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1.
Biosci Rep ; 40(4)2020 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-32297643

RESUMO

The Gremlin-2 (GREM2) plays crucial roles in modulating bone homeostasis through the bone morphogenetic protein-2 pathway. However, GREM2 gene variants in osteoporosis were less frequent in a Chinese population. Therefore, the present study recruited 310 patients with osteoporosis and 339 healthy postmenopausal women to assess the correlation of GREM2 gene polymorphisms with the risk of osteoporosis. Polymerase chain reaction (PCR) and Sanger sequencing were utilized to genotype samples. The results showed that GREM2 gene rs4454537, not rs11588607, polymorphism was significantly associated with an increased risk of osteoporosis in postmenopausal women. Moreover, stratified analyses indicated a significant association between rs4454537 polymorphisms and body mass index of <25 kg/m2. Additionally, the association between GREM2 rs4454537 polymorphism and clinical characteristics was assessed, which showed that this locus decreased the bone mineral density (BMD) in postmenopausal osteoporotic individuals. Furthermore, individuals with CC genotype appeared to have a higher GREM2 expression compared with those bearing the TT genotype of rs4454537 polymorphism. However, the genotype distribution of rs4454537 polymorphism showed no statistical difference between osteoporotic patients as a function of fracture status. In summary, GREM2 rs4454537 polymorphism decreases BMD and increases osteoporotic risk in postmenopausal women.

2.
Zhongguo Gu Shang ; 33(2): 126-30, 2020 Feb 25.
Artigo em Chinês | MEDLINE | ID: mdl-32133810

RESUMO

OBJECTIVE: To investigate the influence of posterior osteotomy on spinopelvic parameters in lumbar degenerative kyphosis (LDK) patients. METHODS: The clinical data of 21 patients with lumbar degenerative kyphosis who underwent osteotomy from January 2012 to December 2015 were retrospectively analyzed. There were 5 males and 16 females, aged from 55 to 76 years with an average of (66.24±5.13) years. All patients had taken preoperative and postoperative full length spinal X-ray, analyzing the spinopelvic parameters as thoracic kyphosis (TK), lumbar lordosis (LL), sagittal vertical axis (SVA), pelvic incidence (PI), pelvic tilt (PT) and sacral slope (SS). RESULTS: All operations were successful, the average operative time was 190 min (160 to 220 min) and intraoperative blood loss was 1 000 ml (800 to 1900 ml). Parameters of the patients between preoperative and period 1-year follow-up were as follows : preoperative TK increased from (31.67±21.13) ° to (34.67±11.60) °, LL corrected from (4.76±3.17) ° to (37.41±6.28) °, PT reduced from (33.94±5.01) ° to (20.12±5.36) °, and SS improved from (18.47±2.60) ° to (31.71±4.30) °, SVA restored from (13.24±3.60) cm to (2.82±1.33) cm. There were significant differences of spinopelvic parameters between preoperation and postoperation (P<0.05). CONCLUSION: Posterior osteotomy can effectively reconstruct the sagittal balance of spinopelvis in patients with lumbar degenerative kyphosis. The recovery of lumbar lordosis and sacral slope is closely related to the reconstruction of sagittal balance.


Assuntos
Cifose , Lordose , Escoliose , Idoso , Feminino , Humanos , Vértebras Lombares , Masculino , Pessoa de Meia-Idade , Osteotomia , Estudos Retrospectivos
3.
Life Sci ; 252: 117589, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32220622

RESUMO

BACKGROUND: Renal fibrosis is the characteristic of all kinds of chronic kidney diseases (CKDs). Fascin-1 plays an important role in tumor development, but the roles of fascin-1 in renal fibrosis have not been studied. Here, we explored the role of fascin-1 in renal fibrosis and the potential mechanisms. METHODS: Kidney unilateral ureteral obstruction (UUO) mouse model was used as an in vivo model, and proximal tubule epithelial cell lines treated with TGF-ß1 were used as in vitro model of renal fibrosis. Cell transfection was performed to manipulate the expression of miR-200b/c, fascin-1 and CD44. Western blotting, qRT-PCR, immunohistochemistry or immunofluorescence assays were used to measure levels of miR-200b/c, fascin-1, CD44, and fibrosis and EMT-related markers. H&E and Masson stainings were used to examine the degree of injury and fibrosis in kidneys. Dual luciferase assay was used to examine the interaction between miR-200b/c family and fascin-1. RESULTS: Fascin-1 and CD44 levels were both significantly up-regulated while miR-200b/c family was reduced in models of renal fibrosis. Furthermore, overexpression of miR-200b/c family and inhibition of fascin-1 or CD44 ameliorated renal fibrosis through suppressing EMT process. Mechanistically, miR-200b/c family directly and negatively regulated the expression of fascin-1. Overexpression of fascin-1 could reverse the effects of miR-200b/c family on renal fibrosis, and fascin-1 regulated renal fibrosis by activating CD44. CONCLUSION: Our study is the first to show that fascin-1 plays a critical role in renal fibrosis. MiR-200b/c family could inhibit renal fibrosis through modulating EMT process by directly targeting fascin-1/CD44 axis.

4.
Virol J ; 17(1): 33, 2020 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-32156292

RESUMO

BACKGROUND: Chilli veinal mottle virus (ChiVMV), which belongs to the genus Potyvirus of the family Potyviridae, mainly infects solanaceous plants and has caused serious economic losses in Asia and Africa. Tobacco plants infected with ChiVMV suffered from punctate necrosis of leaves, leaf deformation, systemic necrosis of leaves and stems, and eventually plant death. However, ChiVMV infection could not usually be identified given the lack of rapid and efficient detection assays in tobacco plants. Therefore, an isolate of tobacco-infecting ChiVMV (ChiVMV-LZ) was obtained, and a novel isothermal amplification and detection technique, reverse transcription-recombinase polymerase amplification (RT-RPA), was established to detect ChiVMV in tobacco plants. METHODS: In this study, the full-length genome of ChiVMV-LZ was obtained using reverse transcription-polymerase chain reaction (RT-PCR) and rapid amplification of cDNA ends (RACE) assays. The genome sequence of ChiVMV-LZ was characterized by sequence alignment and phylogenetic analysis. Then, a RT-RPA assay was established for rapid and sensitive detection of ChiVMV-LZ in tobacco. Additionally, the established RT-RPA assay was compared to the RT-PCR assay in aspect of sensitivity and application in field-collected tobacco samples. RESULTS: ChiVMV-LZ was isolated from diseased tobacco in Luzhou, Sichuan, China. The tobacco plants inoculated with ChiVMV-LZ showed typical symptoms of yellow and round spots on the leaves, and curled and folded leaf margin, similar to those observed on naturally ChiVMV-infected tobacco in the field. The full-length genomic sequence of ChiVMV-LZ was determined to be 9742 nucleotides. Sequence alignment and phylogenetic analysis showed that ChiVMV-LZ was most closely related to ChiVMV-Yp8 isolated from pepper plants in Sichuan province while distantly related to ChiVMV-YN from tobacco in Yunnan province, indicating a possibly geographical differentiation of ChiVMV isolates. Additionally, a RT-RPA assay was established for rapid detection of ChiVMV in tobacco. The RT-RPA has no cross-reaction with other related tobacco viruses and is about 10-fold more sensitive than conventional RT-PCR method. CONCLUSION: The characterization of ChiVMV-LZ infecting tobacco was determined, and the established RT-RPA assay provides a reliable and effective method for rapid detection of ChiVMV in tobacco.

5.
Nat Commun ; 11(1): 680, 2020 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-32015344

RESUMO

Powdery mildew, caused by Blumeria graminis f. sp. tritici (Bgt), is one of the most destructive diseases that pose a great threat to wheat production. Wheat landraces represent a rich source of powdery mildew resistance. Here, we report the map-based cloning of powdery mildew resistance gene Pm24 from Chinese wheat landrace Hulutou. It encodes a tandem kinase protein (TKP) with putative kinase-pseudokinase domains, designated WHEAT TANDEM KINASE 3 (WTK3). The resistance function of Pm24 was validated by transgenic assay, independent mutants, and allelic association analyses. Haplotype analysis revealed that a rare 6-bp natural deletion of lysine-glycine codons, endemic to wheat landraces of Shaanxi Province, China, in the kinase I domain (Kin I) of WTK3 is critical for the resistance function. Transgenic assay of WTK3 chimeric variants revealed that only the specific two amino acid deletion, rather than any of the single or more amino acid deletions, in the Kin I of WTK3 is responsible for gaining the resistance function of WTK3 against the Bgt fungus.


