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1.
Mol Med Rep ; 22(5): 4197-4206, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33000244

RESUMO

Axial spondyloarthritis (AxSpA) is a chronic rheumatic disease involving the axial skeleton. Recent evidence suggested that certain circular RNAs (circRNAs) have a crucial role in rheumatic diseases. However, the functions of circRNAs in AxSpA have remained largely elusive. The present study identified the utility of the circRNA Homo sapiens (hsa)_circ_0079787 as a potential biomarker for AxSpA. A total of 5 circRNAs (hsa_circ_0002715, hsa_circ_0001947, hsa_circ_0079787, hsa_circ_0000367 and hsa_circ_0035197) were determined in the peripheral blood of 46 patients with AxSpA, 46 patients with systemic lupus erythematosus (SLE) and 25 healthy controls (HC) by reverse transcription­quantitative PCR analysis. The detailed clinical history of each patient was recorded and the correlations between these circRNAs and clinical characteristics were analyzed. Furthermore, receiver operating characteristic (ROC) curves were constructed to evaluate the diagnostic value of hsa_circ_0079787 and other factors for AxSpA. Of the 5 selected circRNAs, the expression of hsa_circ_0079787 was indicated to be significantly reduced in the peripheral blood of patients with AxSpA as compared with the levels in HCs and patients with SLE. The peripheral blood levels of hsa_circ_0079787 in patients with AxSpA were negatively correlated with the Bath Ankylosing Spondylitis Disease Activity Index and positively correlated with the platelet count (PLT) and the lymphocyte­to­monocyte ratio. In addition, the expression of peripheral blood hsa_circ_0079787 in male patients with AxSpA was negatively correlated with the mean platelet volume (MPV) and positively correlated with the plateletcrit (PCT). ROC curve analysis suggested that hsa_circ_0079787 and the combination of hsa_circ_0079787­PLT­MPV­PCT had a significant diagnostic value for AxSpA. hsa_circ_0079787 and the combination of hsa_circ_0079787­PLT­MPV­PCT was also able to differentiate between patients with AxSpA and those with SLE. In conclusion, peripheral­blood hsa_circ_0079787 and the combination of hsa_circ_0079787­PLT­MPV­PCT may provide improved diagnostic accuracy for AxSpA. In addition, the levels of hsa_circ_0079787 in the peripheral blood were correlated with disease activity and severity of AxSpA.

2.
Medicine (Baltimore) ; 99(41): e22680, 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33031337

RESUMO

Multiple factors, including increasing incidence, poor knowledge of stroke and lack of effective, noninvasive and convenient stroke risk prediction tools, make it more difficult for precautions against stroke in China. Effective prediction models for stroke may assist to establish better risk awareness and management, healthier lifestyle, and lower stroke incidence for people.The China Health and Retirement Longitudinal Survey was the development cohort. Logistic regression was applied to model's development, in which the candidate variables with statistically significant coefficient were included in the prediction model. The area under receiver operating characteristic curve (AUC) and 10-times cross-validation were used for internal validation. Cutoff point of high-risk group was measured by Youden index. The China Health and Nutrition Survey was the validation cohort.The development cohort and the validation cohort included 16557 and 5065 participants, and the incidence density was 358.207/100,000 person-year and 350.701/100,000 person-year, respectively. The model for 2-year new-onset stroke risk prediction included age, hypertension, diabetes, heart disease, and smoking. The AUC and cross-validation AUC were 0.707 (95% confidence interval[CI]: 0.664, 0.750) and the 0.710 (95% CI: 0.650, 0.736). The sensitivity, specificity and accuracy of the cutoff point were 0.774, 0.545, and 0.319. The AUC and cross-validation AUC were 0.800 (95% CI: 0.744, 0.856) and 0.811(95% CI:0.714, 0.847), and the sensitivity, specificity and accuracy of cutoff point being 0.857,0.569, and 0.426 in external validation.A simple prediction tool using 5 noninvasive and easily accessible factors can assist in 2-year new-onset stroke risk prediction in Chinese people over 45 years old, which is believed to be applicable in identifying high-risk individuals and health management in China.

3.
J Infect Dis ; 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33031517

RESUMO

BACKGROUND: Cytomegalovirus (CMV) can cause congenital infection and is the leading cause of nongenetic newborn disabilities. V160, a conditionally replication-defective virus, is an investigational vaccine under evaluation for prevention of congenital CMV. The vaccine was well tolerated and induced both humoral and cellular immunity in CMV-seronegative trial participants [NCT10986010]. T-cell mediated immunity is important for immune control of CMV. Here we describe efforts to understand the quality attributes of the T-cell responses induced by vaccination. METHODS: Using multicolor flow cytometry, we analyzed vaccine-induced T-cells for memory phenotype, antigen specificity, cytokine profiles, and cytolytic potential. Moreover, antigen-specific T-cells were sorted from four participants and next generation sequencing was used to trace clonal lineage development during the course of vaccination using T-cell receptor ß-chain (TCRß) sequences as identifiers. RESULTS: The results demonstrated that vaccination elicited polyfunctional CD4 and CD8 T-cells to two dominant antigens, pp65 and IE1, with a predominantly effector phenotype. Analysis of TCR repertoires showed polyclonal expansion of pp65- and IE1-specific T-cells after vaccination. CONCLUSION: V160 induced a genetically diverse and polyfunctional T-cell response and the data support further clinical development of V160 for prevention of CMV infection and congenital transmission.

4.
Molecules ; 25(19)2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33019644

RESUMO

Ceratophyllum demersum L. (CDL) is a traditional Chinese herb to treat many diseases, but research on its anti-diabetic activity is not available. In this research, the α-glucosidase inhibitory ability and phytochemical constituents of CDL extract were firstly studied. Optimal ultrasound-assisted extraction conditions for α-glucosidase inhibitors (AGIs) were optimized by single factor experiment and response surface methodology (RSM), which was confirmed as 70% methanol, liquid-to-solid ratio of 43 (mL/g), extraction time of 54 min, ultrasonic power of 350 W, and extraction temperature of 40 °C. The lowest IC50 value for α-glucosidase inhibition was 0.15 mg dried material/mL (mg DM/mL), which was much lower than that of acarbose (IC50 value of 0.64 mg DM/mL). In total, 80 compounds including 8 organic acids, 11 phenolic acids, 25 flavonoids, 21 fatty acids, and 15 others were identified or tentatively identified from CDL extract by HPLC-QTOF-MS/MS analysis. The results suggested that CDL could be a potential source of α-glucosidase inhibitors. It can also provide useful phytochemical information for research into other bioactivities.

5.
Food Funct ; 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33026021

RESUMO

The effect of short-term intake of high- and low-concentrations of sucrose solution on the neurochemistry of male and female mice was studied. The body weight, feed intake, sucrose solution consumption and brain monoamine neurotransmitters were determined after 34 days' intake of 1% and 8% sucrose solutions. The gene expression and protein levels related to dopamine and opioids were also determined. The results showed that the intake of 1% and 8% sucrose solution for 34 days did not cause significant changes in the weight development of both male and female mice. The preference for sucrose varies with sex. Both males and females had greater preference for the high concentration sucrose solution than the low concentration sucrose solution. The continuous intake of sucrose stimulated the release of monoamine neurotransmitters (DA, 5-HT, NE) in the brains of mice, and the reward effect of 8% sucrose solution is significantly higher than that of 1% sucrose solution. The sex of mice did not affect the release of neurotransmitters. The gene expressions of D1 and D2 were up-regulated in the 1% sucrose group of male mice, while the OPRM1 gene expression was down-regulated. The expression of these three genes in the 8% sucrose group of male mice was all down-regulated, while the gene expressions of D1 and D2 in the 1% and 8% sucrose group (p < 0.05) of female mice were both up-regulated.

6.
Metabolomics ; 16(10): 110, 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33037443

RESUMO

INTRODUCTION: Epilepsy is a chronic disease, while epileptogenesis is a latent period where brain will be transformed into an epileptic one. Mechanisms of epileptogenesis remain unclear. OBJECTIVES: We aim to provide information of hippocampal lipidomic changes related with epileptogenesis in two kindling models. Combining hippocampal structural imaging indices, our study also attempts to assess biochemical alterations as a function of epileptogenesis in a non-invasive way. METHODS: We constructed two kinds of chemical kindling models, which have long been used as models of epileptogenesis. Two kindling and one control groups were all subjected to structural imaging acquisition after successfully kindled. Voxel-based morphometry, a postprocessing method for brain imaging data, was used to segment and extract hippocampal gray matter volume for subsequent integrative analysis. LC-MS based lipidomic analysis was applied to identify distinct hippocampal lipidomic profiles between kindling and control groups. Further, we regress hippocampal structural indices on lipids to identify those associated with both epileptogenesis and brain structural changes. RESULTS: We report distinct lipidomic profiles between kindling groups and control. A total of 638 lipids were detected in all three groups. Among them were 98 individual lipids, showing significant alterations, in particular lipid class of phosphatidylethanolamine (PE), glucosylceramide and phosphatidylcholine. