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1.
Hum Genet ; 2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33604698

RESUMO

SARS-CoV-2 is responsible for the coronavirus disease 2019 (COVID-19) and the current health crisis. Despite intensive research efforts, the genes and pathways that contribute to COVID-19 remain poorly understood. We, therefore, used an integrative genomics (IG) approach to identify candidate genes responsible for COVID-19 and its severity. We used Bayesian colocalization (COLOC) and summary-based Mendelian randomization to combine gene expression quantitative trait loci (eQTLs) from the Lung eQTL (n = 1,038) and eQTLGen (n = 31,784) studies with published COVID-19 genome-wide association study (GWAS) data from the COVID-19 Host Genetics Initiative. Additionally, we used COLOC to integrate plasma protein quantitative trait loci (pQTL) from the INTERVAL study (n = 3,301) with COVID-19 loci. Finally, we determined any causal associations between plasma proteins and COVID-19 using multi-variable two-sample Mendelian randomization (MR). The expression of 18 genes in lung and/or blood co-localized with COVID-19 loci. Of these, 12 genes were in suggestive loci (PGWAS < 5 × 10-05). LZTFL1, SLC6A20, ABO, IL10RB and IFNAR2 and OAS1 had been previously associated with a heightened risk of COVID-19 (PGWAS < 5 × 10-08). We identified a causal association between OAS1 and COVID-19 GWAS. Plasma ABO protein, which is associated with blood type in humans, demonstrated a significant causal relationship with COVID-19 in the MR analysis; increased plasma levels were associated with an increased risk of COVID-19 and, in particular, severe COVID-19. In summary, our study identified genes associated with COVID-19 that may be prioritized for future investigations. Importantly, this is the first study to demonstrate a causal association between plasma ABO protein and COVID-19.

2.
Radiology ; 298(3): 695-703, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33529137

RESUMO

Background To reduce adverse effects of whole-gland therapy, participants with localized clinically significant prostate cancer can undergo MRI-guided focal therapy. Purpose To explore safety and early oncologic and functional outcomes of targeted focal high-intensity focused ultrasound performed under MRI-guided focused ultrasound for intermediate-risk clinically significant prostate cancer. Materials and Methods In this prospective phase II trial, between February 2016 and July 2019, men with unifocal clinically significant prostate cancer visible at MRI were treated with transrectal MRI-guided focused ultrasound. The primary end point was the 5-month biopsy (last recorded in December 2019) with continuation to the 24-month follow-up projected to December 2021. Real-time ablation monitoring was performed with MR thermography. Nonperfused volume was measured at treatment completion. Periprocedural complications were recorded. Follow-up included International Prostate Symptom Score (IPSS) and International Index of Erectile Function-15 (IIEF-15) score at 6 weeks and 5 months, and multiparametric MRI and targeted biopsy of the treated area at 5 months. The generalized estimating equation model was used for statistical analysis, and the Holm method was used to adjust P value. Results Treatment was successfully completed in all 44 men, 36 with grade group (GG) 2 and eight with GG 3 disease (median age, 67 years; interquartile range [IQR], 62-70 years). No major treatment-related adverse events occurred. Forty-one of 44 participants (93%; 95% CI: 82, 98) were free of clinically significant prostate cancer (≥6 mm GG 1 disease or any volume ≥GG 2 disease) at the treatment site at 5-month biopsy (median, seven cores). Median IIEF-15 and IPSS scores were similar at baseline and at 5 months (IIEF-15 score at baseline, 61 [IQR, 34-67] and at 5 months, 53 [IQR, 24-65.5], P = .18; IPSS score at baseline, 3.5 [IQR, 1.8-7] and at 5 months, 6 [IQR, 2-7.3], P = .43). Larger ablations (≥15 cm3) compared with smaller ones were associated with a decline in IIEF-15 scores at 6 weeks (adjusted P < .01) and at 5 months (adjusted P = .07). Conclusion Targeted focal therapy of intermediate-risk prostate cancer performed with MRI-guided focused ultrasound ablation was safe and had encouraging early oncologic and functional outcomes. © RSNA, 2021 Online supplemental material is available for this article See also the editorial by Tempany-Afdhal in this issue.

3.
Free Radic Biol Med ; 165: 385-394, 2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33581276

RESUMO

Sestrin2 (Sesn2) is a stress-inducible protein that plays a critical role in the response to ischemic stress. We recently recognized that Sesn2 may protect the heart against ischemic insults by reducing the generation of reactive oxygen species (ROS). After 45 min of ischemia followed by 24 h of reperfusion, myocardial infarcts were significantly larger in Sesn2 KO hearts than in wild-type hearts. Isolated cardiomyocytes from wild-type hearts treated with hypoxia and reoxygenation (H/R) stress showed significantly greater Sesn2 levels, compared with normoxic hearts (p < 0.05). Intriguingly, the administration of adeno-associated virus 9-Sesn2 into Sesn2 knockout (KO) hearts rescued Sesn2 protein levels and significantly improved the cardiac function of Sesn2 KO mice exposed to ischemia and reperfusion. The rescued levels of Sesn2 in Sesn2 KO hearts significantly ameliorated ROS generation and the activation of ROS-related stress signaling pathways during ischemia and reperfusion. Moreover, the rescued Sesn2 levels in Sesn2 KO cardiomyocytes improved the maximal velocity of cardiomyocyte shortening by H/R stress. Rescued Sesn2 levels also improved peak height, peak shortening amplitude, and maximal velocity of the re-lengthening of Sesn2 KO cardiomyocytes subjected to H/R. Finally, the rescued Sesn2 levels significantly augmented intracellular calcium levels and reduced the mean time constant of transient calcium decay in Sesn2 KO cardiomyocytes exposed to H/R. Overall, these findings indicated that Sesn2 can act as an endogenous antioxidant to maintain intracellular redox homeostasis under ischemic stress conditions.

4.
Exp Neurol ; 339: 113646, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33600817

RESUMO

Spliced X-box binding protein-1 (XBP1s) together with the hexosamine biosynthetic pathway (HBP) and O-GlcNAcylation forms the XBP1s/HBP/O-GlcNAc axis. Our previous studies have provided evidence that activation of this axis is neuroprotective after ischemic stroke and critically, ischemia-induced O-GlcNAcylation is impaired in the aged brain. However, the XBP1s' neuroprotective role and its link to O-GlcNAcylation in stroke, as well as the therapeutic potential of targeting this axis in stroke, have not been well established. Moreover, the mechanisms underlying this age-related impairment of O-GlcNAcylation induction after brain ischemia remain completely unknown. In this study, using transient ischemic stroke models, we first demonstrated that neuron-specific overexpression of Xbp1s improved outcome, and pharmacologically boosting O-GlcNAcylation with thiamet-G reversed worse outcome observed in neuron-specific Xbp1 knockout mice. We further showed that thiamet-G treatment improved long-term functional recovery in both young and aged animals after transient ischemic stroke. Mechanistically, using an analytic approach developed here, we discovered that availability of UDP-GlcNAc was compromised in the aged brain, which may constitute a novel mechanism responsible for the impaired O-GlcNAcylation activation in the aged brain after ischemia. Finally, based on this new mechanistic finding, we evaluated and confirmed the therapeutic effects of glucosamine treatment in young and aged animals using both transient and permanent stroke models. Our data together support that increasing O-GlcNAcylation is a promising strategy in stroke therapy.

5.
Artigo em Inglês | MEDLINE | ID: mdl-33631343

RESUMO

Lead (Pb) pollution poses great threats to mammals including human and it is also hazardous to bird life. In this study, RNA sequencing analysis was employed to examine the molecular responses to lead exposure in the liver of a toxicological model species Japanese quails. Female birds were exposed to 0, 50, 500 and 1000 ppm waterborne Pb for 49 days. The results showed that hepatic microstructure was damaged under lead exposure featured by sinusoids dilation and irregularity as well as cell necrosis. Moreover, ultrastructural injury in the liver including mitochondrial swelling and vacuolization as well as nuclear deformation was induced by lead exposure. Lead exposure also caused the decrease of lipid droplets in the liver by oil red O staining. In addition, liver transcriptomic analysis revealed that molecular signaling and functional pathways were disrupted by lead exposure. Meanwhile, the expression of genes involved with hepatic glycerophospholipids metabolism of triglyceride synthesis and lipid transport of triglyceride transfer was significantly down-regulated by lead exposure. Moreover, the up-regulation of genes associated with fatty acid oxidation and the down-regulation of genes related with fatty acid synthesis were caused by lead exposure. The present study implied that lead induced liver malfunction and bird health risks through histopathological damages, molecular signaling disruption, genetic expression alteration and triglyceride metabolism disturbance.

6.
Artigo em Inglês | MEDLINE | ID: mdl-33631426

RESUMO

Genome-scale metabolomics analysis is increasingly used for pathway and function discovery in the post-genomics era. The great potential offered by developed mass spectrometry (MS)-based technologies has been hindered, since only a small portion of detected metabolites were identifiable so far. To address the critical issue of low identification coverage in metabolomics, we adopted a deep metabolomics analysis strategy by integrating advanced algorithms and expanded reference databases. The experimental reference spectra and in silico reference spectra were adopted to facilitate the structural annotation. To further characterize the structure of metabolites, two approaches were incorporated into our strategy, which were structural motif search combined with neutral loss scanning and metabolite association network. Untargeted metabolomics analysis was performed on 150 rice cultivars using ultra performance liquid chromatography-quadrupole-Orbitrap mass spectrometer. Consequently, a total of 1939 of 4491 metabolite features in MS/MS spectral tag (MS2T) library were annotated, representing an extension of annotation coverage by an order of magnitude on rice. The differential accumulation patterns of flavonoids between indica and japonica cultivars were revealed, especially O-sulfated flavonoids. A series of closely-related flavonolignans were characterized, adding further evidence for the crucial role of tricin-oligolignols in lignification. Our study provides a great template in the exploration of phytochemical diversity for more plant species.

7.
Neuroepidemiology ; : 1-9, 2021 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-33621971

RESUMO

BACKGROUND: Prior studies have suggested that head injury might be a potential risk factor of amyotrophic lateral sclerosis (ALS). However, the association has not been well established. We aimed to provide a synopsis of the current understanding of head injury's role in ALS. METHODS: We performed a systematic search in PubMed for observational studies that quantitatively investigated the association between head injury and ALS risk published before April 10, 2020. We used a random-effects model to calculate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Fourteen eligible articles including 10,703 cases and 2,159,324 controls were selected in current meta-analysis. We found that head injury was associated with an increased risk of ALS (OR = 1.38, 95% CI: 1.20-1.60) and the association was slightly stronger concerning severe head injury and ALS risk (OR = 1.69, 95% CI: 1.27-2.23). Considering the number of head injuries (N) and ALS risk, the association was weak (OR = 1.23, 95% CI: 1.10-1.37, N = 1; OR = 1.29, 95% CI: 0.89-1.86, N ≥ 2). In addition, a strong association with ALS risk was found in individuals who suffered head injury <1 year (OR = 4.05, 95% CI: 2.79-5.89), and when the time lag was set at 1-5, 5-10, and >10 years, the pooled OR was 1.13, 1.35, and 1.10, respectively. CONCLUSION: This meta-analysis indicates that head injury, especially severe head injury, could increase ALS risk. Although a strong association is found between head injury <1 year and ALS risk in the current study, this result suggests a possibility of reverse causation.

