Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.214
Filtrar
1.
Artigo em Inglês | MEDLINE | ID: mdl-32569620

RESUMO

The neurodevelopmental hypothesis of schizophrenia has been widely accepted. In light of our previous microarray data, two neurodevelopment-related genes were focused on inclduing the N-acylsphingosine amidohydrolase 1 gene (ASAH1) and the nerve growth factor gene (NGF). The evidence that ASAH1 and NGF are associated with schizophrenia is far from conclusive. Furthermore, their interactions in schizophrenia have not been investigated. Total 413 patients and 578 controls were included. Eleven single-nucleotide polymorphisms (SNPs) in ASAH1 and NGF were selected. A multifactor dimensionality reduction (MDR) was applied to investigate gene-gene interactions in schizophrenia, and the traditional odds ratio methods was applied to validate it. The effects of ASAH1, NGF and their interaction on the severity of the disease were analyzed by 3 × 3 covariance analysis of (ANCOVA). The biological interaction between ASAH1 and NGF was examined. KEGG was used to identify the related signaling pathways. After correction by Bonferroni, there were no differences in the genotypic, allelic, or haplotypic frequencies of 11 SNPs between patients and controls. However, the interaction of certain SNPs had effect on susceptibility to schizophrenia, including two high-risk and one low-risk genotypic combinations (OR = 1.49 [1.11-2.00]; OR = 1.45 [1.09-1.92], and OR = 0.64 [0.41-0.98]). ASAH1-rs7830490 and its interaction with NGF-rs4332358 were associated with the general psychopathological subscale score (F adjusted = 3.94, p adjusted = 0.01; F adjusted = 2.36, p adjusted = 0.03). We also found that ASAH1 and NGF interacted with CaMK2B involving in the neurotrophin signaling pathway. Our results suggest that the interaction of ASAH1 and NGF with CaMK2B involved in neurotrophin signaling pathway may contribute to schizophrenia susceptibility and psychopathology.

2.
Food Chem ; 335: 127633, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-32739813

RESUMO

The influence of different fatty acid carbon chains on the kinetic interactions of nanocomplexes between esterified astaxanthin (E-Asta) and ß-lactoglobulin (ß-Lg) were investigated by multi-spectroscopy and molecular modeling techniques. We synthesized ten different E-Asta bound to ß-Lg and formed nanocomplexes (< 300 nm). Fluorescence spectroscopy showed moderate affinities (binding constants Ka = 103-104 M-1). Docosahexaenoic acid astaxanthin monoester (Asta-C22:6) had the strongest binding affinity towards ß-Lg (Ka = 3.77 × 104 M-1). The fluorescence quenching of ß-Lg upon binding of E-Asta displayed a static mechanism, with binding sites (n) equal to 1. Fourier transform infrared spectroscopy and ultraviolet-visible absorption spectroscopy revealed that E-Asta might enter the ß-Lg hydrophobic cavity, leading to unfolding of the peptide chain skeleton. In summary, ß-Lg and E-Asta can form stable nanocomplex emulsions to achieve an effective delivery process for E-Asta.

