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1.
Ann Rheum Dis ; 2020 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-32205337

RESUMO

OBJECTIVES: Emerging evidence suggests that the microbiome plays an important role in the pathogenesis of osteoarthritis (OA). We aimed to test the two-hit model of OA pathogenesis and potentiation in which one 'hit' is provided by an adverse gut microbiome that activates innate immunity; the other 'hit' is underlying joint damage. METHODS: Medical history, faecal and blood samples were collected from human healthy controls (OA-METS-, n=4), knee OA without metabolic syndrome (OA+METS-, n=7) and knee OA with metabolic syndrome (OA+METS+, n=9). Each group of human faecal samples, whose microbial composition was identified by 16S rRNA sequencing, was pooled and transplanted into germ-free mice 2 weeks prior to meniscal/ligamentous injury (MLI) (n≥6 per group). Eight weeks after MLI, mice were evaluated for histological OA severity and synovitis, systemic inflammation and gut permeability. RESULTS: Histological OA severity following MLI was minimal in germ-free mice. Compared with the other groups, transplantation with the OA+METS+ microbiome was associated with higher mean systemic concentrations of inflammatory biomarkers (interleukin-1ß, interleukin-6 and macrophage inflammatory protein-1α), higher gut permeability and worse OA severity. A greater abundance of Fusobacterium and Faecalibaterium and lesser abundance of Ruminococcaceae in transplanted mice were consistently correlated with OA severity and systemic biomarkers concentrations. CONCLUSION: The study clearly establishes a direct gut microbiome-OA connection that sets the stage for a new means of exploring OA pathogenesis and potentially new OA therapeutics. Alterations of Fusobacterium, Faecalibaterium and Ruminococcaceae suggest a role of these particular microbes in exacerbating OA.

2.
Sensors (Basel) ; 20(6)2020 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-32168889

RESUMO

For multi-user uplink massive multiple input multiple output (MIMO) systems, minimum mean square error (MMSE) criterion-based linear signal detection algorithm achieves nearly optimal performance, on condition that the number of antennas at the base station is asymptotically large. However, it involves prohibitively high complexity in matrix inversion when the number of users is getting large. A low-complexity soft-output signal detection algorithm based on improved Kaczmarz method is proposed in this paper, which circumvents the matrix inversion operation and thus reduces the complexity by an order of magnitude. Meanwhile, an optimal relaxation parameter is introduced to further accelerate the convergence speed of the proposed algorithm and two approximate methods of calculating the log-likelihood ratios (LLRs) for channel decoding are obtained as well. Analysis and simulations verify that the proposed algorithm outperforms various typical low-complexity signal detection algorithms. The proposed algorithm converges rapidly and achieves its performance quite close to that of the MMSE algorithm with only a small number of iterations.

3.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 34(3): 362-366, 2020 Mar 15.
Artigo em Chinês | MEDLINE | ID: mdl-32174084

RESUMO

Objective: To study the expressions of Renin, angiotensin converting enzyme (ACE), angiotensin receptor 1 (AT1R), and AT2R in synovial tissue of osteoarthritis (OA) at different stages. Methods: The patients who were treated with upper knee amputation because of trauma or total knee arthroplasty for OA between January 2018 and December 2018 were enrolled. Among them, 32 patients who met the selection criteria were included in the study. According to the Kellgren-Lawrence (K-L) X-ray classification, they were allocated to normal synovial group (group A, n=9), moderate OA synovial group (group B, n=11, K-L level 3), and advanced OA synovial group (group C, n=12, K-L level 4). The relative expressions of Renin, ACE, AT1R, and AT2R mRNAs and proteins were detected by real-time fluorescence quantitative PCR (qRT-PCR) and Western blot. Results: The relative expressions of Renin, ACE, and AT1R mRNAs and proteins were significantly higher in group B and group C than in group A ( P<0.05). The relative expressions of ACE and AT1R mRNAs and proteins and Renin protein were significantly higher in group C than in group B ( P<0.05). However, the relative expressions of AT2R mRNA and protein were lower in group B and group C than in group A ( P<0.05), and in group C than in group B ( P<0.05). Conclusion: The expressions of Renin, ACE, and AT1R in synovial tissue of osteoarthritis significantly increase as the K-L level increased, and the expression of AT2R decreases. Renin, ACE, AT1R, and AT2R have a certain degree of correlation with the development of OA.

