Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 342
Filtrar
1.
Artigo em Inglês | MEDLINE | ID: mdl-34507817

RESUMO

OBJECTIVE: Calcified aortic valvular disease is known as an inflammation-related process related to force. The purpose of this study was to determine whether micromechanical force could induce valve calcification of porcine valvular interstitial cells and to examine the role of integrin αvß3 in valvular calcification by using a novel method: magnetic twisting cytometry. METHODS: Porcine valvular interstitial cells were cultured in vitro, and micromechanical force was applied to porcine valvular interstitial cells using magnetic twisting cytometry. Changes in calcification-related factors osteopontin and RUNX2 were detected. By using the calcification medium, the optimal magnetic twisting cytometry parameters for inducing valvular interstitial cell calcification were determined, and a magnetic twisting cytometry calcification promotion model was established. The role of αvß3 in calcification was studied by using αvß3 antagonists to block the function of αvß3. RESULTS: Reverse transcription polymerase chain reaction assays showed that the expression of osteopontin was enhanced 30 minutes after 25G-1Hz 5 minutes of stimulation. Western blotting assays showed that the expression of osteopontin and RUNX2 was upregulated 24 hours after 25G-1Hz 5 minutes of stimulation. The optimal magnetic twisting cytometry parameter for inducing porcine valvular interstitial cell calcification was 25G-2Hz for 10 minutes. The expression of osteopontin and RUNX2 decreased significantly after the addition of αvß3 antagonist. Clinically, patients with bicuspid aortic valves had high expression of RUNX2 and ß3 in the aortic valve, and ß3 significantly correlated with RUNX2. CONCLUSIONS: By using magnetic twisting cytometry, we established a porcine valvular interstitial cell calcification model by micromechanical force stimulation and obtained the optimal parameters. Integrin αvß3 plays a key role in the aortic valve calcification process.

2.
Sci Rep ; 11(1): 17858, 2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34504199

RESUMO

Protein lysine acetylation (Kac) is an important post-translational modification in both animal and plant cells. Global Kac identification has been performed at the proteomic level in various species. However, the study of Kac in oil and resource plant species is relatively limited. Soybean is a globally important oil crop and resouce plant. In the present study, lysine acetylome analysis was performed in soybean leaves with proteomics techniques. Various bioinformatics analyses were performed to illustrate the structure and function of these Kac sites and proteins. Totally, 3148 acetylation sites in 1538 proteins were detected. Motif analysis of these Kac modified peptides extracted 17 conserved motifs. These Kac modified protein showed a wide subcellular location and functional distribution. Chloroplast is the primary subcellular location and cellular component where Kac proteins were localized. Function and pathways analyses indicated a plenty of biological processes and metabolism pathways potentially be influenced by Kac modification. Ribosome activity and protein biosynthesis, carbohydrate and energy metabolism, photosynthesis and fatty acid metabolism may be regulated by Kac modification in soybean leaves. Our study suggests Kac plays an important role in soybean physiology and biology, which is an available resource and reference of Kac function and structure characterization in oil crop and resource plant, as well as in plant kingdom.

3.
Nature ; 2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34587621

RESUMO

The transition-metal kagome lattice materials host frustrated, correlated, and topological quantum states of matter1-9. Recently, a new family of vanadium-based kagome metals AV3Sb5 (A=K, Rb, and Cs) with topological band structures has been discovered10,11. These layered compounds are nonmagnetic and undergo charge density wave transitions before developing superconductivity at low temperatures11-19. Here we report the observation of unconventional superconductivity and pair density wave (PDW) in CsV3Sb5 using scanning tunneling microscope/spectroscopy (STM/STS) and Josephson STS. We find that CsV3Sb5 exhibits a V-shaped pairing gap Δ~0.5 meV and is a strong-coupling superconductor (2∆/kBTc~5) that coexists with 4a0 unidirectional and 2a0×2a0 charge order. Remarkably, we discover a 3Q PDW accompanied by bidirectional 4a0/3 spatial modulations of the superconducting gap, coherence peak and gap-depth in the tunneling conductance. We term this novel quantum state a roton-PDW associated with an underlying vortex-antivortex lattice that can account for the observed conductance modulations. Probing the electronic states in the vortex halo in an applied magnetic field, in strong-field that suppresses superconductivity, and in zero-field above Tc reveals that the PDW is a primary state responsible for an emergent pseudogap and intertwined electronic order. Our findings show striking analogies and distinctions to the phenomenology of high-Tc cuprate superconductors, and provide groundwork for understanding the microscopic origin of correlated electronic states and superconductivity in vanadium-based kagome metals.

4.
BMJ Open ; 11(8): e049902, 2021 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-34426467

RESUMO

INTRODUCTION: The full-endoscopic spinal surgery (FESS) procedure is widely accepted and welcomed in China. With the continuous development of minimally invasive surgery, the further expansion of indications and the greater diversity of techniques, spinal endoscopic surgery currently accounts for more than 10% of spinal surgery in China, ranking among the top in the world. However, the admission system and standardised training system for spinal endoscopic surgery are not perfect, which presents a challenge and disadvantage for novices. METHODS AND ANALYSIS: Exploratory mixed methods are applied for designing this study. First, we will collect questions from novices by allowing them to openly list their concerns to those who have completed FESS. These qualitative questions will be categorised using NVivo software. To produce the qualitative results, a questionnaire for the sequential two-round Delphi approach will be developed to identify the 20 most important questions from novices. This study is planned to be started at April 2021, and completed at March 2022. ETHICS AND DISSEMINATION: The Research Ethics Committee of Peking University Third Hospital provided a waiver for this Delphi protocol. We expect that the findings will be published in a clinical journal and presented at conferences. Furthermore, we hope that the results can contribute to answering the questions raised by novices of spinal endoscopy in the form of books and to improving the training system for spinal endoscopy surgery.


Assuntos
Endoscopia , Projetos de Pesquisa , China , Humanos , Procedimentos Neurocirúrgicos , Inquéritos e Questionários
5.
Nat Commun ; 12(1): 4664, 2021 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-34341353

RESUMO

Excessive inflammatory responses induced upon SARS-CoV-2 infection are associated with severe symptoms of COVID-19. Inflammasomes activated in response to SARS-CoV-2 infection are also associated with COVID-19 severity. Here, we show a distinct mechanism by which SARS-CoV-2 N protein promotes NLRP3 inflammasome activation to induce hyperinflammation. N protein facilitates maturation of proinflammatory cytokines and induces proinflammatory responses in cultured cells and mice. Mechanistically, N protein interacts directly with NLRP3 protein, promotes the binding of NLRP3 with ASC, and facilitates NLRP3 inflammasome assembly. More importantly, N protein aggravates lung injury, accelerates death in sepsis and acute inflammation mouse models, and promotes IL-1ß and IL-6 activation in mice. Notably, N-induced lung injury and cytokine production are blocked by MCC950 (a specific inhibitor of NLRP3) and Ac-YVAD-cmk (an inhibitor of caspase-1). Therefore, this study reveals a distinct mechanism by which SARS-CoV-2 N protein promotes NLRP3 inflammasome activation and induces excessive inflammatory responses.


Assuntos
COVID-19/metabolismo , Proteínas do Nucleocapsídeo de Coronavírus/metabolismo , Inflamassomos/metabolismo , Inflamação/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , SARS-CoV-2/metabolismo , Animais , COVID-19/virologia , Células Cultivadas , Citocinas/metabolismo , Células HEK293 , Humanos , Inflamassomos/genética , Lesão Pulmonar/genética , Lesão Pulmonar/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Fosfoproteínas/metabolismo , Ligação Proteica , SARS-CoV-2/fisiologia , Células THP-1
6.
Int J Mol Sci ; 22(16)2021 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-34445274

RESUMO

Modification of the human genome has immense potential for preventing or treating disease. Modern genome editing techniques based on CRISPR/Cas9 show great promise for altering disease-relevant genes. The efficacy of precision editing at CRISPR/Cas9-induced double-strand breaks is dependent on the relative activities of nuclear DNA repair pathways, including the homology-directed repair and error-prone non-homologous end-joining pathways. The competition between multiple DNA repair pathways generates mosaic and/or therapeutically undesirable editing outcomes. Importantly, genetic models have validated key DNA repair pathways as druggable targets for increasing editing efficacy. In this review, we highlight approaches that can be used to achieve the desired genome modification, including the latest progress using small molecule modulators and engineered CRISPR/Cas proteins to enhance precision editing.


Assuntos
Sistemas CRISPR-Cas , Quebras de DNA de Cadeia Dupla , Reparo do DNA por Junção de Extremidades , Edição de Genes , Modelos Genéticos , Reparo de DNA por Recombinação , Animais , Humanos
7.
Mol Imaging ; 2021: 9996125, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34381316

RESUMO

Background: Inducible nitric oxide synthase (iNOS) plays a crucial role in neuroinflammation, especially microglial activity, and may potentially represent a useful biomarker of neuroinflammation. In this study, we carefully defined a strategic plan to develop iNOS-targeted molecular PET imaging using (4'-amino-5',8'-difluoro-1'H-spiro[piperidine-4,2'-quinazolin]-1-yl)(4-fluorophenyl)methanone ([18F]FBAT) as a tracer in a mouse model of lipopolysaccharide- (LPS-) induced brain inflammation. Methods: An in vitro model, murine microglial BV2 cell line, was used to assess the uptake of [18F]FBAT in response to iNOS induction at the cellular level. In vivo whole-body dynamic PET/MR imaging was acquired in LPS-treated (5 mg/kg) and control mice. Standard uptake value (SUV), total volume of distribution (V t), and area under the curve (AUC) based on the [18F]FBAT PET signals were determined. The expression of iNOS was confirmed by immunohistochemistry (IHC) of brain tissues. Results: At the end of synthesis, the yield of [18F]FBAT was 2.2-3.1% (EOS), radiochemical purity was >99%, and molar radioactivity was 125-137 GBq/µmol. In vitro, [18F]FBAT rapidly and progressively accumulated in murine microglial BV2 cells exposed to LPS; however, [18F]FBAT accumulation was inhibited by aminoguanidine, a selective iNOS inhibitor. In vivo biodistribution studies of [18F]FBAT showed a significant increase in the liver and kidney on LPS-treated mice. At 3 h postinjection of LPS, in vivo, the [18F]FBAT accumulation ratios at 30 min post intravenous (i.v.) radiotracer injection for the whole brain, cortex, cerebellum, and brainstem were 2.16 ± 0.18, 1.53 ± 0.25, 1.41 ± 0.21, and 1.90 ± 0.12, respectively, compared to those of mice not injected with LPS. The mean area under the curve (AUC0-30min), total volume of distribution (V t, mL/cm3), and K i (influx rate) of [18F]FBAT were 1.9 ± 0.21- and 1.4 ± 0.22-fold higher in the 3 h LPS group, respectively, than in the control group. In the pharmacokinetic two-compartment model, the whole brain K i of [18F]FBAT was significantly higher in mice injected with LPS compared to the control group. Aminoguanidine, selective iNOS inhibitor, pretreatment significantly reduced the AUC0-30min and V t values in LPS-induced mice. Quantitative analysis of immunohistochemically stained brain sections confirmed iNOS was preferentially upregulated in the cerebellum and cortex of mice injected with LPS. Conclusion: An automated robotic method was established for radiosynthesis of [18F]FBAT, and the preliminary in vitro and in vivo results demonstrated the feasibility of detecting iNOS activity/expression in LPS-treated neuroinflammation by noninvasive imaging with [18F]FBAT PET/MRI.

8.
J Org Chem ; 86(17): 11771-11781, 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34338508

RESUMO

Litosetoenins A-E (1-5), five new ring-rearranged serrulatane-type diterpenoids with a common tricyclo[3.0.4]decane core, along with a known diterpenoid glycoside (6), a related known diterpenoid (7), and four known sesquiterpenoids (8-11), were isolated from a Balinese soft coral Litophyton setoensis. Spirolitosetoenin A (5a) and isospirolitosetoenin A (5b), featuring an unprecedented spiro[4,5]decane core, were obtained after treatment of compound 5 with HCl in methanol. The structures of new compounds were elucidated by extensive spectroscopic analysis, quantum mechanical nuclear magnetic resonance approach, and chemical methods. A plausible biosynthetic pathway involving an unusual divergent biogenesis was proposed.

9.
Neurosci Bull ; 2021 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-34235622

RESUMO

Sodium salicylate is an anti-inflammatory medication with a side-effect of tinnitus. Here, we used mouse cochlear cultures to explore the effects of salicylate treatment on cochlear inner hair cells (IHCs). We found that IHCs showed significant damage after exposure to a high concentration of salicylate. Whole-cell patch clamp recordings showed that 1-5 mmol/L salicylate did not affect the exocytosis of IHCs, indicating that IHCs are not involved in tinnitus generation by enhancing their neuronal input. Instead, salicylate induced a larger peak amplitude, a more negative half-activation voltage, and a steeper slope factor of Ca2+ current. Using noise analysis of Ca2+ tail currents and qRT-PCR, we further found that salicylate increased the number of Ca2+ channels along with CaV1.3 expression. All these changes could act synergistically to enhance the Ca2+ influx into IHCs. Inhibition of intracellular Ca2+ overload significantly attenuated IHC death after 10 mmol/L salicylate treatment. These results implicate a cellular mechanism for tinnitus generation in the peripheral auditory system.

10.
J Control Release ; 337: 132-143, 2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34284047

RESUMO

Ovarian cancer has the highest mortality rate among all gynecologic malignancies. HER2+ ovarian cancer is a subtype that is aggressive and associated with metastasis to distant sites such as the lungs. Therefore, accurate biological characterization of metastatic lesions is vital as it helps physicians select the most effective treatment strategy. Functional imaging of ovarian cancer with PET/CT is routinely used in the clinic to detect metastatic disease and evaluate treatment response. However, this imaging method does not provide information regarding the presence or absence of cancer-specific cell surface biomarkers such as HER2. As a result, this method does not help physicians decide whether to choose immunotherapy to treat metastasis. To differentiate the HER2+ from HER2¯ lesions in ovarian cancer lung metastasis, AbX50C4:Gd vector composed of a HER2 targeting affibody and XTEN peptide was genetically engineered. It was then labeled with gadolinium (Gd) via a stable linker. The vector was characterized physicochemically and biologically to determine its purity, molecular weight, hydrodynamic size and surface charge, stability in serum, endotoxin levels, relaxivity and ability to target the HER2 antigen. Then, SCID mice were implanted with SKOV-3 (HER2+) and OVASC-1 (HER2¯) tumors in the lungs and injected with the Gd-labeled HER2 targeted AbX50C4:Gd vector. The mice were imaged using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), followed by R1-mapping and quantitative analysis of the images. Our data demonstrate that the developed HER2-targeted vector can differentiate HER2+ lung metastasis from HER2¯ lesions using DCE-MRI. The developed vector could potentially be used in conjunction with other imaging modalities to prescreen patients and identify candidates for immunotherapy while triaging those who may not be considered responsive.

11.
PLoS Pathog ; 17(7): e1008603, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34310658

RESUMO

Dengue virus (DENV) is a mosquito-borne pathogen that causes a spectrum of diseases including life-threatening dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Vascular leakage is a common clinical crisis in DHF/DSS patients and highly associated with increased endothelial permeability. The presence of vascular leakage causes hypotension, circulatory failure, and disseminated intravascular coagulation as the disease progresses of DHF/DSS patients, which can lead to the death of patients. However, the mechanisms by which DENV infection caused the vascular leakage are not fully understood. This study reveals a distinct mechanism by which DENV induces endothelial permeability and vascular leakage in human endothelial cells and mice tissues. We initially show that DENV2 promotes the matrix metalloproteinase-9 (MMP-9) expression and secretion in DHF patients' sera, peripheral blood mononuclear cells (PBMCs), and macrophages. This study further reveals that DENV non-structural protein 1 (NS1) induces MMP-9 expression through activating the nuclear factor κB (NF-κB) signaling pathway. Additionally, NS1 facilitates the MMP-9 enzymatic activity, which alters the adhesion and tight junction and vascular leakage in human endothelial cells and mouse tissues. Moreover, NS1 recruits MMP-9 to interact with ß-catenin and Zona occludens protein-1/2 (ZO-1 and ZO-2) and to degrade the important adhesion and tight junction proteins, thereby inducing endothelial hyperpermeability and vascular leakage in human endothelial cells and mouse tissues. Thus, we reveal that DENV NS1 and MMP-9 cooperatively induce vascular leakage by impairing endothelial cell adhesion and tight junction, and suggest that MMP-9 may serve as a potential target for the treatment of hypovolemia in DSS/DHF patients.

12.
Sci Adv ; 7(27)2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34215591

RESUMO

Transmission-blocking vaccines are urgently needed to reduce transmission of SARS-CoV 2, the cause of the COVID-19 pandemic. The upper respiratory tract is an initial site of SARS-CoV-2 infection and, for many individuals, remains the primary site of virus replication. An ideal COVID-19 vaccine should reduce upper respiratory tract virus replication and block transmission as well as protect against severe disease. Here, we optimized a vaccine candidate, parainfluenza virus 5 (PIV5) expressing the SARS-CoV-2 S protein (CVXGA1), and then demonstrated that a single-dose intranasal immunization with CVXGA1 protects against lethal infection of K18-hACE2 mice, a severe disease model. CVXGA1 immunization also prevented virus infection of ferrets and blocked contact transmission. This mucosal vaccine strategy inhibited SARS-CoV-2 replication in the upper respiratory tract, thus preventing disease progression to the lower respiratory tract. A PIV5-based mucosal vaccine provides a strategy to induce protective innate and cellular immune responses and reduce SARS-CoV-2 infection and transmission in populations.

13.
Neonatology ; 118(3): 373-377, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34148039

RESUMO

A preterm infant with birth weight 1,550 g had an intravenous foreign body between the external iliac vein and the common iliac vein, which accidentally happened during peripheral intravascular central catheter insertion by the Seldinger technique. The infant initially received conservative management and close monitoring. Antibiotics were administered 4 weeks to treat culture positive sepsis and meningitis. The infant was clinically stable till the cannula fragment migrated to the heart 34 days later. At that time, his weight was 2,200 g, and he was full fed. The cannula fragment was retrieved by emergency interventional radiology via the right femoral access, with no complications. The infant was discharged at 45 days of age and closely followed up post-discharge. He is currently 6 months old, with normal development. This is the first case of successful percutaneous retrieval of an intracardiac intravenous cannula fragment via femoral access in a premature infant in China.


Assuntos
Cânula , Cateterismo Venoso Central , Assistência ao Convalescente , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Masculino , Alta do Paciente
14.
Mol Ther ; 2021 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-34174443

RESUMO

Myosin VI(MYO6) is an unconventional myosin that is vital for auditory and vestibular function. Pathogenic variants in the human MYO6 gene cause autosomal-dominant or -recessive forms of hearing loss. Effective treatments for Myo6 mutation causing hearing loss are limited. We studied whether adeno-associated virus (AAV)-PHP.eB vector-mediated in vivo delivery of Staphylococcus aureus Cas9 (SaCas9-KKH)-single-guide RNA (sgRNA) complexes could ameliorate hearing loss in a Myo6WT/C442Y mouse model that recapitulated the phenotypes of human patients. The in vivo editing efficiency of the AAV-SaCas9-KKH-Myo6-g2 system on Myo6C442Y is 4.05% on average in Myo6WT/C442Y mice, which was ∼17-fold greater than editing efficiency of Myo6WT alleles. Rescue of auditory function was observed up to 5 months post AAV-SaCas9-KKH-Myo6-g2 injection in Myo6WT/C442Y mice. Meanwhile, shorter latencies of auditory brainstem response (ABR) wave I, lower distortion product otoacoustic emission (DPOAE) thresholds, increased cell survival rates, more regular hair bundle morphology, and recovery of inward calcium levels were also observed in the AAV-SaCas9-KKH-Myo6-g2-treated ears compared to untreated ears. These findings provide further reference for in vivo genome editing as a therapeutic treatment for various semi-dominant forms of hearing loss and other semi-dominant diseases.

15.
Antiviral Res ; 192: 105117, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34174248

RESUMO

In recent years, Zika virus (ZIKV), which causes severe diseases such as congenital microcephaly and Guillain-Barré syndrome, bringing serious harm to humans, has spread throughout the world. However, there are currently no effective drugs against the virus, and the need to develop anti-ZIKV drugs is thus urgent. In this study, we evaluated the antiviral efficacy of cinnamic acid against ZIKV by using reverse transcription-quantitative real-time PCR (qRT-PCR), plaque--forming, immunofluorescence and Western blotting. Additionally, Cinnamic acid possessed anti-ZIKV properties against the post-entry stage of the ZIKV replication cycle, and inhibited RdRp activity. In vivo, we found that cinnamic acid reduced the mortality of mice, viral load in the blood and ZIKV protein levels in the brain. Based on our experiments, cinnamic acid was found to be a potential effective anti-ZIKV drug.

16.
PLoS One ; 16(6): e0253325, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34138952

RESUMO

Lysine 2-hydroxyisobutyrylation (Khib) is a recently discovered post-translational modification (PTM) showing diverse biological functions and effects in living organisms. However, the study of Khib in plant species is still relatively limited. Wheat (Triticum aestivum L.) is a global important cereal plant. In this study, the systematic Khib analysis was performed in wheat leave tissues. A total of 3004 Khib sites in 1104 proteins were repeatedly identified. Structure characterization of these Khib peptides revealed 12 conserved sequence motifs. Function classification and enrichment analysis indicated these Khib proteins showed a wide function and pathway distribution, of which ribosome activity, protein biosynthesis and photosynthesis were the preferred biological processes. Subcellular location predication indicated chloroplast was the dominant subcellular compartment where Khib was distributed. There may be some crosstalks among Khib, lysine acetylation and lysine succinylation modification because some proteins and sites were modified by all these three acylations. The present study demonstrated the critical role of Khib in wheat biological and physiology, which has expanded the scope of Khib in plant species. Our study is an available resource and reference of Khib function demonstration and structure characterization in cereal plant, as well as in plant kingdom.

17.
Xenobiotica ; 51(7): 818-830, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33952086

RESUMO

Diabetes mellitus is a chronic metabolic disorder with multiple complications, patients who receive metformin may have a simultaneous intake of herbal medicine containing rutaecarpine due to cardiovascular protection and hypolipidemic effects of rutaecarpine. There might be drug interactions between metformin and rutaecarpine. This study aimed to investigate the effects of rutaecarpine on the pharmacodynamics and pharmacokinetics of metformin in diabetic rats.The diabetic rat model was induced with high-fat diet and low dose streptozotocin. Metformin with or without rutaecarpine was administered by oral gavage for 42 days. Pharmacodynamics and pharmacokinetics parameters were evaluated.The pharmacodynamics results revealed that co-administration of rutaecarpine with metformin resulted in a remarkable reduction of serum glucose and lipid profiles in diabetic rats compared to metformin treated alone. The pharmacokinetics results showed that co-treatments of rutaecarpine with metformin did not affect the systemic exposure and renal distribution of metformin, but increased metformin concentration in liver. Furthermore, rutaecarpine increased Oct1-mediated metformin uptake into hepatocytes by upregulation of Oct1 expression in the liver.The above data indicate that rutaecarpine enhanced the anti-diabetic effect of metformin, which may be associated with the increased hepatic distribution of metformin through up-regulation of Oct1 in response to rutaecarpine.


Assuntos
Diabetes Mellitus Experimental , Metformina , Animais , Diabetes Mellitus Experimental/tratamento farmacológico , Humanos , Hipoglicemiantes/farmacologia , Alcaloides Indólicos , Fígado , Metformina/farmacologia , Quinazolinas , Ratos , Regulação para Cima
18.
Skeletal Radiol ; 2021 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-34021773

RESUMO

OBJECTIVE: To evaluate the effect of intravenous (IV) contrast on sensitivity, specificity, and accuracy of magnetic resonance (MR) neurography of the knee with attention to the common peroneal nerve (CPN) in identifying nerve lesions and active muscle denervation changes. MATERIALS AND METHODS: A retrospective search for contrast-enhanced MR neurography cases evaluating the CPN at the knee was performed. Patients with electrodiagnostic testing (EDX) within 3 months of imaging were included and those with relevant prior surgery were excluded. Two radiologists independently reviewed non-contrast sequences and then 4 weeks later evaluated non-contrast and contrast sequences. McNemar's tests were performed to detect a difference between non-contrast only and combined non-contrast and contrast sequences in identifying nerve lesions and active muscle denervation changes using EDX as the reference standard. RESULTS: Forty-four exams in 42 patients (2 bilateral) were included. Twenty-eight cases had common peroneal neuropathy and 29, 21, and 9 cases had active denervation changes in the anterior, lateral, and posterior compartment/proximal muscles respectively on EDX. Sensitivity, specificity, and accuracy of non-contrast versus combined non-contrast and contrast sequences for common peroneal neuropathy were 50.0%, 56.2%, and 52.3% versus 50.0%, 56.2%, and 52.3% for reader 1 and 57.1%, 50.0%, and 54.5% versus 64.3%, 56.2%, and 61.4% for reader 2. Sensitivity, specificity, and accuracy of non-contrast and combined non-contrast and contrast sequences in identifying active denervation changes for anterior, lateral, and posterior compartment muscles were not significantly different. McNemar's tests were all negative. CONCLUSION: IV contrast does not improve the ability of MR neurography to detect CPN lesions or active muscle denervation changes.

19.
Biochem Biophys Res Commun ; 558: 71-78, 2021 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-33901926

RESUMO

Globally, type 2 diabetes (T2D) is the most common chronic disease. It affects approximately 500 million people worldwide. Dysregulation of the solute carrier family 2 member 4 (SLC2A4) gene and miR-335-5p has been associated with T2D progression. However, the mechanisms underlying this dysregulation are unclear. The levels of miR-335-5p and SLC2A4 in blood samples collected from patients with T2D (T2D blood samples) and pancreatic cell lines were measured by Real Time quantitative PCR (RT-qPCR). The relationship between miR-335-5p and SLC2A4 was investigated using a luciferase assay. The role of the miR-335-5p-SLC2A4 axis was detected by CCK8, BrdU, and caspase-3 assays in pancreatic cells treated with 25 mM glucose. Increased miR-335-5p and decreased SLC2A4 expression was observed in both T2D blood samples and pancreatic cell lines. The miR-335-5p mimic markedly suppressed proliferation and elevated apoptosis in glucose-treated pancreatic cells. SLC2A4 overexpression significantly enhanced proliferation but inhibited apoptosis in glucose-treated pancreatic cells. Moreover, miR-335-5p inhibited the expression of SLC2A4 in the pancreatic cells and suppressed the growth of these cells. The data indicated that miR-335-5p targeting of SLC2A4 could hamper the growth of T2D cell model by inhibiting their proliferation and elevating apoptosis. Collectively, our findings implicate miR-335-5p and SLC2A4 as potentially effective therapeutic targets for patients with T2D.


Assuntos
Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Transportador de Glucose Tipo 4/antagonistas & inibidores , Transportador de Glucose Tipo 4/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Apoptose/genética , Glicemia/metabolismo , Linhagem Celular , Proliferação de Células/genética , Diabetes Mellitus Tipo 2/etiologia , Regulação para Baixo , Redes Reguladoras de Genes , Glucose/farmacologia , Transportador de Glucose Tipo 4/metabolismo , Voluntários Saudáveis , Humanos , MicroRNAs/sangue , Pâncreas/citologia , Pâncreas/efeitos dos fármacos , Pâncreas/metabolismo , Mapas de Interação de Proteínas
20.
Phys Rev E ; 103(3-1): 032146, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33862756

RESUMO

Extracting equilibrium information from nonequilibrium measurements is a challenge task of great importance in understanding the thermodynamic properties of physical, chemical, and biological systems. The discovery of the Jarzynski equality illumines the way to estimate the equilibrium free-energy difference from the work performed in nonequilibrium driving processes. However, the nonlinear (exponential) relation causes the poor convergence of the Jarzynski equality. Here, we propose a concise method to estimate the free-energy difference through a linear nonequilibrium equality which inherently converges faster than nonlinear nonequilibrium equalities. This linear nonequilibrium equality relies on an accelerated isothermal process which is realized by using a unified variational approach, named variational shortcuts to isothermality. We apply our method to an underdamped Brownian particle moving in a double-well potential. The simulations confirm that the method can be used to accurately estimate the free-energy difference with high efficiency. Especially during fast driving processes with high dissipation, the method can improve the accuracy by more than an order of magnitude compared with the estimator based on the nonlinear nonequilibrium equality.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...