3.
Chin Med J (Engl) ; 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33031138

RESUMO

BACKGROUND: Estrogen is involved in the pathophysiological process of benign prostatic hyperplasia (BPH), in which epithelial-mesenchymal transition (EMT) plays an important role. Upregulation of aquaporin (AQP) 5, which is directly activated by estrogen, has been reported to promote EMT in multiple cells. This study aimed to examine the effects of AQP5 on estrogen-induced EMT in the prostate. METHODS: Normal prostate (NP) tissue samples without any histopathological changes and BPH tissue samples with pathologically confirmed hyperplasia were obtained. An EMT cell model was subsequently established by adding estradiol (E2) to RWPE-1 cells, after which AQP5 knockdown was performed. Tissue morphological and immunohistochemical features were examined using hematoxylin-eosin and immunohistochemical staining. Western blot analysis was performed to determine the expression of AQPs, estrogen receptors, and EMT-related proteins. Cell proliferation was assessed and supernatants were collected for enzyme-linked immunosorbent assay to determine transforming growth factor-ß1 (TGF-ß1) concentrations. Immunofluorescence staining was performed to assess protein expressions in RWPE-1 cells. RESULTS: BPH tissues exhibited greater EMT (TGF-ß1: 1.362 ±â€Š0.196 vs. 0.107 ±â€Š0.067, P = 0.003; vimentin: 1.581 ±â€Š0.508 vs. 0.221 ±â€Š0.047, P < 0.001; E-cadherin: 0.197 ±â€Š0.188 vs. 1.344 ±â€Š0.088, P < 0.001), higher AQP5 (1.268 ±â€Š0.136 vs. 0.227 ±â€Š0.055, P < 0.001) and estrogen receptor (ER) α (1.250 ±â€Š0.117 vs. 0.329 ±â€Š0.134, P < 0.001) expression but lower ERß (0.271 ±â€Š0.184 vs. 1.564 ±â€Š0.130, P < 0.001) expression than NP tissues. E2-stimulated cells had higher AQP5 expression (1.298 ±â€Š0.058 vs. 1.085 ±â€Š0.104, P = 0.049), increased cell proliferation (1.510 ±â€Š0.089 vs.1.000 ±â€Š0.038, P < 0.001), and EMT (TGF-ß1 concentration: 0.352 ±â€Š0.021 ng/mL vs. 0.125 ±â€Š0.014 ng/mL, P < 0.001; vimentin: 1.641 ±â€Š0.120 vs. 0.188 ±â€Š0.020, P = 0.002; E-cadherin: 0.075 ±â€Š0.030 vs. 0.843 ±â€Š0.046, P < 0.001) than controls. E2-stimulated cells with AQP5 knockdown exhibited decreased EMT (TGF-ß1 concentration: 0.223 ±â€Š0.041 ng/mL vs. 0.352 ±â€Š0.021 ng/mL, P = 0.016; vimentin: 0.675 ±â€Š0.056 vs. 1.641 ±â€Š0.120, P = 0.001; E-cadherin: 0.159 ±â€Š0.037 vs. 0.075 ±â€Š0.030, P = 0.040) than E2-stimulated cells with non-related siRNA. CONCLUSION: Our findings suggest that estrogen induces BPH possibly by promoting AQP5 expression. Hence, AQP5 might be a novel target for modulating EMT in prostate epithelial cells.

4.
Medicine (Baltimore) ; 99(41): e22610, 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33031318

RESUMO

BACKGROUND: We systematically evaluated the evidences on oncological and functional outcomes of high-intensity focused ultrasound (HIFU) as the primary treatment for localized prostate cancer (PCa). METHODS: A systematic review was used Medline, Embase, and the Cochrane Library from the inception of each database. The review analyzed the oncological and functional outcomes of HIFU in the treatment of PCa. The RevMan 5.3 software was used for quantity analysis incidence of complications. RESULTS: Twenty-seven articles were included for analysis with a total of 7393 patients. Eighteen studies investigated the whole-gland HIFU, and the duration of follow-up ranged from 2 to 168 months. After whole-gland HIFU, the mean prostate-specific antigen (PSA) nadir was found to be 0.4 to 1.95 ng/mL and the mean time to PSA nadir was 2.4 to 5.4 months. The rate of positive biopsy after HIFU was 4.5% to 91.1%. Meta-analysis revealed the incidences of urinary incontinence, impotence, urinary obstruction, retention, and infection was 10%, 44%, 15%, 11%, 7%, respectively. Nine studies investigated partial-gland HIFU, and the duration of follow-up was 1 to 131 months. After partial-gland HIFU, the mean PSA nadir was 1.9 to 2.7 ng/mL and the mean time to PSA nadir 5.7 to 7.3 months. The rate of positive biopsy after HIFU in the treatment area was 14% to 37.5%. Meta-analysis revealed the incidences of urinary incontinence, impotence, urinary obstruction, retention, and infection was 2%, 21%, 2%, 9%, 11%, respectively. CONCLUSIONS: Early evidence suggested the partial-gland HIFU was safer than whole-gland HIFU, and they had similar oncological outcomes. More prospective randomized controlled trials of whole-gland and partial-gland HIFU for PCa was needed.