4.
Eat Weight Disord ; 2020 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-32180210

RESUMO

OBJECTIVE: The aim of this study was to investigate how obesity was covered in Chinese newspapers from 1999 to 2018, demonstrating the trends and the characteristics of obesity-related news. METHODS: Content analysis was conducted to analyze a total of 358 news articles spanning two decades (1999-2018). We explored how Chinese newspapers portrayed obesity in terms of the evidence/sources cited in articles, its impacts, drivers/causes, and solutions; and how such portrayals have evolved over time. We further compared the articles across different types of newspapers (government-sponsored vs. commercial), two subpopulations (children vs. adults), and periods of time (1999-2008 vs. 2009-2018). RESULTS: Results showed that medical experts' interviews and statistics were the two most cited types of evidence in the articles. When discussing causes and solutions of obesity, factors pertaining to personal lifestyles were mentioned most frequently. Compared to psychological and social impacts, physical health risk was stressed more often. Compared with commercial newspapers, government-funded newspapers mentioned societal drivers of obesity and suggested reforming schools more frequently. Such differences were also found between coverage of child obesity and adult obesity. Our research, furthermore, revealed significant differences of media coverage of obesity across the two decades. CONCLUSIONS: Our findings indicate that obesity was generally depicted as a "self-regulated epidemic" in Chinese newspapers. Although the revealed causes and consequences of obesity are evidently related to individual factors, more attention should be directed to the roles that the government, media, and the society can play in preventing obesity and mitigating related social/economic burden. LEVEL OF EVIDENCE: Level V, cross-sectional descriptive study.

5.
Nature ; 579(7797): 51-55, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32132691

RESUMO

A wide range of metals exhibit anomalous electrical and thermodynamic properties when tuned to a quantum critical point (QCP), although the origins of such strange metals have posed a long-standing mystery. The frequent association of strange metals with unconventional superconductivity and antiferromagnetic QCPs1-4 has led to the belief that they are highly entangled quantum states5. By contrast, ferromagnets are regarded as an unlikely setting for strange metals, because they are weakly entangled and their QCPs are often interrupted by competing phases or first-order phase transitions6-8. Here we provide evidence that the pure ferromagnetic Kondo lattice9,10 CeRh6Ge4 becomes a strange metal at a pressure-induced QCP. Measurements of the specific heat and resistivity under pressure demonstrate that the ferromagnetic transition is continuously suppressed to zero temperature, revealing a strange-metal behaviour around the QCP. We argue that strong magnetic anisotropy has a key role in this process, injecting entanglement in the form of triplet resonating valence bonds into the ordered ferromagnet. We show that a singular transformation in the patterns of the entanglement between local moments and conduction electrons, from triplet resonating valence bonds to Kondo-entangled singlet pairs at the QCP, causes a jump in the Fermi surface volume-a key driver of strange-metallic behaviour. Our results open up a direction for research into ferromagnetic quantum criticality and establish an alternative setting for the strange-metal phenomenon. Most importantly, strange-metal behaviour at a ferromagnetic QCP suggests that quantum entanglement-not the destruction of antiferromagnetism-is the common driver of the varied behaviours of strange metals.