Assuntos
Resistência à Doença/genética , Mutação com Ganho de Função , Genes de Plantas/genética , Doenças das Plantas/microbiologia , Triticum/genética , Ascomicetos/patogenicidade , China , Peróxido de Hidrogênio/metabolismo , Mutagênese , Imunidade Vegetal/genética , Proteínas de Plantas/genética , Plantas Geneticamente Modificadas , Domínios Proteicos , Proteínas Quinases/genética , Transformação Genética
6.
Eur J Cancer ; 128: 27-37, 2020 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-32109848

RESUMO

AIM: Tumour-associated macrophages (TAMs) are prominent immune cells infiltrating in solid tumours with phenotypic and functional heterogeneity. However, the clinical significance of heterogeneous subtypes of TAMs in gastric cancer still remains obscure. Here, we aimed to explore the clinical significance of TAMs expressing dendritic cell-specific intercellular adhesion molecule 3-grabbing non-integrin (DC-SIGN) and its relevance with immune contexture in gastric cancer. METHODS: We selected 453 formalin-fixed and paraffin-embedded samples and 51 fresh tissue specimens of patients with gastric cancer from Zhongshan Hospital. The association of DC-SIGN+ macrophages with clinicopathological parameters, overall survival (OS) and responsiveness to fluorouracil-based adjuvant chemotherapy (ACT) was inspected. Immunohistochemistry (IHC) and flow cytometry (FCM) were applied to characterize immune cells in gastric cancer. RESULTS: We demonstrated that high intratumoral DC-SIGN+ macrophages infiltration predicted poor OS and inferior therapeutic responsiveness to fluorouracil-based ACT in patients with gastric cancer. Furthermore, higher infiltration of DC-SIGN+ macrophages indicated an increased number of Foxp3+ regulatory T cells (Tregs), CD8+ T cells and a higher ratio of Foxp3+/CD8+ within the tumour microenvironment (TME). In addition, CD8+ T cells in DC-SIGN+ macrophages high subgroup were functionally impaired, showing decreased interferon-γ (IFN-γ), granzyme B (GZMB) and perforin production yet elevated programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) expression. CONCLUSIONS: DC-SIGN+ macrophages were associated with immunoinvasive TME and indicated poor prognosis and inferior therapeutic responsiveness to fluorouracil-based ACT. DC-SIGN+ macrophages might be an independent prognosticator and a potential immunotherapeutic target for gastric cancer.

7.
Cancer Biomark ; 27(2): 265-275, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31929144

RESUMO

BACKGROUND: Tumor-infiltrating immune cells are indispensable to the progression and prognosis of clear cell renal cell carcinoma (ccRCC). OBJECTIVE: The aim of this study was to explore the clinical implications of immune cell infiltrates in ccRCC. METHODS: The Cancer Genome Atlas (TCGA) database (N= 515) and E-MTAB-1980 cohort of patients (N= 101) were adopted to estimate the prognostic value of immune cell infiltration. Twenty-four types of immune cells were evaluated using single-sample gene set enrichment analysis. Cox regression analyses were conducted to develop an immune risk score. RESULTS: Survival analyses revealed that 13 genes significantly associated with the overall survival (OS). Furthermore, multivariate Cox analysis identified an immune risk score on the basis of mast cells, natural killer CD56bright cells, T helper 17 (Th17) cells, and Th2 cells. The immune risk score was associated with OS, with hazard ratios of 2.72 (95% CI 2.17-3.40) and 3.24 (95% CI 1.64-6.44) in TCGA and E-MTAB-1980 datasets, respectively. This immune risk score was significantly correlated with some immunotherapy-related biomarkers. CONCLUSIONS: We profiled a prognostic signature and established an immune risk score model for ccRCC, which could provide novel predictive markers for patients with ccRCC and an indicator for immunotherapy response measurement.

8.
ACS Appl Mater Interfaces ; 12(6): 6840-6851, 2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-31999085

RESUMO

Recombinant human bone morphogenetic protein-2 (rhBMP-2) and bioceramic are the widely used bioactive factors in treatment of bone defects, but these easily cause side effects because of uncontrollable local concentration. In this study, rhBMP-2 was grafted on the surface of mesoporous bioglass nanoparticles (MBGNs) with an amide bond and then photo-cross-linked together with methacrylate gelatin (GelMA); in this way, a GelMA/MBGNs-rhBMP-2 hydrogel membrane was fabricated to release rhBMP-2 in a controllable program during the early bone regeneration period and then release calcium and silicon ions to keep promoting osteogenesis instead of rhBMP-2 in a long term. In this way, rhBMP-2 can keep releasing for 4 weeks and then the ions keep releasing after 4 weeks; this process is matched to early and late osteogenesis procedures. In vitro study demonstrated that the early release of rhBMP-2 can effectively promote local cell osteogenic differentiation in a short period, and then, the inorganic ions can promote cell adhesion not only in the early stage but also keep promoting osteogenic differentiation for a long period. Finally, the GelMA/MBGNs-rhBMP-2 hydrogel shows a superior capacity in long-term osteogenesis and promoting bone tissue regeneration in rat calvarial critical size defect. This GelMA/MBGNs-rhBMP-2 hydrogel demonstrated a promising strategy for the controllable and safer use of bioactive factors such as rhBMP-2 in artificial periosteum to accelerate bone repairing.

9.
J Clin Pharm Ther ; 45(3): 419-429, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31954070

RESUMO

WHAT IS KNOWN AND OBJECTIVE: Corticosteroids are recommended by almost all international guidelines for the management of exacerbations of chronic obstructive pulmonary disease (COPD). Nevertheless, due to their side effects, there are still concerns regarding the use of systemic corticosteroids (SCs). The Global Initiative for Chronic Obstructive Lung Disease guideline states nebulized budesonide (NB) may be a suitable alternative to SCs for treating COPD exacerbations. We conducted this study to systematically compare the efficacies of NB and SCs by using a meta-analysis. METHODS: PubMed, EMBASE and Cochrane Library databases were searched from database inception to 10 October 2019. Our main end points were change in pulmonary function and blood gas analysis. Secondary end points were numbers of exacerbations and hyperglycaemia. RESULTS AND DISCUSSION: Of 645 identified studies, 6 were eligible and were included in our analysis (N = 867 participants). Compared with SCs, NB was non-inferior on the change in FEV1 %predicted at 24 hours, 48-72 hours and 5-7 days; FEV1 at 5-7 days; FEV1 /FVC at 7 days. For blood gas analysis, our meta-analysis indicated that PaO2 , PaCO2 at 24 hours, 48-72 hours and 7-10 days and SaO2 at 24 hours and 7-10 days showed a non-significant difference in both groups, whereas the SaO2 was significant higher in NB group at 48-72 hours after treatment. Hyperglycaemia was less frequent with NB (odds ratio, 0.1; 95% CI, 0.01-0.85; P = .04). WHAT IS NEW AND CONCLUSION: Based on our meta-analysis, NB was not inferior to SCs when used in the treatment of COPD exacerbations. However, additional well-designed prospective studies are needed to identify the optimal dose of nebulized budesonide and the effects of nebulized budesonide in outpatients, or patients in ICU settings.