8.
J Sci Food Agric ; 2021 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-33608875

RESUMO

BACKGROUND: High carotenoids contents always led to a yellower/redder color of carrots, while a puzzling phenomenon still existed that freeze-dried carrots (FDC) had higher carotenoids contents but a lighter color compared with thermal-dried carrots. It seemed that carotenoid was not the only main factor that affected sample color. Hence, the discoloration characteristics of freeze-dried carrots were comprehensively analyzed from physical structure and color-related chemical compositions profiles. RESULTS: Outcomes of low field nuclear magnetic resonance and scanning electron microscope showed that sublimation of immobilized water preserved the intact porous structure of FDC, which kept the volume shrinkage less than 30% and led to less accumulations of color-related compositions. Besides, results of correlation and PCA-X model analysis proved that lutein and caffeic acid mainly affected a* value (r = 0.917) and b* value (r = 0.836) of FDC, respectively. Moreover, lipoxygenase indirectly affected sample color by degrading carotenoids, the lutein contents loss for fresh and blanching FDCs were 41.56% and 47.14%, respectively. CONCLUSONS: The discoloration of FDC was significantly affected by both of physical structure and color-related chemical compositions. This article is protected by copyright. All rights reserved.

10.
Biomed Res Int ; 2021: 8834795, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33575346

RESUMO

The positive effect of low-intensity pulsed ultrasound (LIPUS) on bone fracture healing has been proved. However, during the period of LIPUS therapy, it is undetermined whether LIPUS promotes the formation of heterotopic ossification (HO), which usually occurs in muscle tissues after trauma such as bone fracture and spinal cord injury. Here, we used 6-week LIPUS therapy in a 42-year-old Chinese male patient with a fracture nonunion in combination with ultrasonography for monitoring fracture healing and HO formation. After the LIPUS therapy, the mineralized bone formation in the area of defect of the distal tibia was presented in an ultrasound image, which was consistent with the outcome of plain radiography showing callus formation and the blurred fracture line in the area exposed to LIPUS. In addition, ultrasound images revealed no evidence of HO development within soft tissues during the period of LIPUS therapy. This study suggests that ultrasonography is a potential tool to guarantee the performance of LIPUS therapy with monitoring HO formation. Easy to use, the integration of the handheld ultrasound scanner and the ultrasonic therapeutic apparatus is entirely dedicated to help orthopedists make high-quality care and diagnosis.

11.
JAMA Oncol ; 2021 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-33538777

RESUMO

Importance: Phase 3 randomized clinical trials (RCTs) are usually reported after a predetermined number of events (death or disease progression) have occurred, when survival curves remain poorly defined. Updated reports are important in providing mature data. Objectives: To evaluate the proportion of phase 3 RCTs for cancer that are updated and the factors that are associated with updating them and, for updated trials, to compare initial and updated results. Design, Setting, and Participants: This study identified reports of 2-group RCTs with a sample size of at least 100, published in 6 major journals between 1990 and 2010, that evaluated drug treatments for breast, lung, or prostate cancer. PubMed and abstracts of large cancer conferences were searched to identify updated (or earlier) reports of the same trials published up to 2019. Logistic regression was used to identify factors associated with the provision of updated reports. The hazard ratios defining the relative treatment effects for the primary and secondary end points between the initial and updated reports were compared. Main Outcomes and Measures: Proportion of RCTs whose results are updated, factors associated with updating, and change in hazard ratio for the primary end point between initial and updated reports. Results: A total of 207 RCTs met the inclusion criteria, and 41 (20%) were found to have updated reports. The factors significantly associated with an update included positive trial results (odds ratio [OR], 8.7 [95% CI, 3.3-23.3]), larger trial size (OR, 1.0006 [95% CI, 1.0000-1.0012]), evaluation of hormonal agents (OR, 5.8 [95% CI, 1.6-21.8]) or targeted agents (OR, 4.3 [95% CI, 1.3-14.6]) compared with chemotherapy, and evaluation of adjuvant therapy rather than therapy for advanced disease (OR, 8.0 [95% CI, 2.9-21.9]). For 31 trials for which initial and updated hazard ratios for the primary end point were available, the median hazard ratio increased from 0.66 (95% CI, 0.22-1.20) to 0.74 (95% CI, 0.32-1.19) (P < .001), indicating a decreased level of effectiveness. Conclusions and Relevance: Only 20% of reports of phase 3 clinical trials for breast, lung, and prostate cancer were updated. Original reports of such trials are based on relatively few events, and their results are immature; more mature data indicate a decreased level of effect in updated trials. Updated reporting to provide mature, long-term results of clinical trials should be mandated.

12.
Nat Plants ; 7(2): 116-122, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33594263

RESUMO

Asia has a rich variety of nutritious 'neglected crops', domesticated since ancient times but mostly forgotten or underutilized today. These crops, including cereals, roots, nuts, pulses, fruits and vegetables, are adapted to their land, resilient to environmental challenges and rich in micronutrients. Changing current agricultural practices from a near monoculture to a diverse cropping portfolio that uses these forgotten crops is a viable and promising approach to closing the current gaps in production and nutrition in Asia. Such an approach was proposed by the Food and Agriculture Organization's Zero Hunger initiative in Asia, which aims to end hunger by 2030. The Zero Hunger initiative is a promising approach to help increase access to nutritious food; however, it faces substantial challenges, such as the lack of farmer willingness to switch crops and adequate governmental support for implementation. Countries such as Nepal have started using these neglected crops, implementing various approaches to overcome challenges and start a new agricultural pathway.

13.
Artigo em Inglês | MEDLINE | ID: mdl-33515746

RESUMO

OBJECTIVE: The incidence of adnexal masses in pregnancy is 1-6%. While surgery is often indicated, there are no definitive management guidelines. We aimed to investigate the optimal approach to surgical management of adnexal masses in pregnancy based on a meta-analysis of previous studies. DATA SOURCES: We performed a systematic review using MEDLINE, EMBASE, Cochrane Library, and Clinicaltrials.gov from inception to July 17, 2020. METHODS OF STUDY SELECTION: There were no restrictions on study type, language, or publication date. Comparative and non-comparative retrospective studies that reviewed operative techniques used in surgery of adnexal masses in pregnancy were included. Meta-analyses were performed to assess outcomes. This study was registered in Prospero (CRD42019129709). TABULATION, INTEGRATION, AND RESULTS: Comparative studies were identified for laparoscopy versus laparotomy and elective versus emergent surgery (11 and 4, respectively). Elective surgery is defined as a scheduled antepartum procedure. For laparoscopy versus laparotomy, the mean maternal age and gestational age at time of surgery were similar (27.8 years versus 27.7 years, p=0.85; 16.2 weeks in laparoscopy versus 15.4 weeks, p=0.59). Mass size was larger in those undergoing laparotomy (mean 8.8 cm versus 7.8 cm, p=0.03). The most common pathology was dermoid cyst (36%) and the risk of discovering a malignant tumor was 1%. Laparoscopy was not associated with a statistically increased risk of spontaneous abortion (SAB) or preterm delivery (PTD) (OR 1.53 [0.67, 3.52], p=0.31 and OR 0.95 [0.47, 1.89], p=0.88, respectively). The mean length of stay (LOS) was 2.5 days following laparoscopy versus 5.3 days following laparotomy (p<0.001). The decrease in EBL in laparoscopy was not statistically significant (94.0 mL in laparotomy versus 54.0 mL in laparoscopy, p=0.06). Operative time was similar in laparoscopy and laparotomy (80.0 min versus 72.5 min, p=0.09). Elective surgery was associated with a decreased risk of PTD (OR 0.13 [0.04, 0.48], p=0.05). Noncomparative studies were identified for laparoscopy and laparotomy. Laparotomy had more SAB and PTD than laparoscopy (pooled proportion = 0.02 versus 0.07, and pooled proportion = 0.02 versus 0.14, respectively). CONCLUSION: Laparoscopy for the surgical management of adnexal masses in pregnancy is associated with shorter LOS and similar risk of SAB or PTD. Elective surgery is associated with a decreased risk of PTD.

14.
J Am Chem Soc ; 143(4): 2016-2024, 2021 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-33471998

RESUMO

Stimuli-responsive structural transformations between discrete coordination supramolecular architectures not only are essential to construct smart functional materials but also provide a versatile molecular-level platform to mimic the biological transformation process. We report here the controlled self-assembly of three topologically unprecedented conjoined twin-cages, i.e., one stapled interlocked Pd12L6 cage (2) and two helically isomeric Pd6L3 cages (3 and 4) made from the same cis-blocked palladium corners and a new bis-bidentate ligand (1). While cage 2 features three mechanically coupled cavities, cages 3 and 4 are topologically isomeric helicate-based twin-cages based on the same metal/ligand stoichiometry. Sole formation of cage 2 or a dynamic mixture of cages 3 and 4 can be controlled by changing the solvents employed during the self-assembly. Structural conversions between cages 3 and 4 can be triggered by changes in both temperature/solvent and induced-fit guest encapsulations. Well-controlled interconversion between such topologically complex superstructures may lay a solid foundation for achieving a variety of functions within a switchable system.

15.
Environ Pollut ; 271: 116373, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33418288

RESUMO

The odor problems in river-type micro-polluted water matrixes are complicated compared to those in lakes and reservoirs. For example, the TY River in Jiangsu Province has been associated with complex odors, whereas the specific odor compounds were not clear. In this paper, a comprehensive study on characterizing the odors and odorants in source water from the TY River was conducted. Six odor types, including earthy, marshy, fishy, woody, medicinal, and chemical odors, were detected for the first time; correspondingly, thirty-three odor-causing compounds were identified. By means of evaluating odor activity values and reconstituting the identified odorants, 95, 93, 92, 90, 89 and 88% of the earthy, marshy, fishy, woody, medicinal and chemical odors in the source waters could be clarified. Geosmin and 2-methylisoborneol were associated with earthy odor, while amyl sulfide, dibutyl sulfide, propyl sulfide, dimethyl disulfide, dimethyl trisulfide and indole were related to marshy odor. The major woody and fishy odor compounds were vanillin, geraniol, ß-cyclocitral and 2,4-decadienal, 2-octenal, respectively. Medicinal and chemical odors were mainly caused by 2-chlorophenol, 4-bromophenol, 2,6-dichlorophenol and naphthalene, and 1,4-dichlorobenzene, respectively. This is the first study in which six odor types and thirty-three odorants were identified simultaneously in a river-type micro-polluted water source, which can offer a reference for odor management in drinking water treatment plants.


Assuntos
Odorantes , Purificação da Água , Animais , Rios , Água , Poluição da Água
16.
BMC Infect Dis ; 21(1): 62, 2021 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-33435894

RESUMO

BACKGROUND: Although traditional diagnostic techniques of infection are mature and price favorable at present, most of them are time-consuming and with a low positivity. Metagenomic next⁃generation sequencing (mNGS) was studied widely because of identification and typing of all pathogens not rely on culture and retrieving all DNA without bias. Based on this background, we aim to detect the difference between mNGS and traditional culture method, and to explore the relationship between mNGS results and the severity, prognosis of infectious patients. METHODS: 109 adult patients were enrolled in our study in Shanghai Tenth People's Hospital from October 2018 to December 2019. The diagnostic results, negative predictive values, positive predictive values, false positive rate, false negative rate, pathogen and sample types were analyzed by using both traditional culture and mNGS methods. Then, the samples and clinical information of 93 patients in the infected group (ID) were collected. According to whether mNGS detected pathogens, the patients in ID group were divided into the positive group of 67 cases and the negative group of 26 cases. Peripheral blood leukocytes, C-reactive protein (CRP), procalcitonin (PCT) and neutrophil counts were measured, and the concentrations of IL-2, IL-4, IL-6, TNF-α, IL-17A, IL-10 and INF-γ in the serum were determined by ELISA. The correlation between the positive detection of pathogens by mNGS and the severity of illness, hospitalization days, and mortality were analyzed. RESULTS: 109 samples were assigned into infected group (ID, 92/109, 84.4%), non-infected group (NID, 16/109, 14.7%), and unknown group (1/109, 0.9%). Blood was the most abundant type of samples with 37 cases, followed by bronchoalveolar lavage fluid in 36 cases, tissue, sputum, pleural effusion, cerebrospinal fluid (CSF), pus, bone marrow and nasal swab. In the ID group, the majority of patients were diagnosed with lower respiratory system infections (73/109, 67%), followed by bloodstream infections, pleural effusion and central nervous system infections. The sensitivity of mNGS was significantly higher than that of culture method (67.4% vs 23.6%; P < 0.001), especially in sample types of bronchoalveolar lavage fluid (P = 0.002), blood (P < 0.001) and sputum (P = 0.037), while the specificity of mNGS was not significantly different from culture method (68.8% vs 81.3%; P = 0.41). The number of hospitals stays and 28-day-motality in the positive mNGS group were significantly higher than those in the negative group, and the difference was statistically significant (P < 0.05). Age was significant in multivariate logistic analyses of positive results of mNGS. CONCLUSIONS: The study found that mNGS had a higher sensitivity than the traditional method, especially in blood, bronchoalveolar lavage fluid and sputum samples. And positive mNGS group had a higher hospital stay, 28-day-mortality, which means the positive of pathogen nucleic acid sequences detection may be a potential high-risk factor for poor prognosis of adult patients and has significant clinical value. MNGS should be used more in early pathogen diagnosis in the future.


Assuntos
Doenças Transmissíveis/diagnóstico , Testes Diagnósticos de Rotina/métodos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Metagenômica/métodos , Índice de Gravidade de Doença , Adulto , Idoso , Idoso de 80 Anos ou mais , Hemocultura/métodos , Líquido da Lavagem Broncoalveolar/microbiologia , China , Doenças Transmissíveis/mortalidade , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Sensibilidade e Especificidade , Escarro/microbiologia
17.
Free Radic Res ; : 1-11, 2021 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-33455488

RESUMO

Cardiovascular disease (CVD), including heart attack, stroke, heart failure, arrhythmia, and other congenital heart diseases remain the leading cause of morbidity and mortality worldwide. The leading cause of deaths in CVD is attributed to myocardial infarction due to the rupture of atherosclerotic plaque. Atherosclerosis refers a condition when restricted or even blockage of blood flow occurs due to the narrowing of blood vessels as a result of the buildup of plaques composed of oxidized lipids. It is well-established that free radical oxidation of polyunsaturated fatty acids (PUFAs) in lipoproteins or cell membranes, termed lipid peroxidation (LPO), plays a significant role in atherosclerosis. LPO products are involved in immune responses and cell deaths in this process, in which previous evidence supports the role of programmed cell death (apoptosis) and necrosis. Ferroptosis is a newly identified form of regulated cell death characterized by the iron-dependent accumulation of lipid hydroperoxides to lethal levels, which exhibits distinct features from apoptosis, necrosis and autophagy in morphology, biochemistry and genetics. Emerging evidence appears to demonstrate that ferroptosis is also involved in CVD. In this review, we summarize the recent progress on ferroptosis in CVD and atherosclerosis, highlighting the role of free radical LPO. The evidence underlying the ferroptosis and challenges in the field will also be critically discussed.

18.
J Affect Disord ; 282: 662-668, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33445089

RESUMO

Identifying cognitive dysfunction in the early stages of Bipolar Disorder (BD) can allow for early intervention. Previous studies have shown a strong correlation between cognitive dysfunction and number of manic episodes. The objective of this study was to apply machine learning (ML) techniques on a battery of cognitive tests to identify first-episode BD patients (FE-BD). Two cohorts of participants were used for this study. Cohort #1 included 74 chronic BD patients (CHR-BD) and 53 healthy controls (HC), while the Cohort #2 included 37 FE-BD and 18 age- and sex-matched HC. Cognitive functioning was assessed using the Cambridge Neuropsychological Test Automated Battery (CANTAB). The tests examined domains of visual processing, spatial memory, attention and executive function. We trained an ML model to distinguish between chronic BD patients (CHR-BD) and HC at the individual level. We used linear Support Vector Machines (SVM) and were able to identify individual CHR-BD patients at 77% accuracy. We then applied the model to Cohort #2 (FE-BD patients) and achieved an accuracy of 76% (AUC = 0.77). These results reveal that cognitive impairments may appear in early stages of BD and persist into later stages. This suggests that the same deficits may exist for both CHR-BD and FE-BD. These cognitive deficits may serve as markers for early BD. Our study provides a tool that these early markers can be used for detection of BD.

19.
Stem Cell Res Ther ; 12(1): 35, 2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33413674

RESUMO

BACKGROUND AND AIM: Periodontitis is a chronic inflammatory disease inducing the absorption of alveolar bone and leading to tooth loss. Human amnion-derived mesenchymal stem cells (HAMSCs) have been used for studying inflammatory processes. This study aimed to explore the role of long noncoding RNA (lncRNA) antisense noncoding RNA in the INK4 locus (ANRIL) in HAMSC-driven osteogenesis in lipopolysaccharide (LPS)-induced human bone marrow mesenchymal stem cells (HBMSCs). METHODS: The cells were incubated with a co-culture system. Reactive oxygen species (ROS) level and superoxide dismutase (SOD) activity were used to detect the oxidative stress level. Flow cytometry was performed to determine cell proliferation. The alkaline phosphatase (ALP) activity, Alizarin red assay, cell transfection, and rat mandibular defect model were used to evaluate the osteogenic differentiation. Quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR), Western blot analysis, dual-luciferase reporter assay, and immunofluorescence staining were used to evaluate the molecular mechanisms. RESULTS: This study showed that HAMSCs promoted the osteogenesis of LPS-induced HBMSCs, while the ANRIL level in HBMSCs decreased during co-culture. ANRIL had no significant influence on the proliferation of LPS-induced HBMSCs. However, its overexpression inhibited the HAMSC-driven osteogenesis in vivo and in vitro, whereas its knockdown reversed these effects. Mechanistically, this study found that downregulating ANRIL led to the overexpression of microRNA-125a (miR-125a), and further contributed to the competitive binding of miR-125a and adenomatous polyposis coli (APC), thus significantly activating the Wnt/ß-catenin pathway. CONCLUSION: The study indicated that HAMSCs promoted the osteogenic differentiation of LPS-induced HBMSCs via the ANRIL/miR-125a/APC axis, and offered a novel approach for periodontitis therapy.

20.
J Agric Food Chem ; 69(1): 7-27, 2021 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-33397106

RESUMO

As the most widely consumed fruit in the world, apple (Malus domestica Borkh.) fruits provide a high level of phenolics and have many beneficial effects on human health. The composition and content of phenolic compounds in natural apples differs according to the tissue types and cultivar varieties. The bioavailability of apple-derived phenolics, depending on the absorption and metabolism of phenolics during digestion, is the key determinant of their positive biological effects. Meanwhile, various processing technologies affect the composition and content of phenolic compounds in apple products, further affecting the bioavailability of apple phenolics. This review summarizes current understanding on the compositions, distribution, absorption, and metabolism of phenolic compounds in apple and their stability when subjected to common technologies during processing. We intend to provide an updated overview on apple phenolics and also suggest some perspectives for future research of apple phenolics.

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