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1.
Syst Rev ; 10(1): 56, 2021 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-33583421

RESUMO

BACKGROUND: High tibial osteotomy (HTO) has been used for over 60 years in clinical practice and mainly comprises two major techniques: closed wedge high tibial osteotomy (CWHTO) and open wedge high tibial osteotomy (OWHTO). However, these have been gradually replaced by total knee arthroplasty (TKA), due to inconsistent clinical results and many complications. With the concept of knee-protection and ladder treatment of osteoarthritis, as an effective minimally invasive treatment for knee osteoarthritis, HTO has once again received attention. METHODS: A systematic literature search was conducted in PubMed, Embase, ClinicalKey, CNKI, and the China Wanfang database. The search terms relating to osteoarthritis and high tibial osteotomy were used. Studies were considered eligible if the participants were adults with knee osteoarthritis (KOA) who had undergone HTO. A total of two reviewers participated in the selection of the studies. Reviewer 1 was assigned to screen titles and abstracts, and reviewer 2 to screen full-text data. Data extraction was completed by reviewer 2, and 30% were checked by the research team. Potential conflicts were resolved through discussion. The methodological quality was assessed using a risk of bias, based on the Cochrane handbook and Newcastle-Ottawa assessment scale. The outcome indicators are (1) posterior slope of tibial plateau, (2) the height of the patella, (3) fracture in the osteotomy plane, (4) survival rate, (5) special surgery knee score (HSS), and (6) the recurrence of varus deformity of the included studies were evaluated according to the guidelines of the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) working group (Atkins et al., BMJ 328:1490, 2004). RESULTS: Among the 18 articles included, 10 were prospective cohort studies, five were randomized controlled trial (RCT) studies, one was prospective comparative study (PCS), one was retrospective comparative study (RCS), and one was retrospective cohort. The earliest publication year was 1999, and the most recent was 2018. A total of 6555 eligible cases were included, comprised of 3351 OWHTO patients and 3204 CWHTO patients. Five RCT were assessed using risk of bias, based on the Cochrane handbook. Eleven cohort studies and two case-control studies were assessed using the Newcastle-Ottawa assessment scale. These six outcome indicators for a total of twenty-four evidence individuals were evaluated separately, among which the GRADE classification of 1, 2, and 6 was medium quality, and 3, 4, and 5 were low quality. Based on our systematic review, regardless of whether the chosen procedure was OWHTO or CWHTO, both HSS scores increased significantly as compared with the preoperative scores. Compared with CWHTO, the height of the patella and tibial posterior slope angle increased following OWHTO. Additionally, OWHTO has a better long-term survival rate and lower fracture rate, supporting OWHTO as the first treatment choice. CONCLUSIONS: For young patients with knee osteoarthritis (KOA), high tibial osteotomy (HTO) can be considered as a treatment option to replace total knee arthroplasty (TKA) to reduce the economic burden and promote the reasonable allocation of medical resources. This study shows that compared with CWHTO, OWHTO has certain advantages in long-term survival rate and lower fracture rate, but the level of evidence is lower. In the future, we will need larger sample sizes and longer follow-up randomized controlled trials to improve our research.

2.
Carbohydr Polym ; 258: 117684, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33593557

RESUMO

To control the release of nerve growth factor (NGF) in the injured peripheral nerve, NGF-loaded chitosan/PLGA composite microspheres ionically cross-linked by tripolyphosphate (TPP/Chitosan/PLGA-NGF) were prepared. The encapsulation efficiency of NGF ranged from 83.4 ± 1.5 % to 72.1 ± 1.6 % with TPP concentrations from 1 % to 10 %. Zeta potential and FT-IR analyses together with confocal microscopy demonstrated that multiple NGF-loaded PLGA microspheres were embedded in chitosan matrix, the mean size of TPP/Chitosan/PLGA-NGF microspheres ranged from 40.2 ± 3.4 to 49.3 ± 3.1 µm. The increase of TPP concentration improved the network stability and decreased the swelling ratio, resulting in the decreased NGF release from 67.7 ± 1.2 % to 45.7 ± 0.8 % in 49 days. The sustained release of NGF could promote PC12 cells differentiation and neurite growth in vitro. Moreover, in comparison with NGF solution without microencapsulation, TPP/Chitosan/PLGA-NGF microspheres enhanced sciatic nerve regeneration and prevented gastrocnemius muscle atrophy in rats. These results demonstrate the feasibility of using TPP/Chitosan/PLGA-NGF microspheres for neural tissue repair.

3.
J Virol ; 2021 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-33504601

RESUMO

We previously reported that human cytomegalovirus (HCMV) utilizes the cellular protein WD repeat-containing protein 5 (WDR5) to facilitate capsid nuclear egress. Here, we further show that HCMV infection results in WDR5 localization in a juxtanuclear region, and that its localization to this cellular site is associated with viral replication and late viral gene expression. Furthermore, WDR5 accumulated in the virion assembly compartment (vAC) and co-localized with vAC markers of gamma-tubulin (γ-tubulin), early endosomes, and viral vAC marker proteins pp65, pp28, and glycoprotein B (gB). WDR5 co-immunoprecipitated with multiple virion proteins, including MCP, pp150, pp65, pIRS1, and pTRS1, which may explain WDR5 accumulation in the vAC during infection. WDR5 fractionated with virions either in the presence or absence of Triton X-100 and was present in purified viral particles, suggesting that WDR5 was incorporated into HCMV virions. Thus, WDR5 localized to the vAC and was incorporated into virions, raising the possibility that in addition to capsid nuclear egress, WDR5 could also participate in cytoplasmic HCMV virion morphogenesis.Importance Human cytomegalovirus (HCMV) has a large (∼235-kb) genome that contains over 170 ORFs and exploits numerous cellular factors to facilitate its replication. In the late phase of HCMV infection cytoplasmic membranes are reorganized to establish the virion assembly compartment (vAC), which has been shown to necessary for efficient assembly of progeny virions. We previously reported that WDR5 facilitates HCMV nuclear egress. Here, we show that WDR5 is localized to the vAC and incorporated into virions, perhaps contributing to efficient virion maturation. Thus, findings in this study identified a potential role for WDR5 in HCMV assembly in the cytoplasmic phase of virion morphogenesis.

4.
Eur J Radiol ; 135: 109487, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33418383

RESUMO

PURPOSE: This study compares the image and diagnostic qualities of a DEep Learning Trained Algorithm (DELTA) for half-dose contrast-enhanced liver computed tomography (CT) with those of a commercial hybrid iterative reconstruction (HIR) method used for standard-dose CT (SDCT). METHODS: This study enrolled 207 adults, and they were divided into two groups: SDCT and low-dose CT (LDCT). SDCT was reconstructed using the HIR method (SDCTHIR), and LDCT was reconstructed using both the HIR method (LDCTHIR) and DELTA (LDCTDL). Noise, Hounsfield unit (HU) values, signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were compared between three image series. Two radiologists assessed the noise, artefacts, overall image quality, visualisation of critical anatomical structures and lesion detection, characterisation and visualisation. RESULTS: The mean effective doses were 5.64 ±â€¯1.96 mSv for SDCT and 2.87 ±â€¯0.87 mSv for LDCT. The noise of LDCTDL was significantly lower than that of SDCTHIR and LDCTHIR. The SNR and CNR of LDCTDL were significantly higher than those of the other two groups. The overall image quality, visualisation of anatomical structures and lesion visualisation between LDCTDL and SDCTHIR were not significantly different. For lesion detection, the sensitivities and specificities of SDCTHIR vs. LDCTDL were 81.9 % vs. 83.7 % and 89.1 % vs. 86.3 %, respectively, on a per-patient basis. SDCTHIR showed 75.4 % sensitivity and 82.6 % specificity for lesion characterisation on a per-patient basis, whereas LDCTDL showed 73.5 % sensitivity and 82.4 % specificity. CONCLUSIONS: LDCT with DELTA had approximately 49 % dose reduction compared with SDCT with HIR while maintaining image quality on contrast-enhanced liver CT.

5.
Nat Commun ; 12(1): 685, 2021 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-33514704

RESUMO

Tanshinones are the bioactive nor-diterpenoid constituents of the Chinese medicinal herb Danshen (Salvia miltiorrhiza). These groups of chemicals have the characteristic furan D-ring, which differentiates them from the phenolic abietane-type diterpenoids frequently found in the Lamiaceae family. However, how the 14,16-epoxy is formed has not been elucidated. Here, we report an improved genome assembly of Danshen using a highly homozygous genotype. We identify a cytochrome P450 (CYP71D) tandem gene array through gene expansion analysis. We show that CYP71D373 and CYP71D375 catalyze hydroxylation at carbon-16 (C16) and 14,16-ether (hetero)cyclization to form the D-ring, whereas CYP71D411 catalyzes upstream hydroxylation at C20. In addition, we discover a large biosynthetic gene cluster associated with tanshinone production. Collinearity analysis indicates a more specific origin of tanshinones in Salvia genus. It illustrates the evolutionary origin of abietane-type diterpenoids and those with a furan D-ring in Lamiaceae.


Assuntos
Abietanos/biossíntese , Sistema Enzimático do Citocromo P-450/genética , Evolução Molecular , Proteínas de Plantas/genética , Salvia miltiorrhiza/enzimologia , Abietanos/química , Ciclização , Sistema Enzimático do Citocromo P-450/metabolismo , Medicamentos de Ervas Chinesas/química , Genes de Plantas/genética , Genoma de Planta , Família Multigênica/genética , Proteínas de Plantas/metabolismo , Raízes de Plantas/química , Raízes de Plantas/metabolismo , Salvia miltiorrhiza/química , Salvia miltiorrhiza/genética
6.
ESC Heart Fail ; 8(1): 644-651, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33336560

RESUMO

AIMS: Many studies have explored the clinical characteristics of patients with coronavirus disease (COVID-19), especially patients with cardiovascular disease. However, associated mechanisms and markers remain to be further investigated. This study aimed to investigate the effect of α-hydroxybutyrate dehydrogenase (α-HBDH) levels on disease progression and prognosis of patients with COVID-19. METHODS AND RESULTS: One thousand seven hundred and fifty-one patients from the Leishenshan hospital in Wuhan were divided into elevated and normal groups by α-HBDH level, and the clinical information between the two groups was compared retrospectively. The main outcome evaluation criteria included in-hospital death and disease severity. Univariate and multivariate regression analyses, survival curves, logistic regression, and receiver operating characteristic curve models were performed to explore the relationship between elevated α-HBDH and the two outcomes. Besides, curve fitting analyses were conducted to analyse the relationship between computed tomography score and survival. Among 1751 patients with confirmed COVID-19, 15 patients (0.87%) died. The mean (SD) age of patients was 58 years in normal α-HBDH group and 66 years in elevated α-HBDH group (P < 0.001). The mortality during hospitalization was 0.26% (4 of 1559) for patients with normal α-HBDH levels and 5.73% (11 of 192) for those with elevated α-HBDH levels (P < 0.001). Multivariate Cox analysis confirmed an association between elevated α-HBDH levels and higher risk of in-hospital mortality [hazard ratio: 4.411, 95% confidence interval (95% CI), 1.127-17.260; P = 0.033]. Multivariate logistic regression for disease severity and α-HBDH levels showed significant difference between both groups (odds ratio = 3.759; 95% CI, 1.895-7.455; P < 0.001). Kaplan-Meier curves also illustrated the survival difference between normal and elevated α-HBDH patients (P < 0.001). CONCLUSIONS: Our study found that serum α-HBDH is an independent risk factor for in-hospital mortality and disease severity among COVID-19 patients. α-HBDH assessment may aid clinicians in identifying high-risk individuals among COVID-19 patients.

7.
J Endocrinol ; 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33295883

RESUMO

Polycystic ovarian syndrome (PCOS) is a major severe ovary disorder affecting 5-10% of reproductive women around the world. PCOS can be considered a metabolic disease because it is often accompanied by obesity and diabetes. Brown adipose tissue (BAT) contains abundant mitochondria and adipokines and has been proven to be effective for treating various metabolic diseases. Recently, allotransplanted BAT successfully recovered the ovarian function of PCOS rat. However, BAT allotransplantation could not be applied to human PCOS; the most potent BAT is from infants, so voluntary donors are almost inaccessible. We recently reported that single BAT xenotransplantation significantly prolonged the fertility of aging mice and did not cause obvious immunorejection. However, PCOS individuals have distinct physiologies from aging mice; thus, it remains essential to study whether xenotransplanted rat BAT can be used for treating PCOS mice. In this study, rat-to-mouse BAT xenotransplantation fortunately did not cause severe rejection reaction, and significantly recovered ovarian functions, indicated by the recovery of fertility, oocyte quality, and the levels of multiple essential genes and kinases. Besides, the blood biochemical index, glucose resistance, and insulin resistance were improved. Moreover, transcriptome analysis showed that the recovered PCOS F0 mother following BAT xenotransplantation could also benefit the F1 generation. Finally, BAT xenotransplantation corrected characteristic gene expression abnormalities found in the ovaries of human PCOS patients. These findings suggest that BAT xenotransplantation could be a novel therapeutic strategy for treating PCOS patients.

8.
J Endocrinol ; 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33258802

RESUMO

Glucagon-like peptide 1 (GLP-1) is an insulinotropic hormone and plays an important role in regulating glucose homeostasis. GLP-1 has a short half-life (t1/2<2 min) due to degrading enzyme dipeptidyl peptidase-IV and rapid kidney clearance, which limits its clinical application as a therapeutic reagent. We demonstrated recently that supaglutide, a novel GLP-1 mimetic generated by recombinant fusion protein techniques, exerted hypoglycemic and beta cell trophic effects in type 2 diabetes db/db mice. In the present study, we examined supaglutide's therapeutic efficacy and pharmacokinetics in diabetic rhesus monkeys. We found that a single subcutaneous injection of supaglutide of tested doses transiently and significantly reduced blood glucose levels in a dose-dependent fashion in the diabetic monkeys. During a 4-weeks intervention period, treatment of supaglutide of weekly dosing dose-dependently decreased fasting and random blood glucose levels. This was associated with significantly declined plasma fructosamine levels. The repeated administration of supaglutide remarkably also decreased body weight in a dose-dependent fashion accompanied by decreased food intake. Intravenous glucose tolerance test results showed that supaglutide improved glucose tolerance. The intervention also showed enhanced glucose-stimulated insulin secretion and improved lipid profile in diabetic rhesus monkeys. These results reveal that supaglutide exerts beneficial effects in regulating blood glucose and lipid homeostasis in diabetic rhesus monkeys.

9.
Neurosci Bull ; 2020 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-33367996

RESUMO

Anterograde viral tracers are powerful and essential tools for dissecting the output targets of a brain region of interest. They have been developed from herpes simplex virus 1 (HSV-1) strain H129 (H129), and have been successfully applied to map diverse neural circuits. Initially, the anterograde polysynaptic tracer H129-G4 was used by many groups. We then developed the first monosynaptic tracer, H129-dTK-tdT, which was highly successful, yet improvements are needed. Now, by inserting another tdTomato expression cassette into the H129-dTK-tdT genome, we have created H129-dTK-T2, an updated version of H129-dTK-tdT that has improved labeling intensity. To help scientists produce and apply our H129-derived viral tracers, here we provide the protocol describing our detailed and standardized procedures. Commonly-encountered technical problems and their solutions are also discussed in detail. Broadly, the dissemination of this protocol will greatly support scientists to apply these viral tracers on a large scale.

10.
Sci Rep ; 10(1): 22125, 2020 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-33335163

RESUMO

Biomarker selection and cancer classification play an important role in knowledge discovery using genomic data. Successful identification of gene biomarkers and biological pathways can significantly improve the accuracy of diagnosis and help machine learning models have better performance on classification of different types of cancer. In this paper, we proposed a LogSum + L2 penalized logistic regression model, and furthermore used a coordinate decent algorithm to solve it. The results of simulations and real experiments indicate that the proposed method is highly competitive among several state-of-the-art methods. Our proposed model achieves the excellent performance in group feature selection and classification problems.

12.
J Neurosci Methods ; 350: 109021, 2020 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-33316318

RESUMO

Cell tracking is a useful technique to monitor specific cell populations for their morphology, development, proliferation, migration, interaction, function, and other properties, both in vitro and in vivo. Using different materials and methodologies to label the target cells directly or indirectly, the dynamic biological processes in living organisms can be visualized with appropriate detection techniques. Viruses, with the unique ability to deliver exogenous genes into host cells, have been used as vectors to mediate gene transfer. Genetic labeling of target cells by viral vectors endows the cells to express reporter genes with high efficiency and specificity. In conjunction with corresponding imaging techniques, cells labeled with different genetic reporters mediated by different viral vectors can be monitored across spatial and temporal scales to fulfill various purposes and address different questions. In the present review, we introduce the basic principle of viral vectors in cell tracking and highlight the examples of cell tracking in various research areas.

13.
Gland Surg ; 9(5): 1244-1257, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33224799

RESUMO

Background: The incidence of thyroid cancer among young adults is increasing; however, the clinical challenges specific to this population, such as diagnosis, reduced healthcare access, and inconsistent care, have received limited attention. Here, we conducted a subgroup analysis on a series of relatively young patients with differentiated thyroid carcinomas (DTCs), focusing on those with distant metastases at stage II, to obtain a deeper understanding of the factors influencing survival. Methods: Information on <45- or <55-year-old patients at any T/N stage with distant metastasis (M1) was extracted from the SEER database according to the staging system in the 6th and 8th American Joint Committee on Cancer (AJCC) editions, respectively. Patient mortality was evaluated using Cox proportional hazards regression analyses and Kaplan-Meier analyses with log-rank tests. Results: Both cancer-specific and all-cause mortality rates per 1,000 person-years for patients ≥35 years old significantly differed from those of patients <35 years old. DTC-specific survival curves also significantly differed between these age groups, according to both the AJCC 6.0 and 8.0-based analyses (P=0.0017 and P<0.001, respectively), as did patient survival curves (P=0.0003, P<0.001, respectively). The multivariate Cox regression model also revealed that poor OS was strongly predicted by race (P<0.001) in the analysis based on the criteria of 8th AJCC staging system. Conclusions: Age is a risk factor for disease-specific and overall survival (OS) in young patients with stage II DTC, and young male patients exhibited poorer survival than females. Race also emerged as a potential risk factor for young patients in stage II. These findings offer guidance for improving the older and newer versions of the AJCC staging system.

14.
J Agric Food Chem ; 2020 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-33206517

RESUMO

Caffeine (Cf) is one of the important components of plant-derived drinks, such as tea, coffee, and cola. It can protect soft tissues from being infected by pathogens and is also medically beneficial for human health. In this review, we first introduced the Cf biosynthesis pathways in plants and the related N-methyltransferases (NMTs), with a focus on the current research status of the substrate specificity, structural basis for substrate recognition, and catalytic mechanism in members of the caffeine synthase gene family. In addition, we addressed the expression characteristics and potential regulatory mechanisms of NMTs and also projected the future research directions. The goal was to summarize the Cf biosynthetic pathway and related NMTs in plants and to provide the molecular basis for regulating the caffeine biosynthesis, so as to effectively guide future tea and coffee breeding.

15.
Medicine (Baltimore) ; 99(48): e23409, 2020 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-33235120

RESUMO

BACKGROUND: Talaromyces marneffei (T marneffei), known as a significant pathogen in patients with AIDS in Southeast Asia, is a dimorphic fungus, which can cause deadly systematic infection in immunocompromised hosts. What is more, the dimorphic phase transition has been reported as a conspicuous process linked with virulence. Interestingly, the yeast form was found in infected individuals, representing the pathogenic phase. However, few researches were found to study the mechanism of dimorphic transition. Thus, a diverse insight into the dimorphic switch mechanism, is urgently needed and we are the first one to research the mechanism of dimorphism. METHODS: Firstly, we investigated the microarray of T. marneffei in the Gene Expression Omnibus database (GEO) for differentially expressed genes (DEGs). Then Database for Annotation, Visualization and Integrated Discovery (DAVID) v6.8 was employed to analyze the underlying enrichment and pathway in biological process of DEGs. Meanwhile, protein-protein interaction (PPI) network was constructed using STRING database. On the strength of the theory that similar amino acid sequences share similar structures, which play a decisive role on the function of protein, three dimensional structures of hub-genes were predicted to further investigate the likely function of hub-genes. RESULTS: GSE51109 was elected as the eligible series for the purpose of our research, including GSM1238923 (GSM23), GSM1238924 (GSM24), and GSM1238925 (GSM25). PMAA_012920, PMAA_028730, PMAA_068140, PMAA_092900, PMAA_032350 were the most remarkable genes in all of the three PPI networks, thus, were viewed as hub-genes. With regard to the three-dimensional construction, except that there was no significant prediction structure of PMAA_092900 with the criterion seq identify > 30%, GMQE: 0-1, QMEAN4: -4-0, the parallel templates for four structures were Crystal structure of Saccharomyces cerevesiae mitochondrial NADP(+)-dependent isocitrate dehydrogenase in complex with isocitrate, Organellar two-pore channels (TPCs), Yeast Isocitrate Dehydrogenase (Apo Form) and Crystal Structure Of ATP-Dependent Phosphoenolpyruvate Carboxykinase From Thermus thermophilus HB8 in order. CONCLUSION: The dimorphic transition of T. marneffei was viewed as a pathogenic factor and DEGs were observed. In-depth study of the function and pathway of DEGs revealed that PMAA_012920, PMAA_028730, PMAA_068140, PMAA_092900, PMAA_032350 were most likely acting as the hub-genes and were likely taking effect through regulating energy metabolism.

16.
Front Med (Lausanne) ; 7: 598870, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33240911

RESUMO

Objectives: The coronavirus disease (COVID-19) pandemic has caused a large number of deaths. Some patients with severe or critical COVID-19 have been observed to have elevated bilirubin levels. Studies on the association of bilirubin level and mortality in patients with COVID-19 are limited. This study aimed to examine the role of bilirubin levels in COVID-19 severity and mortality. Methods: A retrospective cohort study was conducted in patients hospitalized with COVID-19 in Leishenshan Hospital in Wuhan, China. Cox regression analyses and logistic regression analyses were conducted to investigate the risks for mortality and disease severity, respectively. Kaplan-Meier analyses with log-rank tests were performed to assess the association between bilirubin level and survival. Results: In total, 1,788 patients with COVID-19 were included in the analysis. 5.8% (4/69) of patients in the elevated serum total bilirubin (STB) group died, compared to 0.6% (11/1,719) of patients in the non-elevated STB group. The median alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities in the elevated STB group were 29 U/L [interquartile range (IQR): 16-45 U/L] and 22 U/L (IQR: 13-37 U /L), respectively, which were significantly higher than the median ALT (median: 23, IQR: 15-37) and AST (median: 20, IQR: 16-26) activities in the non-elevated STB group (both p < 0.05). Patients with an elevated STB level showed increased mortality [hazard ratio (HR): 9.45, P = 0.002], elevated conjugated bilirubin (CB) levels (HR: 4.38, P = 0.03), and an elevated ratio of CB to unconjugated bilirubin (UCB, CB/UCB) (HR: 2.49, P = 0.01). CB/UCB was positively correlated with disease severity (odds ratio: 2.21, P = 0.01). Conclusions: COVID-19 patients with elevated STB and CB levels had a higher mortality, and CB/UCB was predictive of disease severity and mortality. Thus, it is necessary to pay special attention to COVID-19 patients with elevated bilirubin levels in clinical management.

17.
Artigo em Inglês | MEDLINE | ID: mdl-33243711

RESUMO

Cinnamomum camphora (L.) Presl, rich in terpenoids, is an important commercial plant. The monoterpenes borneol and camphor are highly desired compounds that have been widely and diversely used in medicine and spices since ancient times. However, the key enzymes in the biosynthetic pathway of borneol and camphor in C. camphora remains unknown, which limits access to these natural products. Here, the chirality of borneol and camphor were identified in C. camphora leaves. Besides the main (+)-borneol and (+)-camphor, C. camphora also contains small amounts of (-)-borneol and (-)-camphor. Then, CcBDH3 - an efficient (+)-borneol dehydrogenase (BDH) - was identified that catalyzed (+)-borneol into (+)-camphor in the presence of NAD+. The Km value was 25.1 µM with a kcat value of 5.4 × 10-3 s-1 at pH 8.5 and 30 °C. CcBDH3, which also yields (-)-camphor from (-)-borneol as a substrate, had a Km value of 36.9 µM with a kcat of 2.1 × 10-3 s-1, and pH of 8.0 and temperature of 32 °C. We further compared the conformational specificity of two other reported BDHs, ZSD1 and ADH2, and found that ZSD1 had the highest conversion rate with (-)-borneol. These findings provide a new way for the production of camphor with various optical activities by metabolic engineering, and the identified camphor biosynthesis pathway provides the foundation for using genetic engineering to improve the production and purity of (+)-borneol in planta.

18.
J Int Med Res ; 48(10): 300060520962347, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33100092

RESUMO

OBJECTIVE: This study aimed to examine the relationship between total bilirubin levels and initial ischemic stroke in patients with non-valvular atrial fibrillation. METHODS: This was a retrospective study. Atrial fibrillation was diagnosed by 24-hour Holter electrocardiography and serum total bilirubin levels were divided into quintiles. Ischemic stroke was diagnosed by symptoms, signs, and a medical image examination. The multivariate Cox proportional hazards model and survival analysis were used to estimate the association of total bilirubin with initial ischemic stroke. RESULTS: We studied 316 patients with non-valvular atrial fibrillation. During follow-up, there were 42 (13.29%) first ischemic strokes. After multivariate adjustment, for each 1 µmol/L increase in total bilirubin, the risk of first ischemic stroke increased by 4% (95% confidence interval [CI]: 1.01, 1.07). When using the first quintile as the reference, from the second to fifth quintiles, the risks of first ischemic stroke were 0.52 (95% CI: 0.17, 1.65), 0.23 (95% CI: 0.06, 0.87), 0.92 (95% CI: 0.32, 2.67), and 1.33 (95% CI: 1.09, 4.41), respectively. The optimal cut-off point of total bilirubin for the lowest risk of ischemic stroke was 17.0 µmol/L. CONCLUSIONS: Total bilirubin levels are nonlinearly associated with initial ischemic stroke in patients with non-valvular atrial fibrillation.

19.
Infect Drug Resist ; 13: 3811-3816, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33122926

RESUMO

Purpose: Talaromyces marneffei is a highly invasive fungus, causing fatal mycosis in patients with or without HIV in Southeast and Eastern Asia. However, its presence in patients with systemic lupus erythematosus is rarely reported. Methods: We reported two SLE patients infected by T. marneffei and reviewed other patients reported in the English literature. All cases were pooled for analysis. Results: Eleven patients with SLE infected with T. marneffei infection were identified, including the two presented here. Three were male and eight were female; all were HIV negative. All the patients, except two where data were missing, had received immunosuppressants before T. marneffei infection. The main clinical features included fever, cough, lymph node enlargement, gastrointestinal symptoms, and rash. Five patients were misdiagnosed as having SLE exacerbation. T. marneffei was detected via culture or histopathologic analysis, with the fungus most commonly found in the blood. Seven of the 11 patients were successfully treated by timely antifungal therapy with concomitant SLE control, while four patients who did not receive antifungal therapy died. Conclusion: T. marneffei infection should be excluded when SLE patients, especially if on long-term immunosuppressants, present with fever, cough, lymph node enlargement, gastrointestinal symptoms, and rash. Controlling the lupus and timely antifungal treatment can improve the outcomes of SLE patients with T. marneffei infection.

20.
Int J Med Sci ; 17(16): 2468-2476, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33029089

RESUMO

Rationale: Coronavirus disease 2019 (COVID-19) was first announced in Wuhan, and has rapidly evolved into a pandemic. However, the risk factors associated with the severity and mortality of COVID-19 are yet to be described in detail. Methods: We retrospectively reviewed the information of 1525 cases from the Leishenshan Hospital in Wuhan. Univariate and multivariate Cox regression analyses were generated to explore the relationship between procalcitonin (PCT) level and the progression and prognosis of COVID-19. Univariate and multivariate logistic regression analyses were performed to explore the relationship between disease severity in hospitalized patients and their PCT levels. Survival curves and the cumulative hazard function for COVID-19 progression were conducted in the two groups. To further detect the relationship between the computed tomography score and survival days, curve-fitting analyses were performed. Results: Patients in the elevated PCT group had a higher incidence of severe and critical severity conditions (P < 0.001), death, and higher computed tomography (CT) scores. There was an association between elevated PCT levels and mortality in the univariate ((hazard ratio [1], 3.377; 95% confidence interval [2], 1.012-10.344; P = 0.033) and multivariate Cox regression analysis (HR, 4.933; 95% CI, 1.170-20.788; P = 0.030). Similarly, patients with elevated PCT were more likely to have critically severe disease conditions in the univariate (odds ratio [2], 7.247; 95% CI, 3.559-14.757; P < 0.001) and multivariate logistic regression analysis (OR, 10.679; 95% CI, 4.562-25.000; P < 0.001). Kaplan-Meier curves showed poorer prognosis for patients with elevated PCT (P = 0.024). The CT score 1 for patients with elevated PCT peaked at day 40 following the onset of symptoms then decreased gradually, while their total CT score was relatively stable. Conclusion: PCT level was shown as an independent risk factor of in-hospital mortality among COVID-19 patients. Compared with inpatients with normal PCT levels, inpatients with elevated PCT levels had a higher risk for overall mortality and critically severe disease. These findings may provide guidance for improving the prognosis of patients with critically severe COVID-19.


Assuntos
Betacoronavirus , Infecções por Coronavirus/etiologia , Infecções por Coronavirus/mortalidade , Pneumonia Viral/etiologia , Pneumonia Viral/mortalidade , Pró-Calcitonina/sangue , Idoso , Antibacterianos/uso terapêutico , Antivirais/uso terapêutico , Betacoronavirus/efeitos dos fármacos , China/epidemiologia , Comorbidade , Infecções por Coronavirus/diagnóstico por imagem , Infecções por Coronavirus/tratamento farmacológico , Progressão da Doença , Feminino , Hospitalização , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/diagnóstico por imagem , Prognóstico , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
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