfections and improve the overall system performance. We built a five-layer memristor-based CNN to perform MNIST10 image recognition, and achieved a high accuracy of more than 96 per cent. In addition to parallel convolutions using different kernels with shared inputs, replication of multiple identical kernels in memristor arrays was demonstrated for processing different inputs in parallel. The memristor-based CNN neuromorphic system has an energy efficiency more than two orders of magnitude greater than that of state-of-the-art graphics-processing units, and is shown to be scalable to larger networks, such as residual neural networks. Our results are expected to enable a viable memristor-based non-von Neumann hardware solution for deep neural networks and edge computing.

12.
Circulation ; 141(3): 217-233, 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31801360

RESUMO

BACKGROUND: Heart failure is a leading cause of death worldwide. Cyclic nucleotide phosphodiesterases (PDEs), through degradation of cyclic nucleotides, play critical roles in cardiovascular biology and disease. Our preliminary screening studies have revealed PDE10A upregulation in the diseased heart. However, the roles of PDE10A in cardiovascular biology and disease are largely uncharacterized. The current study is aimed to investigate the regulation and function of PDE10A in cardiac cells and in the progression of cardiac remodeling and dysfunction. METHODS: We used isolated adult mouse cardiac myocytes and fibroblasts, as well as preclinical mouse models of hypertrophy and heart failure. The PDE10A selective inhibitor TP-10, and global PDE10A knock out mice were used. RESULTS: We found that PDE10A expression remains relatively low in normal and exercised heart tissues. However, PDE10A is significantly upregulated in mouse and human failing hearts. In vitro, PDE10A deficiency or inhibiting PDE10A with selective inhibitor TP-10, attenuated cardiac myocyte pathological hypertrophy induced by Angiotensin II, phenylephrine, and isoproterenol, but did not affect cardiac myocyte physiological hypertrophy induced by IGF-1 (insulin-like growth factor 1). TP-10 also reduced TGF-ß (transforming growth factor-ß)-stimulated cardiac fibroblast activation, proliferation, migration and extracellular matrix synthesis. TP-10 treatment elevated both cAMP and cGMP levels in cardiac myocytes and cardiac fibroblasts, consistent with PDE10A as a cAMP/cGMP dual-specific PDE. In vivo, global PDE10A deficiency significantly attenuated myocardial hypertrophy, cardiac fibrosis, and dysfunction induced by chronic pressure overload via transverse aorta constriction or chronic neurohormonal stimulation via Angiotensin II infusion. Importantly, we demonstrated that the pharmacological effect of TP-10 is specifically through PDE10A inhibition. In addition, TP-10 is able to reverse pre-established cardiac hypertrophy and dysfunction. RNA-Sequencing and bioinformatics analysis further identified a PDE10A-regualted transcriptome involved in cardiac hypertrophy, fibrosis, and cardiomyopathy. CONCLUSIONS: Taken together, our study elucidates a novel role for PDE10A in the regulation of pathological cardiac remodeling and development of heart failure. Given that PDE10A has been proven to be a safe drug target, PDE10A inhibition may represent a novel therapeutic strategy for preventing and treating cardiac diseases associated with cardiac remodeling.

13.
Cytokine ; 126: 154871, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31629104

RESUMO

OBJECTIVE: Chronic activation of the innate immune system plays a central role in HIV-1 disease progression. Negative regulation of innate immunity is critical in preventing the effects of this excessive activation; however, the molecules involved in this process remain to be identified. In this study, we compared the expression of immune regulation genes between HIV-1 infected individuals and healthy control participants to identify genes involved in the regulation of innate immunity in HIV-1 infection. METHODS: We conducted gene expression analysis of a series of immune regulatory genes in viremic treatment-naïve HIV-positive donors, patients receiving highly active antiretroviral therapy (HAART) and HIV-negative healthy control participants. Reverse transcription-quantitative PCR (RT-qPCR) was conducted to determine the expression levels of genes in peripheral blood mononuclear cells isolated from all participants. The spearman correlation test and linear regression analysis were performed to evaluate the correlation between gene expression level and viral load. RESULTS: The following differentially expressed genes were identified: A20, CYLD, DDX24, MARCH5, MKRN2, PTP1B, RNF125, S1PR1, SOCS1, IFI35, RBCK1, TTLL12 and USP18. The three most differentially expressed genes were A20, S1PR1, and USP18. USP18 correlated positively with viral load. CONCLUSION: Thirteen immune regulation genes were identified in comparisons of viremic treatment-naïve HIV-positive donors, HAART-treated patients and healthy control participants, indicating the potential of these genes as therapeutic targets.

14.
Sci Rep ; 9(1): 19026, 2019 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-31836750

RESUMO

BEST1 is a Ca2+-activated Cl- channel predominantly expressed in retinal pigment epithelium (RPE), and over 250 genetic mutations in the BEST1 gene have been identified to cause retinal degenerative disorders generally known as bestrophinopathies. As most BEST1 mutations are autosomal dominant, it is of great biomedical interest to determine their disease-causing mechanisms and the therapeutic potential of gene therapy. Here, we characterized six Best vitelliform macular dystrophy (BVMD)-associated BEST1 dominant mutations by documenting the patients' phenotypes, examining the subcellular localization of endogenous BEST1 and surface Ca2+-dependent Cl- currents in patient-derived RPEs, and analyzing the functional influences of these mutations on BEST1 in HEK293 cells. We found that all six mutations are loss-of-function with different levels and types of deficiencies, and further demonstrated the restoration of Ca2+-dependent Cl- currents in patient-derived RPE cells by WT BEST1 gene supplementation. Importantly, BEST1 dominant and recessive mutations are both rescuable at a similar efficacy by gene augmentation via adeno-associated virus (AAV), providing a proof-of-concept for curing the vast majority of bestrophinopathies.

15.
Huan Jing Ke Xue ; 40(11): 5024-5031, 2019 Nov 08.
Artigo em Chinês | MEDLINE | ID: mdl-31854570

RESUMO

Wastewater treatment plants (WWTPs) are regarded as the main source for antibiotic resistant genes (ARGs). To explore the features regarding the distribution of ARGs in wastewater with complicated composition in treatment plants, wastewater samples from a chemical industry park that produced antibiotics were selected. qPCR was applied to detect the type and abundance of ARGs in the wastewater flows from the WWTPs. The results indicated that 16 types of ARGs were detected from the wastewater from the WWTPs, among which sulfonamide resistance genes and tetracycline resistance genes were the dominant ARGs that appeared in the wastewater. Additionally, intI 1 was detected and its abundance was correlated with that of sulfonamide resistance genes. This indicated that intI 1 may promote the migration and transformation of sulfonamide resistance genes. The pharmaceutical factories in the park mainly synthesize macrolide antibiotics. Because of the selective pressure, the absolute abundance of ermB in the wastewater was much higher than that in the other industrial wastewater. The total ARGs decreased by 1.16 log via traditional biological treatment process, and the total ARGs decreased by 2.46 log via the Fenton process. The results showed that the removal effects of deep treatment processes on ARGs were better than that of biological treatment in this wastewater treatment process. Highly abundant and movable ARGs already exist in the water body, and their release from WWTPs without effective treatment poses high risks to the environment.


Assuntos
Antibacterianos , Resistência Microbiana a Medicamentos , Águas Residuárias , Resistência Microbiana a Medicamentos/genética , Genes Bacterianos , Eliminação de Resíduos Líquidos
16.
Chaos ; 29(10): 103144, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31675807

RESUMO

Controlling human brain networks has aroused wide interest recently, where structural controllability provides powerful tools to unveil the relationship between its structure and functions. In this article, we define the optimal control signal path where the external control signal flows from one node to other nodes in the network. The control signal path not only shows the connections of some specific nodes in the brain network and the functions but also helps us to have a better understanding of how the control signals select and pass through the nodes to enable the brain functions with the minimum control energy. In common cases, as the control signal located on different nodes and the possible permutations of the nodes en route, there are enormous numbers of potential control signal paths in the network. The efficiency of a control signal path is defined to evaluate the most important path of the network based on the control energy. We propose the algorithms using control centrality to find the most effective control signal paths under several cases of prerequisites. As the human brain functional networks could be divided into several subnetworks to accomplish different cognition tasks (such as visuality and auditory), by the local control centrality of nodes, we could select the control signal path more efficiently, which might lead to unveiling the potential neural pathway to accomplish cognition progress.

17.
Comput Struct Biotechnol J ; 17: 1326-1338, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31741723

RESUMO

Alteration of RNA structure by environmental signals is a fundamental mechanism of gene regulation. For example, the riboswitch is a noncoding RNA regulatory element that binds a small molecule and causes a structural change in the RNA, thereby regulating transcription, splicing, or translation of an mRNA. The role of riboswitches in metabolite sensing and gene regulation in bacteria and other lower species was reported almost two decades ago, but riboswitches have not yet been discovered in mammals. An analog of the riboswitch, the protein-directed RNA switch (PDRS), has been identified as an important regulatory mechanism of gene expression in mammalian cells. RNA-binding proteins and microRNAs are two major executors of PDRS via their interaction with target transcripts in mammals. These protein-RNA interactions influence cellular functions by integrating environmental signals and intracellular pathways from disparate stimuli to modulate stability or translation of specific mRNAs. The discovery of a riboswitch in eukaryotes that is composed of a single class of thiamine pyrophosphate (TPP) suggests that additional ligand-sensing RNAs may be present to control eukaryotic or mammalian gene expression. In this review, we focus on protein-directed RNA switch mechanisms in mammals. We offer perspectives on the potential discovery of mammalian protein-directed and compound-dependent RNA switches that are related to human disease and medicine.

18.
J Clin Med ; 8(11)2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31731708

RESUMO

BACKGROUND: Malnutrition and inflammation are highly prevalent and tightly regulated with each other in chronic kidney disease (CKD) patients. Inflammation can lead to malnutrition in patients with sufficient nourishment, while malnutrition may also induce an inflammatory response. This study investigated whether the albumin-globulin ratio (AGR) can predict the mortality risk in CKD patients. METHODS: We enrolled 956 stage 3-5 CKD patients retrospectively at a medical center. Patients' baseline characteristics including demographics, laboratory data, pharmacotherapy, and comorbidities were collected for statistical adjustments. The study patients were stratified into three AGR groups according to similar magnitudes of hazards for mortality as follows: low AGR group, AGR ≤ 1.0; moderate AGR group, 1.1 ≤ AGR < 1.3; high AGR group, AGR ≥1.3. Multivariate Cox proportional hazard analysis was performed to evaluate the association of the AGR with the study outcomes, including overall and cardiovascular disease (CVD) mortality. RESULTS: During a median follow-up duration of 2.44 years, 108 (11.3%) deaths were recorded and 50 patients died from CVD. In adjusted model 1, the moderate AGR group was associated with hazard ratios (HR) of 0.57 (95% CI = 0.36-0.90, p = 0.016) and 0.52 (95% CI = 0.28-0.98, p = 0.043) for all-cause and CVD mortality compared with the low AGR group, respectively. The high AGR group was associated with HRs of 0.49 (95% CI = 0.27-0.90, p = 0.021) and 0.27 (95% CI = 0.1-0.74, p = 0.01) for all-cause and CVD mortality compared with the low AGR group, respectively. Similar results were obtained in the adjusted model 2 (inverse probability of the group weighted Cox model). In addition, the association between the AGR and mortality risk remained significant when the AGR was treated as a continuous variable. CONCLUSION: AGR is a significant biomarker predicting overall and cardiovascular mortality risk independent of various important factors amongst stage 3-5 CKD patients. We suggest that the AGR may be a simple and inexpensive measurement for detecting CKD patients at risk of mortality.

19.
Zhongguo Zhong Yao Za Zhi ; 44(16): 3423-3428, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31602904

RESUMO

To investigate the effect of triptolide on cognitive dysfunction in vascular dementia rats and its effect on SIRT1/NF-κB pathway,fifty healthy male Sprague-Dawley rats were randomly divided into 5 groups: Sham operation group( Sham group),vascular dementia model group( 2 VO group),triptolide intraperitoneal injection group( TR group),triptolide intraperitoneal injection + EX527 intracerebroventricular administration group( T+E group),EX527 intracerebroventricular administration group( EX527 group). After 4 weeks of modeling,Morris water maze test and object recognition test were used to evaluate the learning and memory ability of rats. The morphological changes of hippocampus in each group were observed in brain tissue. The chemical colorimetry was used to detect the activities of SOD and MDA in hippocampus. IL-6 and TNF-α levels were detected by ELISA. Western blot was used to detect the expression of SIRT1,NF-κB,IκBα and caspase 3 in hippocampus. The results showed that compared with the Sham group,the learning and memory ability of the vascular dementia model rats was reduced,the SOD activity in the hippocampus was decreased,the MDA activity and IL-6 level were increased,the neuronal degeneration changed significantly,the expression of SIRT1 and IκBα was decreased and the expression of caspase 3 and NF-κB was significantly increased. After intervention by triptolide,the level of oxidative stress and the degenerative changes in hippocampus were significantly slowed down. The expression of SIRT1 and IκBα protein was increased and the expression of caspase 3 and NF-κB was significantly decreased. While,after intervention by triptolide and EX527,the expression of SIRT1 was decreased,the levels of oxidative stress and neuronal degeneration in the hippocampus were aggravated,and the learning and memory ability was reduced. The results showed that triptolide could improve cognitive impairment in vascular dementia rats and its mechanism may be related to SIRT1/NF-κB signaling pathway.


Assuntos
Disfunção Cognitiva/tratamento farmacológico , Demência Vascular/tratamento farmacológico , Diterpenos/farmacologia , NF-kappa B/metabolismo , Fenantrenos/farmacologia , Transdução de Sinais , Sirtuína 1/metabolismo , Animais , Compostos de Epóxi/farmacologia , Hipocampo/efeitos dos fármacos , Masculino , Estresse Oxidativo , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley
20.
Sci Rep ; 9(1): 13694, 2019 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-31548559

RESUMO

The emergence of drug-resistant fungal pathogens is becoming increasingly serious due to overuse of antifungals. Antimicrobial peptides have potent activity against a broad spectrum of pathogens, including fungi, and are considered a potential new class of antifungals. In this study, we examined the activities of the newly designed peptides P-113Du and P-113Tri, together with their parental peptide P-113, against the human fungal pathogen Candida albicans. The results showed that these peptides inhibit mitochondrial complex I, specifically NADH dehydrogenase, of the electron transport chain. Moreover, P-113Du and P-113Tri also block alternative NADH dehydrogenases. Currently, most inhibitors of the mitochondrial complex I are small molecules or artificially-designed antibodies. Here, we demonstrated novel functions of antimicrobial peptides in inhibiting the mitochondrial complex I of C. albicans, providing insight in the development of new antifungal agents.

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