6.
Microbiol Immunol ; 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33034909

RESUMO

It has been reported that High mobility group nucleosomal binding domain 2 (HMGN2) is a nucleus-related protein to regulate gene transcription and plays a critical role in bacterial clearance. We have demonstrated that an elevated level of HMGN2 reduced integrin α5/ß1 expression of human pulmonary epithelial A549 cells during Klebsiella pneumoniae infection, thus weakening bacteric adhesion and invasion. However, the mechanism of how HMGN2 regulates integrin expression remains unclear. In this study, we found that a transcription factor-Nuclear factor I (NFI), which served as the potential target of HMGN2 to regulate integrin expression. Our results showed that HMGN2 was able to promote NFIA and NFIB expression by increasing H3K27 acetylation of NFIA/B promoter regions. The integrin α5/ß1 expression was significantly enhanced by knockdown of NFIA/B via siRNA approach. Meanwhile, NFIA/B silence could also compromise the inhibition effect of HMGN2 on the integrin α5/ß1 expression. Mechanistically, we demonstrated that HMGN2 facilitated the recruitment of NFI on the promoter regions of integrin α5/ß1 according to the Chromatin immunoprecipitation assay. In addition, we further demonstrated that the knockdown of NFIA/B induced more adhesion of Klebsiella pneumoniae on pulmonary epithelial A549 cells, which could be reversed by the application of an integrin inhibitor RGD. Our results revealed a regulatory role of HMGN2 on the transcription level of integrin α5/ß1, indicating a potential treatment strategy against Klebsiella pneumoniae-induced lung infectious diseases. This article is protected by copyright. All rights reserved.

7.
Sci Rep ; 10(1): 16325, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33004934

RESUMO

The diagnosis of tuberculous pericarditis (TBP) remains challenging. This prospective study evaluated the diagnostic value of Xpert MTB/RIF (Xpert) and T-SPOT.TB and adenosine deaminase (ADA) for TBP in a high burden setting. A total of 123 HIV-negative patients with suspected TBP were enrolled at a tertiary referral hospital in China. Pericardial fluids were collected and subjected to the three rapid tests, and the results were compared with the final confirmed diagnosis. Of 105 patients in the final analysis, 39 (37.1%) were microbiologically, histopathologically or clinically diagnosed with TBP. The sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio (DOR) for Xpert were 66.7%, 98.5%, 96.3%, 83.3%, 44.0, 0.338, and 130.0, respectively, compared to 92.3%, 87.9%, 81.8%, 95.1%, 7.6, 0.088, and 87.0, respectively, for T-SPOT.TB, and 82.1%, 92.4%, 86.5%, 89.7%, 10.8, 0.194, and 55.8, respectively, for ADA (≥ 40 U/L). ROC curve analysis revealed a cut-off point of 48.5 spot-forming cells per million pericardial effusion mononuclear cells for T-SPOT.TB, which had a DOR value of 183.8, while a cut-off point of 41.5 U/L for ADA had a DOR value of 70.9. Xpert (Step 1: rule-in) followed by T-SPOT.TB [cut-off point] (Step 2: rule-out) showed the highest DOR value of 252.0, with only 5.7% (6/105) of patients misdiagnosed. The two-step algorithm consisting of Xpert and T-SPOT.TB could offer rapid and accurate diagnosis of TBP.