6.
J Fish Dis ; 43(4): 431-443, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32056240

RESUMO

The caspase family proteins are aspartate-specific cysteine proteases that transmit extracellular signals to cells, ultimately cause apoptosis and therefore play a key role in cellular immunity. In this study, we cloned and characterized three caspases from Chinese black sleeper (Bostrychus sinensis), Bscasp-1, Bscasp-8 and Bscasp-9. Real-time PCR analysis showed that Bscasp-1, Bscasp-8 and Bscasp-9 were universally expressed in all tested tissues of B. sinensis. Expression analyses showed that after poly(I:C) stimulation and bacterial (Vibrio parahaemolyticus) infection, the three caspases were significantly upregulated. After poly(I:C) stimulation, the change of Bscasp-1 expression in the head kidney was the most obvious; peak expression was about 80.78-fold more than that of the control. In addition, the expression of Bscasp-8 and Bscasp-9 in the peripheral blood and liver was 167.99- and 17.98-fold higher than that in the control group, respectively. After V. parahaemolyticus infection, the expression peaks of Bscasp-1 and Bscasp-8 in the peripheral blood and spleen were 85.82-fold and 280.83-fold that of the control. However, the expression of Bscasp-9 in the peripheral blood was upregulated only 8.33-fold higher than that in the control group. These results indicate that Bscasp-1, Bscasp-8 and Bscasp-9 are likely involved in response to viral and bacterial infection.

7.
Nanoscale ; 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-32068223

RESUMO

Fabricating lanthanide doped up-conversion luminescence based nanocomposites has drawn increasing attention in nanoscience and nanotechnology. Although challenging in precise synthesis, structure manipulation and interfacial engineering, fabricating dendritic mesoporous silica coated up-conversion nanoparticles (UCNP@dMSNs) with a tunable pore size is of great importance for the functionalization and application of UCNPs. Herein, we report a strategy to prepare uniform monodisperse UCNP@dMSNs with a core-shell structure. The silica shell has tunable center-radial and dendritic mesoporous channels. The synthesis was carried out in the heterogeneous oil-water microemulsion phase of the Winsor III system reaction system, which allows silica to be deposited directly on hydrophobic UCNPs through the self-anchoring of micelle complexes on the oleic acid ligand. The average pore size of UCNP@dMSNs could be tailored from ∼10 to ∼35 nm according to the varied amounts of co-solvent in the mixture. The microemulsion approach could also be used to prepare hierarchical UCNP@dMSNs with a multi-generational mesostructure. The resultant UCNP@dMSNs exhibit the unique advantage of loading "guest" nanoparticles in a self-absorption manner. We proved that Cu1.8S NPs (∼10 nm), Au NPs (∼10 nm) and Fe3O4 NPs (∼25 nm) could be incorporated in UCNP@dMSNs, which in turn validates the high adsorption capacity of UCNP@dMSNs.

8.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 34(2): 196-199, 2020 Feb 15.
Artigo em Chinês | MEDLINE | ID: mdl-32030951

RESUMO

Objective: To compare the cost changes of total knee arthroplasty (TKA) before and after the cancellation of medical consumables addition, so as to provide reference for the national medical reform policy. Methods: The patients treated with TKA between September 2018 and February 2019 were admitted as objects of study, and 372 of them met the selection criteria and were finally included in the study. According to the time node of cancelling the medical consumables addition (December 24, 2018), all patients were allocated to pre-cancelling and post-cancelling groups ( n=186). The clinical data of patients (gender, age, length of stay, disease classification), and various treatment costs (the costs of diagnosis and treatment, examination, laboratory, material, anesthesia, bed, nursing, operation, drug, and others) were collected. And the changes of various costs and proportions before and after cancelling the medical consumables addition were compared. Results: There was no significant difference in gender, age, and disease classification between the two groups ( P>0.05); the length of stay after cancelling the medical consumables addition was significantly longer than that before cancelling ( t=2.114, P=0.035). There was no significant difference in the total cost of TKA before and after cancelling the medical consumables addition ( t=0.214, P=0.831). Compared with that before cancelling the medical consumables addition, the cost of material was significantly reduced, and the costs of diagnosis and treatment, anesthesia, nursing, and operation were significantly increased ( P<0.05); the costs of examination, laboratory , bed, drug, and others were basically stable, and the differences were not significant ( P>0.05). Conclusion: The total cost of TKA is stable, the proportion of material cost is significantly reduced, the proportion of diagnosis and treatment cost reflecting the technical content of medical staff is significantly increased, which is in line with the expectation of the national policy of cancelling the medical consumables addition.


Assuntos
Artroplastia do Joelho , Hospitalização , Humanos , Tempo de Internação
9.
Cell Death Differ ; 2020 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-32094512

RESUMO

KIAA1429 (also known as vir-like m6A methyltransferase-associated protein (VIRMA)), a newly identified component of the RNA m6A methyltransferase complex, plays critical roles in guiding region-selective m6A deposition. However, in mammals, whether KIAA1429 mediates RNA m6A regulatory pathway functions in vivo remains unknown. Here, we show that the Kiaa1429-specific deficiency in oocytes resulted in female infertility with defective follicular development and fully grown germinal vesicle (GV) oocytes failing to undergo germinal vesicle breakdown (GVBD) and consequently losing the ability to resume meiosis. The oocyte growth is accompanied by the accumulation of abundant RNAs and posttranscriptional regulation. We found that the loss of Kiaa1429 could also lead to abnormal RNA metabolism in GV oocytes. RNA-seq profiling revealed that Kiaa1429 deletion altered the expression pattern of the oocyte-derived factors essential for follicular development. In addition, our data show that the conditional depletion of Kiaa1429 decreased the m6A levels in oocytes and mainly affected the alternative splicing of genes associated with oogenesis. In summary, the m6A methyltransferase KIAA1429-mediated RNA metabolism plays critical roles in folliculogenesis and the maintenance of oocyte competence.

10.
Science ; 367(6477): 580-586, 2020 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-31949099

RESUMO

N 6-methyladenosine (m6A) regulates stability and translation of messenger RNA (mRNA) in various biological processes. In this work, we show that knockout of the m6A writer Mettl3 or the nuclear reader Ythdc1 in mouse embryonic stem cells increases chromatin accessibility and activates transcription in an m6A-dependent manner. We found that METTL3 deposits m6A modifications on chromosome-associated regulatory RNAs (carRNAs), including promoter-associated RNAs, enhancer RNAs, and repeat RNAs. YTHDC1 facilitates the decay of a subset of these m6A-modified RNAs, especially elements of the long interspersed element-1 family, through the nuclear exosome targeting-mediated nuclear degradation. Reducing m6A methylation by METTL3 depletion or site-specific m6A demethylation of selected carRNAs elevates the levels of carRNAs and promotes open chromatin state and downstream transcription. Collectively, our results reveal that m6A on carRNAs can globally tune chromatin state and transcription.

11.
Cell Death Dis ; 11(1): 17, 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31907348

RESUMO

Endoplasmic reticulum (ER) stress-associated cell death is prevalent in various liver diseases. However, the determinant mechanism how hepatocytes survive unresolved stress was still unclear. Interleukin-24 (IL-24) was previously found to promote ER stress-mediated cell death, and yet its expression and function in the liver remained elusive. Here we identified an antiapoptotic role of IL-24, which transiently accumulated within ER-stressed hepatocytes in a X-box binding protein 1 (XBP1)-dependent manner. Disruption of IL-24 increased cell death in the CCL4- or APAP-challenged mouse liver or Tm-treated hepatocytes. In contrast, pharmaceutical blockade of eukaryotic initiation factor 2α (eIF2α) or genetical ablation of C/EBP homologous protein (CHOP) restored hepatocyte function in the absence of IL-24. In a clinical setting, patients with acute liver failure manifested a profound decrease of hepatic IL-24 expression, which was associated with disease progression. In conclusion, intrinsic hepatocyte IL-24 maintains ER homeostasis by restricting the eIF2α-CHOP pathway-mediated stress signal, which might be exploited as a bio-index for prognosis or therapeutic intervention in patients with liver injury.

12.
BMJ Open ; 10(1): e030501, 2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31924632

RESUMO

OBJECTIVES: To evaluate the morphine-sparing effects of the sequential treatment versus placebo in subjects undergoing total knee arthroplasty (TKA), the effects on pain relief, inflammation control and functional rehabilitation after TKA and safety. DESIGN: Double-blind, pragmatic, randomised, placebo-controlled trial. SETTING: Four tertiary hospitals in China. PARTICIPANTS: 246 consecutive patients who underwent elective unilateral TKA because of osteoarthritis (OA). INTERVENTIONS: Patients were randomised 1:1 to the parecoxib/celecoxib group or the control group. The patients in the parecoxib/celecoxib group were supplied sequential treatment with intravenous parecoxib 40 mg (every 12 hours) for the first 3 days after surgery, followed by oral celecoxib 200 mg (every 12 hours) for up to 6 weeks. The patients in the control group were supplied with the corresponding placebo under the same instructions. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary endpoint was the cumulative opioid consumption at 2 weeks post operation (intention-to-treat analysis). Secondary endpoints included the Knee Society Score, patient-reported outcomes and the cumulative opioid consumption. RESULTS: The cumulative opioid consumption at 2 weeks was significantly smaller in the parecoxib/celecoxib group than in the control group (median difference, 57.31 (95% CI 34.66 to 110.33)). The parecoxib/celecoxib group achieving superior Knee Society Scores and EQ-5D scores and greater Visual Analogue Scale score reduction during 6 weeks. Interleukin 6, erythrocyte sedation rate and C-reactive protein levels were reduced at 72 hours, 2 weeks and 4 weeks and prostaglandin E2 levels were reduced at 48 hours and 72 hours in the parecoxib/celecoxib group compared with the placebo group. The occurrence of adverse events (AEs) was significantly lower in the parecoxib/celecoxib group. CONCLUSIONS: The sequential intravenous parecoxib followed by oral celecoxib regimen reduces morphine consumption, achieves better pain control and functional recovery and leads to less AEs than placebo after TKA for OA. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov (ID: NCT02198924).

13.
Artigo em Inglês | MEDLINE | ID: mdl-31938892

RESUMO

PURPOSE: To assess the safety, biodistribution, and radiation dosimetry of the novel positron emission tomography (PET) radiopharmaceutical 1-((2-fluoro-6-[[18F]]fluorophenyl)sulfonyl)-4-((4-methoxyphenyl)sulfonyl)piperazine ([18F]DASA-23) in healthy volunteers. METHODS: We recruited 5 healthy volunteers who provided a written informed consent. Volunteers were injected with 295.0 ± 8.2 MBq of [18F]DASA-23 intravenously. Immediately following injection, a dynamic scan of the brain was acquired for 15 min. This was followed by serial whole-body PET/MRI scans acquired up to 3 h post-injection. Blood samples were collected at regular intervals, and vital signs monitored pre- and post-radiotracer administration. Regions of interest were drawn around multiple organs, time-activity curves were calculated, and organ uptake and dosimetry were estimated with OLINDA/EXM (version 1.1) software. RESULTS: All subjects tolerated the PET/MRI examination, without adverse reactions to [18F]DASA-23. [18F]DASA-23 passively crossed the blood-brain barrier, followed by rapid clearance from the brain. High accumulation of [18F]DASA-23 was noted in organs such as the gallbladder, liver, small intestine, and urinary bladder, suggesting hepatobiliary and urinary clearance. The effective dose of [18F]DASA-23 was 23.5 ± 5.8 µSv/MBq. CONCLUSION: We successfully completed a pilot first-in-human study of [18F]DASA-23. Our results indicate that [18F]DASA-23 can be used safely in humans to evaluate pyruvate kinase M2 levels. Ongoing studies are evaluating the ability of [18F]DASA-23 to visualize intracranial malignancies, NCT03539731. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03539731 (registered 28 May 2018).

14.
Int Orthop ; 44(3): 461-469, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31900576

RESUMO

BACKGROUND: The efficacy of partial retention of well-fixed components during two-stage exchange for chronic total hip arthroplasty (THA) infection has remained unknown. METHODS: A total of 14 patients with chronic infected THA were treated with damage control two-stage revision, including selective retention of the well-fixed femoral or acetabular component, aggressive debridement, antibiotic-laden cement spacer, antibiotic therapy, and delayed reimplantation. Indications for this treatment included chronic infected THAs with ingrown femoral or acetabular component and positive microbial growth with sensitive antibiotics. We excluded patients with acute infection; negative microbial growth; positive pathogen with high-virulence bacterial infections and multiple drug-resistant bacteria such as methicillin-resistant Staphylococcus aureus, fungi, and Mycobacterium tuberculosis; sinus formation; a prior failure for periprosthetic joint infection (PJI) treatment; and obvious bone resorption in both femoral and acetabulum side. During the study period, this represented 3.3% (14/425) of the patients treated for infected THA. Minimum follow-up was three  years. None of the 14 patients in this series were lost to follow-up. Successful treatment was defined according to a modified Delphi-based international multidisciplinary consensus. RESULTS: No repeated debridement and recurrence of infection occurred during the study period; no patient need chronic antibiotic suppression. Successful treatment of chronic PJI was achieved in all patients. Despite the high peri-operative complication rate, no severe consequences were observed. The mean Harris Hip Score was 86 (range, 82-92; SD, 3.3). CONCLUSIONS: The selective partial implant retention two-stage revision for chronic PJI may be a treatment option in properly selected patients with low virulence bugs.

15.
J Arthroplasty ; 35(2): 331-334, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31706646

RESUMO

BACKGROUND: Osteonecrosis of the femoral head (ONFH) is an increasing worldwide health problem. However, about 30% of the patients are diagnosed with idiopathic ONFH, which means no underlying etiology is identified. We hypothesized that acetabular anatomical abnormalities might be related to idiopathic ONFH. METHODS: This retrospective, 1:2 matched, case-control study included 101 patients (136 hips) with idiopathic ONFH and 202 control subjects (404 hips) matched for age, gender, and body mass index who had no apparent radiographic hip pathologies. The anteroposterior pelvic X-rays of the patients and control subjects were used to measure the anatomical parameters including the center-edge angle, the sharp angle, the acetabular depth ratio (ADR), and the acetabular head index (AHI). RESULTS: We found that hips with idiopathic osteonecrosis had less acetabular coverage, lower center-edge angle (28.3° vs 32.3°, P < .001), acetabular depth ratio (298.0 vs 306.4, P = .006), and acetabular head index (82.2 vs 85.8, P < .001), and higher sharp angle (39.7° vs 38.0°, P < .001), compared with the control subjects. The incidence of acetabular dysplasia was also higher in the idiopathic ONFH group than the control group. CONCLUSION: Less acetabular coverage was found in hips with idiopathic osteonecrosis than the control subjects. Less acetabular coverage may be associated with the development of ONFH in East Asian population.

16.
Fish Shellfish Immunol ; 96: 41-52, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31794842

RESUMO

In this study, we sequenced and characterized the goose-type lysozyme gene, termed as BsLysG, from the Chinese black sleeper (Bostrychus sinensis). The BsLysG encodes 196 amino acids and contains a soluble bacterial lytic transglycosylases domain, three catalytic residues (Glu72, Asp85 and Asp102) and the GLMQ motif (Gly97, Leu98, Met99 and Gln100). No signal peptide was observed in the BsLysG protein. The genomic DNA of BsLysG contains five exons and four introns. The sequence analyses showed that the BsLysG exhibits high similarity with LysG from other fishes. Phylogenetic analyses showed that the BsLysG is clustered together with its counterparts from other teleost fishes. The Real-time PCR analyses showed that the BsLysG was found to be ubiquitously expressed in ten examined organs in Chinese black sleeper, with predominant expression in spleen, followed by head kidney and peripheral blood. Expression analyses showed that the BsLysG was significantly upregulated in vivo after either pathogen Vibrio parahemolyticus infection or poly (I:C) challenge in peripheral blood, head kidney, liver and spleen organs. The purified recombinant BsLysG (rBsLysG) has optimal activity at 35 °C and pH 5.5. The rBsLysG exhibited antimicrobial activity against two Gram-positive bacteria (Micrococcus lysodeikticus and Staphylococcus aureus) and two Gram-negative bacteria (Escherichia coli and V. parahemolyticus). The Scanning electron microscope (SEM) imaging analyses showed that the rBsLysG-treated V. parahemolyticus cells displayed morphological deformation. These results indicate that the BsLysG is involved in host immune defense against bacterial infection.

17.
Am J Med Sci ; 359(1): 17-26, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31785770

RESUMO

BACKGROUND: The purpose of this study was to demonstrate the role of renin-angiotensin system (RAS)-related components, vascular endothelial growth factor (VEGF) and atrial metalloproteinase-13 (MMP-13) in synovial tissue and synovial fluid from patients with rheumatoid arthritis (RA) and osteoarthritis (OA). MATERIALS AND METHODS: Thirty-four patients with RA and 41 patients with OA were included in the study. Renin, angiotensin-converting enzyme (ACE), VEGF and MMP-13 protein levels in the synovial fluid were measured by enzyme-linked immunosorbent assay. Quantitative real-time polymerase chain reaction analysis, western blot analysis and immunohistochemistry were used to quantify renin, ACE, angiotensin type 1 and type 2 receptors, VEGF and MMP-13 in OA and RA. Additionally, the correlation was determined by Pearson's coefficient. RESULTS: In synovial fluid, expression levels of renin, ACE, VEGF and MMP-13 in patients with RA were significantly higher than those in patients with OA. In synovial tissue, the RAS components VEGF and MMP-13 were also elevated in patients with RA. The results of immunohistochemistry in synovial tissue also showed that the RAS components VEGF and MMP-13 were significantly increased in patients with RA. Notably, the Pearson coefficient demonstrated that the levels of the RAS components were positively correlated with the expression of VEGF and MMP-13 in OA and RA. CONCLUSIONS: The present results suggest that RAS-related components in RA and OA, including renin, ACE, angiotensin type 1 and type 2 receptors, are associated with increased expression of VEGF and play an important role in angiogenesis. Furthermore, there was a significant positive correlation between the expression of VEGF and MMP-13.

18.
Br J Cancer ; 122(5): 640-647, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31853007

RESUMO

BACKGROUND: We have been investigating the molecular mechanisms of cisplatin-induced chemoresistance in head and neck squamous cell carcinoma (HNSCC). Based on our previous findings, the present study investigates how the Mre11, Rad50, and NBS1 (MRN) DNA repair complex interacts at the molecular level with the programmed cell death ligand 1 (PD-L1) in cisplatin-induced chemoresistance. METHODS: Human HNSCC cell lines were used to determine the role played by PD-L1 in cisplatin resistance. Initial experiments investigated PD-L1 expression levels in cells exposed to cisplatin and whether PD-L1 interacts directly with the MRN complex. Finally, in vitro studies and in vivo experiments on BALB/c nu/nu mice were performed to determine whether interference of PD-L1 or NBS1 synthesis modulated cisplatin resistance. RESULTS: Exposure to cisplatin resulted in PD-L1 being upregulated in the chemoresistant but not the chemosensitive cell line. Subsequent co-immunoprecipitation studies demonstrated that PD-L1 associates with NBS1. In addition, we found that the knockdown of either PD-L1 or NBS1 re-sensitised the chemoresistant cell line to cisplatin. Finally, but perhaps most importantly, synergy was observed when both PD-L1 and NBS1 were knocked down making the formerly chemoresistant strain highly cisplatin sensitive. CONCLUSIONS: PD-L1 plays a pivotal role in cisplatin resistance in chemoresistant human HNSCC cell lines.

19.
J Magn Reson Imaging ; 51(1): 183-194, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31044459

RESUMO

BACKGROUND: H2 15 O-positron emission tomography (PET) is considered the reference standard for absolute cerebral blood flow (CBF). However, this technique requires an arterial input function measured through continuous sampling of arterial blood, which is invasive and has limitations with tracer delay and dispersion. PURPOSE: To demonstrate a new noninvasive method to quantify absolute CBF with a PET/MRI hybrid scanner. This blood-free approach, called PC-PET, takes the spatial CBF distribution from a static H2 15 O-PET scan, and scales it to the whole-brain average CBF value measured by simultaneous phase-contrast MRI. STUDY TYPE: Observational. SUBJECTS: Twelve healthy controls (HC) and 13 patients with Moyamoya disease (MM) as a model of chronic ischemic disease. FIELD STRENGTH/SEQUENCES: 3T/2D cardiac-gated phase-contrast MRI and H2 15 O-PET. ASSESSMENT: PC-PET CBF values from whole brain (WB), gray matter (GM), and white matter (WM) in HCs were compared with literature values since 2000. CBF and cerebrovascular reactivity (CVR), which is defined as the percent CBF change between baseline and post-acetazolamide (vasodilator) scans, were measured by PC-PET in MM patients and HCs within cortical regions corresponding to major vascular territories. Statistical Tests: Linear, mixed effects models were created to compare CBF and CVR, respectively, between patients and controls, and between different degrees of stenosis. RESULTS: The mean CBF values in WB, GM, and WM in HC were 42 ± 7 ml/100 g/min, 50 ± 7 ml/100 g/min, and 23 ± 3 ml/100 g/min, respectively, which agree well with literature values. Compared with normal regions (57 ± 23%), patients showed significantly decreased CVR in areas with mild/moderate stenosis (47 ± 17%, P = 0.011) and in severe/occluded areas (40 ± 16%, P = 0.016). Data Conclusion: PC-PET identifies differences in cerebrovascular reactivity between healthy controls and cerebrovascular patients. PC-PET is suitable for CBF measurement when arterial blood sampling is not accessible, and warrants comparison to fully quantitative H2 15 O-PET in future studies. LEVEL OF EVIDENCE: 3 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2019. J. Magn. Reson. Imaging 2020;51:183-194.

20.
Mol Ther Nucleic Acids ; 19: 15-30, 2019 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-31790972

RESUMO

Osteoarthritis (OA) is a major cause of joint pain and disability, and chondrocyte senescence is a key pathological process in OA and may be a target of new therapeutics. MicroRNA-140 (miR-140) plays a protective role in OA, but little is known about its epigenetic effect on chondrocyte senescence. In this study, we first validated the features of chondrocyte senescence characterized by increased cell cycle arrest in the G0/G1 phase and the expression of senescence-associated ß-galactosidase (SA-ßGal), p16INK4a, p21, p53, and γH2AX in human knee OA. Then, we revealed in interleukin 1ß (IL-1ß)-induced OA chondrocytes in vitro that pretransfection with miR-140 effectively inhibited the expression of SA-ßGal, p16INK4a, p21, p53, and γH2AX. Furthermore, in vivo results from trauma-induced early-stage OA rats showed that intra-articularly injected miR-140 could rapidly reach the chondrocyte cytoplasm and induce molecular changes similar to the in vitro results, resulting in a noticeable alleviation of OA progression. Finally, bioinformatics analysis predicted the potential targets of miR-140 and a mechanistic network by which miR-140 regulates chondrocyte senescence. Collectively, miR-140 can effectively attenuate the progression of early-stage OA by retarding chondrocyte senescence, contributing new evidence of the involvement of miR-mediated epigenetic regulation of chondrocyte senescence in OA pathogenesis.

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