10.
Funct Integr Genomics ; 20(1): 1-16, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31250230

RESUMO

Although the economic value of wheat flour is determined by the complement of gluten proteins, these proteins have been challenging to study because of the complexity of the major protein groups and the tremendous sequence diversity among wheat cultivars. The completion of a high-quality wheat genome sequence from the reference wheat Chinese Spring recently facilitated the assembly and annotation of a complete set of gluten protein genes from a single cultivar, making it possible to link individual proteins in the flour to specific gene sequences. In a proteomic analysis of total wheat flour protein from Chinese Spring using quantitative two-dimensional gel electrophoresis combined with tandem mass spectrometry, gliadins or low-molecular-weight glutenin subunits were identified as the predominant proteins in 72 protein spots. Individual spots were associated with 40 of 56 Chinese Spring gene sequences, including 16 of 26 alpha gliadins, 10 of 11 gamma gliadins, six of seven omega gliadins, one of two delta gliadins, and nine of ten LMW-GS. Most genes that were not associated with protein spots were either expressed at low levels in endosperm or encoded proteins with high similarity to other proteins. A wide range of protein accumulation levels were observed and discrepancies between transcript levels and protein levels were noted. This work together with similar studies using other commercial cultivars should provide new insight into the molecular basis of wheat flour quality and allergenic potential.

11.
Diabetes ; 69(1): 121-126, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31658956

RESUMO

It is estimated that ∼1% of European ancestry patients clinically diagnosed with type 1 diabetes (T1D) actually have monogenic forms of the disease. Because of the much lower incidence of true T1D in East Asians, we hypothesized that the percentage would be much higher. To test this, we sequenced the exome of 82 Chinese Han patients clinically diagnosed with T1D but negative for three autoantibodies. Analysis focused on established or proposed monogenic diabetes genes. We found credible mutations in 18 of the 82 autoantibody-negative patients (22%). All mutations had consensus pathogenicity support by five algorithms. As in Europeans, the most common gene was HNF1A (MODY3), in 6 of 18 cases. Surprisingly, almost as frequent were diallelic mutations in WFS1, known to cause Wolfram syndrome but also described in nonsyndromic cases. Fasting C-peptide varied widely and was not predictive. Given the 27.4% autoantibody negativity in Chinese and 22% mutation rate, we estimate that ∼6% of Chinese with a clinical T1D diagnosis have monogenic diabetes. Our findings support universal sequencing of autoantibody-negative cases as standard of care in East Asian patients with a clinical T1D diagnosis. Nonsyndromic diabetes with WSF1 mutations is not rare in Chinese. Its response to alternative treatments should be investigated.

12.
Nephron ; 144(2): 96-108, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31661702

RESUMO

BACKGROUND: Chloroquine (CQ), a classic autophagy inhibitor, is used clinically for malaria prophylaxis and pulmonary hypertension treatment. The adverse effects of CQ on morphological and functional changes in the kidney were investigated in the current study due to CQ accumulation in the kidney. METHODS: Twelve male Sprague-Dawley rats were randomly divided into 2 groups for 4 weeks: group 1, control (n = 6); and group 2, CQ administration group (50 mg-1·kg per day ip; n = 6). Serum aldosterone and vasopressin were measured by radioimmunoassay. Immunofluorescence was used to colocalize Tunel with aquaporin 1, aquaporin 2 (AQP2), and Tamm-Horsfall protein. Expression of AQP2 and mineralocorticoid (MR) was detected by western blot and immunohistochemistry. RESULTS: In the present study, 4 weeks of CQ administration were shown to induce severe kidney injury, including glomerular sclerosis and tubular cells apoptosis, especially distal tubular cells. Decreased expression of LC3II/I and p-AKT was demonstrated in CQ-treated rats. Glomerular and proximal tubule injury were associated with impaired autophagy flux, and distal tubule injury may be associated with downregulated cyclic adenosine monophosphate (cAMP)/PKA/AKT signaling. Both MR and AQP2, which are mainly located in the distal tubule and collecting duct, were significantly reduced in CQ-treated rats, thus leading to increased exosomal secretion of AQP2 in urine. Additionally, chronic CQ administration increased aldosterone and vasopressin levels in serum, but lowered the blood pressure, glomerular filtration rate, and urine concentration. CONCLUSIONS: CQ administration damages glomerular, proximal tubule autophagy, and severe distal tubular cells apoptosis by inhibiting cAMP/PKA/AKT signaling.

13.
J Cell Physiol ; 235(3): 2220-2231, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31489629

RESUMO

Osteonectin binds strongly to type I collagen and hydroxyapatite and plays a crucial role in extracellular matrix mineralization. Previous studies have also shown that p38 signaling pathway is an important regulator for osteoblast mineralization. This study focused on the role of osteonectin in regulating extracellular matrix mineralization via the p38 signaling pathway. Osteoblasts were isolated and cultured from parietal bones of neonatal Sprague-Dawley rats. The gene and protein expressions of noncollagen proteins (BSP, bone sialoprotein; OCN, osteocalcin; OPN, osteopontin), p38 mitogen-activated protein kinase, and SIBLINGs (Small Integrin-Binding LIgand N-linked Glycoproteins) members (DMP1, dentine matrix protein 1, DSPP, dentin sialophosphoprotein, and MEPE, matrix extracellular phosphoglycoprotein) were detected by reverse-transcription quantitative polymerase chain reaction and western blot analysis. Alizarin red staining, intracellular calcium assay, and transmission electron microscopy were used to detect mineralization. Initially, by adding osteonectin at different concentrations in osteoblasts and detecting the above mineralization indexes, 1 µg/ml was determined to be the optima osteonectin concentration, which significantly increased gene expressions of BSP, OPN, OCN, DMP1, MEPE, DSPP, and p38 in osteoblasts, p38 and p-p38 protein expressions were also significantly increased, mineralized nodules were significantly enhanced; when added with SB203580 (a specific inhibitor for p38) these effects were inhibited. Furthermore, osteoblasts transfected with Ad-p38 also significantly upregulated the protein and gene expressions of noncollagens and SIBLINGs members, whereas transfection of p38-rhRNA showed the opposite effect. Our data suggest that osteonectin regulates the extracellular matrix mineralization of osteoblasts through the P38 signaling pathway.

14.
Biomaterials ; 227: 119555, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31655445

RESUMO

The periosteum plays a vital role in both development and injury healing process of bone. However, few researches have focused on artificial periosteum, which was also limited by the complexity on its construction and biological risks for clinical practice. In order to tackle this issue, inspired by the structural development of periosteum, we put forward a hierarchical micro/nanofibrous bionic periosteum with sustained releasing of VEGF as exogenous vascularized fibrous layer of periosteum to induce endogenous cambium layer in vivo for complete regeneration of periosteal and bone tissue, through collagen self-assembly and micro-sol electrospinning technologies. The VEGF encapsulated in hyaluronan-PLLA core-shell structure was demonstrated to be released in a durable way for angiogenesis in fibrous layer and bone defect area. Meanwhile, the self-assembly of collagen together with electrospun fibers contributed to a hierarchical micro/nanostructure which greatly mimicked the microenvironment of extracellular matrix to provide structural and biochemical cues for cell adhesion, proliferation and differentiation, and lead to the formation of cambium layer which mimicked the in-situ ossification manner as intramembranous ossification. As the motif of this study, the periosteal regeneration was characterized both by osteoblasts and periostin, which represented structural and molecular mechanisms respectively. Furthermore, the periosteal biomaterial proposed here possessed the superior abilities of scar inhibition, angiogenesis, osteogenesis to repair the bone defect in a uniform and rapid manner by inherent periosteal ossific mechanism involved in both intramembranous and endochondral ossification. Thus, the endogenous-exogenous combined bionic periosteum proved to be efficient and versatile in triggering periosteal and bone regeneration and hopefully supply a promising strategy for solving clinical issue.

15.
Mult Scler Relat Disord ; 39: 101888, 2019 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-31869599

RESUMO

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) and MS are the most common autoimmune inflammatory demyelinating diseases of the CNS. However, the mechanisms of pathogenesis are still unclear. nucleotide-binding leucine-rich repeat (NLR) family pyrin domain containing 3 (NLRP3), an important protein of the innate immune system that is activated by mitochondrial DNA (mtDNA), has been reported to be associated with various autoimmune disorders. OBJECTIVE: To assess the levels of cerebrospinal fluid (CSF) NLRP3, mtDNA and inflammation-associated cytokines (IL-1ß, IL-6 and IL-17) in patients with NMOSD and MS, and to examine the correlations between these factors. METHODS: 28 NMOSD patients, 15 MS patients, and 16 controls with non-inflammatory neurological diseases were recruited. NLRP3 inflammasome, IL-1ß, IL-6 and IL-17 were measured by ELISA. CSF extracellular mtDNA was measured by qPCR. The severity of clinical presentation was evaluated by EDSS score. RESULTS: CSF levels of NLRP3, mtDNA, IL-1ß, IL-6 and IL-17 were higher in NMOSD patients than in controls. Elevated CSF NLRP3, mtDNA and IL-6 were found in MS patients compared with controls. CSF NLRP3 and IL-6 levels were significantly higher in NMOSD patients than in MS patients. The EDSS scores of NMOSD patients during relapse were positively correlated with CSF NLRP3 and mtDNA. CONCLUSION: Our findings suggest that CSF levels of the NLRP3 inflammasome may serve as a diagnostic biomarker for distinguishing NMOSD and MS. Pyroptosis mediated by the NLRP3 inflammasome following mitochondrial damage may play an important role in the pathogenesis of these neuroinflammatory disorders, especially NMOSD.

16.
J Vasc Surg ; 2019 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-31882308

RESUMO

OBJECTIVE: Relatively little is known about the natural history of atherosclerotic common carotid artery occlusion and optimal treatment of these patients is still unclear. The aim of this retrospective study was to evaluate the immediate- and long-term outcomes of axillary to carotid bypass with polytetrafluoroethylene graft for symptomatic patients with chronic common carotid artery occlusion. METHODS: From March 2001 to December 2017, 58 symptomatic patients (41 men; mean age 64.7 years) with chronic common carotid artery occlusion underwent axillary to carotid bypass at one academic hospital. The clinical data of this patient cohort were retrospectively analyzed. The cumulative graft patency, overall survival, freedom from symptoms, and freedom from ipsilateral stroke were calculated with Kaplan-Meier method. RESULTS: Thirty-three patients presented with transient ischemic attack and 25 patients presented with minor stroke. At 30 days after bypass, the overall perioperative complication rate was 3.4% (2/58). Mild injuries of brachial plexus occurred in one (1.7%) patient and myocardial infarction occurred in one (1.7%) patient. No perioperative stroke or death occurred. The median follow-up was 51 months (range, 12-203) for this series. The cumulative graft patency rates at 1, 3, 5, and 10 years were 100%, 100%, 94%, and 83%, respectively. The cumulative freedom from symptoms rates at 1, 3, 5, and 10 years were 100%, 100%, 94%, and 75%, respectively. The cumulative freedom from ipsilateral stroke rates at 1, 3, 5, and 10 years were 100%, 100%, 94%, and 82%, respectively. The overall survival rates at 1, 3, 5, and 10 years were 98%, 89%, 81%, and 67%, respectively. CONCLUSIONS: Axillary to carotid bypass with polytetrafluoroethylene graft is safe and durable for symptomatic patients with chronic common carotid artery occlusion. The results of this study should be confirmed with a larger, randomized controlled trial in future.

17.
Microbiol Resour Announc ; 8(45)2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31699763

RESUMO

This work reports the draft genome sequence of Agrobacterium tumefaciens strain 1D1526. The assembled genome is composed of a 2,881,823-bp circular chromosome, a 2,235,711-bp linear chromosome, and a 44,582-bp unassembled contig.

18.
Clin Interv Aging ; 14: 1763-1769, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31695346

RESUMO

Background: Critically ill older patients with acute kidney injury (AKI), also referred to as acute renal failure, are associated with high in-hospital mortalities. Preexisting malnutrition is highly prevalent among AKI patients and increases in-hospital mortality rate. This study is to evaluate the predictive power of some serum nutritional related biomarkers predicting the 90 days in-hospital mortality of critically ill older patients with AKI. Methods: A prospective, observational study was conducted in a university teaching hospital. One hundred and five critically ill older patients with AKI aged 60-95 were enrolled and were divided into survival group (n=44) and non-survival group (n=61) in the light of their final outcomes. Receiver operating characteristic analyses (ROC) were performed to calculate the area under ROC curve (AUC). Sensitivity and specificity of in-hospital mortality prediction were calculated. Results: Significant differences were found between the survival group and non-survival group of critically ill older patients with AKI. AUC of low density lipoprotein (LDL) and albumin were 0.686 and 0.595, respectively. The asymptotic 95% confidence intervals of LDL and albumin were 0.524-0.820 and 0.488-0.696, respectively. Sensitivity of the 90 days in-hospital mortality prediction of LDL and albumin were 68.71% and 69.09%, respectively. Specificity of 90 days in-hospital mortality prediction of LDL and albumin were 69.23% and 50.0%, respectively. Conclusion: LDL and albumin did not have sufficient power to predict the 90 days in-hospital mortality of critically ill older patients with AKI. Further research on the association between malnutrition and poor prognosis of critically ill older patients with AKI is needed in the future.Trial registration: ClinicalTrials.gov identifier: NCT00953992.


Assuntos
Lesão Renal Aguda/sangue , Lesão Renal Aguda/mortalidade , Mortalidade Hospitalar , Lipoproteínas LDL/sangue , Albumina Sérica/metabolismo , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Estado Terminal/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Curva ROC
19.
Neuron ; 104(5): 1010-1021.e10, 2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31607423

RESUMO

Perceptual decisions are often based on multiple sensory inputs whose reliabilities rapidly vary over time, yet little is known about how the brain integrates these inputs to optimize behavior. The optimal solution requires that neurons simply add their sensory inputs across time and modalities, as long as these inputs are encoded with an invariant linear probabilistic population code (ilPPC). While this theoretical possibility has been raised before, it has never been tested experimentally. Here, we report that neural activities in the lateral intraparietal area (LIP) of macaques performing a vestibular-visual multisensory decision-making task are indeed consistent with the ilPPC theory. More specifically, we found that LIP accumulates momentary evidence proportional to the visual speed and the absolute value of vestibular acceleration, two variables that are encoded with close approximations to ilPPCs in sensory areas. Together, these results provide a remarkably simple and biologically plausible solution to near-optimal multisensory decision making.

20.
J Investig Med ; 67(8): 1103-1109, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31575668

RESUMO

Although significant improvements have been achieved in the renal replacement therapy of acute kidney injury (AKI), the mortality of patients with AKI remains high. The aim of this study is to prospectively investigate the capacity of Acute Physiology and Chronic Health Evaluation version II (APACHE II), Simplified Acute Physiology Score version II (SAPS II), Sepsis-related Organ Failure Assessment (SOFA) and Acute Tubular Necrosis Individual Severity Index (ATN-ISI) to predict in-hospital mortality of critically ill patients with AKI. A prospective observational study was conducted in a university teaching hospital. 189 consecutive critically ill patients with AKI were selected according Risk, Injury, Failure, Loss, or End-stage kidney disease criteria. APACHE II, SAPS II, SOFA and ATN-ISI counts were obtained within the first 24 hours following admission. Receiver operating characteristic analyses (ROCs) were applied. Area under the ROC curve (AUC) was calculated. Sensitivity and specificity of in-hospital mortality prediction were calculated. In this study, the in-hospital mortality of critically ill patients with AKI was 37.04% (70/189). AUC of APACHE II, SAPS II, SOFA and ATN-ISI was 0.903 (95% CI 0.856 to 0.950), 0.893 (95% CI 0.847 to 0.940), 0.908 (95% CI 0.866 to 0.950) and 0.889 (95% CI 0.841 to 0.937) and sensitivity was 90.76%, 89.92%, 90.76% and 89.08% and specificity was 77.14%, 70.00%, 71.43% and 71.43%, respectively. In this study, it was found APACHE II, SAPS II, SOFA and ATN-ISI are reliable in-hospital mortality predictors of critically ill patients with AKI. Trial registration number: NCT00953992.

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