8.
Chemosphere ; 264(Pt 1): 128427, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-33002800

RESUMO

Eleven years (2005-2015) of data from long-term monitoring at a Japanese remote background site in Wajima, were analyzed to investigate temporal trends and sources. Water-soluble inorganic ions (WSIIs) were analyzed for aerosol chemical composition. The total WSIIs concentration was 7.93 ± 3.93 µg/m3, accounting for 42.3% of TSP mass, ranged from 11.4 to 93.9%. SO42- is the most abundant ion, contributing a total WSII mass from 18.0 to 79.8%, and non-sea-salt (nss-) SO42- contributed from 63.6% to 99.6% of total SO42-, which was related to human activities on the Asian continent and the effects of marine precursors in spring and summer, respectively. NO3- and NH4+ contribute 6.3 and 7.4% of the total WSIIs and were affected by long-range transport and local sources as well. The increasing trend of Na+ and Cl- indicates the increased influence of sea salt, which is caused by more frequent strong winds. K+ is mainly produced from biomass burning with a stable seasonal variation, Ca2+ as the characteristic ion of dust has the highest concentration in spring. Mg2+ comes from minerals and marine sources during spring and summer, respectively. This work describes in detail the annual change trend of the WSIIs of atmospheric particles in the Wajima area, seasonal characteristics, and source contributions, provide a comprehensive understanding of long-term variation in atmospheric particulate.

9.
Food Chem ; 341(Pt 1): 128163, 2020 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-33035853

RESUMO

Lactic acid bacteria fermentation is a safe and green technology that can modify the function of food ingredients (including proteins). In this article, egg yolks were subjected to fermentation with commercial lactic acid bacteria for 0, 3, 6 and 9 h, respectively. After fermentation treatment, the microbial composition has changed obviously (Streptococcus thermophilus increased significantly). The free sulfhydryl group (SH) contents and surface hydrophobicity of egg yolk proteins were significantly reduced. The rheological results indicated that the treated egg yolks possessed a decreased apparent viscosity. Correspondingly, the emulsifying activity of egg yolk was enhanced from 9.07 to 19.55, 23.40 and 24.61 m2/g for 3, 6 and 9 h of fermentation, respectively. And the emulsifying stability reached the maximum after 3 h of fermentation. This study investigated the relationship between structure and properties of yolk proteins, and showed that lactic acid fermentation endued egg yolk with better emulsifying properties.

10.
Food Chem ; 341(Pt 2): 128202, 2020 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-33038806

RESUMO

Parboiled rice has high nutritional value but unpleasant palatability. In this study, rice stickiness was significantly reduced by steaming during the parboiling process; however, continuing steaming past certain durations no longer affected rice stickiness. It was also found: (i) the degree of starch gelatinization (DSG) increases and starch crystallinity decreases with increasing steaming time; (ii) the molecular size and chain length distribution (CLD) of leached starch for both white and parboiled rice are significantly different from those of native starch; (iii) the relation between leached amylopectin amount and rice stickiness explains the reduced stickiness by parboiling; and (iv) starch gelatinization in the surface layer of rice grains during parboiling might be critically important in blocking starch leaching, consequently leading to a less sticky texture. This study supplies a way to manage glutinous rice stickiness by parboiling for the production of non-sticky rice foods.

11.
J Sci Food Agric ; 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33063347

RESUMO

BACKGROUND: Astaxanthin (Asta) is widely used in the nutraceutical and food industry because of its strong antioxidant properties. However, natural Asta mainly exists in esterified form with various fatty acid chains, making it difficult to understand the particular molecular structure of astaxanthin esters (Asta-Es) that have better antioxidant capacity. In this study, Asta-Es with different molecular structures were systematically prepared, and identified by using TLC, UV-vis, HPLC-MS/MS, and 1 H-NMR. In addition, their antioxidant properties were evaluated by DPPH and ABTS scavenging activity. RESULTS: Fourteen Asta-Es with different molecular structures were systematically synthesized. This study used a simple and efficient method for the separation and purification of Asta-ME and Asta-DE with high purity (86%-94%) by silica gel column chromatography. 13-cis-Asta-E and 9-cis-Asta-E were firstly identified from Asta-E. The DPPH clearance rates and ABTS scavenging rates of Asta-C4:0, Asta-C8:0, Asta-C12:0, and Asta-C18:0 were relatively close, but the DPPH and ABTS scavenging rates of Asta-C18:0, Asta-C18:1, Asta-C18:2, and Asta-C22:6 increased gradually. Among all Asta-Es, Asta-C22:6/C22:6 showed the highest antioxidant capacity, with the DPPH and ABTS scavenging rates of 77.22 ± 3.29 % and 51.84 ± 1.65 %, respectively. CONCLUSION: In this study, it was concluded that chemically synthesized Asta-Es contained cis-astaxanthin ester and polyunsaturated fatty acid chain increased the antioxidant activity of Asta, showing less effect of the length of fatty acid chain. These results provide useful information for the production and use of highly efficient Asta-E as functional food and pharmaceutical ingredients. This article is protected by copyright. All rights reserved.

12.
J Food Sci ; 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33067851

RESUMO

Antarctic krill oil (AKO) is usually encapsulated by the protein materials, enhancing its oxidative stability. Proteins exhibit immense effect on lipid oxidation and induce protein-lipid co-oxidation. This study aimed at elucidating the co-oxidation mechanism of AKO and whey protein (WP) or myofibrillar protein (MP) in oil-in-water emulsions. The estimations of malondialdehyde (MDA) content, phospholipid molecular species, and pyrrole content resulted in increased and decreased oxidation rate of AKO (especially phosphatidylethanolamine) by WP and MP, respectively. Meanwhile, protein concentration, sulfhydryl content, the loss of tryptophan fluorescence intensity, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis results demonstrated that AKO promoted WP oxidation but inhibited MP oxidation. Further, the antioxidative abilities of seven common antioxidants were evaluated. Ascorbyl palmitate showed the most substantial antioxidative effect for both AKO and proteins (about 70% decrease of MDA content and 30% decrease of the decrease ratio of tryptophan fluorescence intensity). This finding supported that different proteins could exhibit different pro/anti-oxidative effects on lipid oxidation, especially for marine lipids abundant in phospholipids and polyunsaturated fatty acids. Besides, MP could also act as antioxidant in MP AKO emulsions, further extending its application from traditional surfactants. PRACTICAL APPLICATION: AKO is usually encapsulated by the protein materials, enhancing its oxidative stability. The results demonstrated MP could inhibit AKO oxidation, and vice versa, especially when ascorbyl palmitate was added at the same time. As a result, this finding explored a new potential wall material with antioxidative ability for the encapsulated products of AKO.

13.
Chembiochem ; 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-33051959

RESUMO

Functional nucleic acids (FNAs) are garnering tremendous interest owing to their high modularity and unique bioactivity. Three-dimensional FNAs have been developed to overcome the issues of nuclease degradation and limited cell uptake. We herein developed a new facile approach to the synthesis of multiple three-dimensional FNA nanostructures by harnessing photo-polymerization-induced self-assembly. Sgc8 aptamer and CpG oligonucleotide were modified as macro chain transfer reagents to mediate in situ polymerization and self-assembly. Diverse structures, including micelles, rods, and short worms, afford these two FNAs with higher nuclease resistance from serum, greater cellular uptake efficiency, and increased bioactivity.

14.
Eur J Neurol ; 2020 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-33070405

RESUMO

BACKGROUND: Spinocerebellar ataxia type 2 (SCA2) is the second most common type of SCAs in China. However, the clinical and genetic features of Chinese SCA2 patients were scarcely reported. METHODS: A total of 135 SCA2 individuals from 92 families and 104 unrelated normal individuals were recruited from three medical centers between 2008 and 2020. Sanger sequencing and TA cloning were used to determine the CAG repeat size and intrinsic structure. Clinical data of SCA2 patients including electromyography, magnetic resonance imaging, positron emission tomography and clinical scales was recorded. RESULTS: Mean age at onset (AAO) of SCA2 patients was 32.6 ± 11.9 years and corresponding CAG repeat length was 42.1 ± 3.6. CAG repeat length accounted for 64% of the AAO variance. We first observed that the patients had a significantly lower proportion of (CAG)8 CAA(CAG)4 CAA(CAG)8 within normal alleles than normal individuals (48.8% vs 64.9%, P=0.003), while that of (CAG)13 CAA (CAG)8 had an opposite distribution. Peripheral neuropathy was frequent, accounting for 75.9%. Parkinsonism was relatively common with a frequency of 11.8%. Two patients with parkinsonism showed a significantly more severe reduction of dopamine transporter level in the bilateral striatum than one with pure ataxia. An infantile-onset case with over 180 CAG repeats was characterized by global development delay, hypotonia and hearing impairment. CONCLUSIONS: This study exhibits genetic profile and clinical characteristics of the largest SCA2 cohort hitherto in the Chinese population, and analyzes inter-population differences. Many aspects of our population were different from other populations.

15.
Int J Prod Econ ; : 107956, 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33071462

RESUMO

Scholars and practitioners have recognized the importance of supply chain (SC) resilience. However, it remains unclear how to build SC resilience and whether SC resilience can enhance firm performance and bring values to customers. By analyzing data collected from 206 manufacturers in China, this study empirically examines how firms implement different information technology patterns (exploitative versus explorative) with SC patterns to achieve supplier and customer resilience from information processing theory, and examines the performance implications of these two dimensions of SC resilience. In addition, this study also investigates how information technology (IT) ambidexterity reconciles the paradox between IT exploitation and IT exploration in enhancing SC resilience. The results show that both supplier and customer resilience could improve SC performance. To achieve the two aspects of SC resilience, only explorative use of IT with suppliers and customers have significant effects. The results also show that the ambidextrous use of IT on the customer side takes effect. The exploitative and explorative use of IT complement each other to improve customer resilience. The findings of this study contribute to IT and SC resilience literature.

16.
Acta Crystallogr C Struct Chem ; 76(Pt 9): 856-862, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32887855

RESUMO

The chemistry of transition-metal complexes with unusually high coordination numbers has been of interest because of their application in catalytic and biological systems. Deprotonation of the ionogenic tetradentate ligand 6,6'-bis(1H-tetrazol-5-yl)-2,2'-bipyridine [H2bipy(ttr)2] in the presence of iron(III) and tetra-n-butylammonium bromide, [n-Bu4N]Br, in solution resulted in the synthesis of a rare octacoordinated anionic mononuclear complex, tetra-n-butylammonium bis[6,6'-bis(tetrazol-1-id-5-yl)-2,2'-bipyridine]iron(III) methanol hemisolvate dihydrate, (C16H36N)[Fe(C12H6N10)2]·0.5CH3OH·2H2O or [n-Bu4N][Fe{bipy(ttr)2}2]·0.5CH3OH·2H2O (1), which has been structurally characterized by elemental analysis, powder X-ray diffraction (PXRD) and single-crystal X-ray diffraction. In 1, the coordination sphere of the iron(III) ion is a distorted bis-disphenoid dodecahedron, in which the eight coordination positions are occupied by eight N atoms from two independent tetradentate [bipy(ttr)2]2- anionic ligands, therefore forming the anionic [Fe{bipy(ttr)2}2]- unit, with the negative charge balanced by a free [n-Bu4N]+ cation. An investigation of the magnetic properties of 1 revealed a gradual incomplete spin-crossover behaviour below 150 K.

17.
Neurobiol Aging ; 2020 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-32893042

RESUMO

This study was to investigate the genetic contribution of optineurin (OPTN), a gene associated with primary open-angle glaucoma and amyotrophic lateral sclerosis (ALS), in Chinese patients with ALS. To gain additional insight into the spectrum and pathogenic relevance of this gene for ALS, we sequenced all the coding exons of OPTN and intron-exon boundaries in 398 patients with ALS [33 familial ALS (FALS), 365 unrelated sporadic ALS (SALS)] using next-generation sequencing. Six nonsynonymous variants were identified in 6 unrelated patients with SALS, in which one patient harbored 2 different OPTN variants and another carried an SETX mutation at the same time. Among those 6 variants, 4 were novel missense mutations: c.247C>T (p.R83C), c.676T>C (p.F226L), c.1699A>G (p.Y567A), and c.1713C>G (p.H571Q) (all heterozygous). The remaining 2 were already reported in previous studies. All 6 patients were spinal onset but showed differences in ALS subtypes as well as age of onset and disease progression. Taken together, we detected 4 novel missense OPTN mutations and 2 previously described mutations that might be causal for ALS, accounting for a mutant frequency of 1.10% (4/365) in patients with SALS after excluding 2 benign variants, and confirmed that OPTN mutations are common in Asian populations. In addition, our data suggested that variability in phenotype of the same mutation might partly be due to the oligogenic basis of ALS.

18.
Sci China Life Sci ; 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32880864

RESUMO

Host-pathogen interactions in the setting of chronic pulmonary inflammation remain unclear, and the occurrence of pneumonia is increased in patients with chronic obstructive pulmonary disease who use immunosuppressive drugs. We performed Acinetobacter baumannii infection in mice with chronic pulmonary inflammation after intranasal administration of SiO2 and found SiO2 treatment increased host defense against A. baumannii infection. Innate immune responses initiated by NF-κB, type 1 interferon, NLRP3 and AIM2 inflammasomes were dispensable for SiO2-mediated host defense. SiO2 treatment activated the mTORC1 signaling, and mTORC1 was crucial for host defense against A. baumannii infection. Our study highlights the protective role of mTORC1 signaling in host defense against bacterial infection, offers novel insights into understanding the mechanisms of immunosuppressive drug-related pneumonia, and provides potential host-directed therapeutics to treat bacterial infections.

19.
20.
Urol J ; 2020 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-32869260

RESUMO

PURPOSE: Alpha-blockers have been proven as an effective method for increasing the stone expulsion rate of distal ureteral stones. Limited studies have focused on doxazosin; its efficacy remained unclear. We performed this meta-analysis to investigate the efficacy and safety of doxazosin for patients diagnosed with distal ureteral stones less than 10mm. MATERIALS AND METHODS: We systematically searched Ovid MEDLINE®, Cochrane Library, EMBASE, and PubMed for articles comparing doxazosin and conventional care or tamsulosin for distal ureteral stones through October 2019. The outcome measures were stone expulsive rate (SER), stone expulsive time (SET), pain episodes, analgesics consumption, and adverse events. RESULTS: We included 12 studies involving 836 participants with distal ureteral stones less than 10mm in our review. The present meta-analysis showed doxazosin could significantly increase SER [RR=1.64,95%CI (1.32, 2.04), P  < 0.00001], shorten SET [WMD=-3.97,95% CI (-5.68, -2.27), P  < 0.00001] compared with conventional care. In the subgroup analyses, doxazosin showed no benefit in the children subgroup (<16 years old) [RR=1.63,95% CI (0.73,3.64), P  =0.23]. No statistically significant difference was observed regarding the effectiveness of doxazosin and tamsulosin in SER, SET, and safety. 9 in 286 participants reported doxazosin-related adverse events; most were mild to moderate. CONCLUSION: This meta-analysis may suggest that doxazosin is a safe and effective MET for distal ureteral stones less than 10mm. It is not demonstrated to have any significant difference with tamsulosin in SER, SET, and safety. However, it showed no benefits for patients<16 years old.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA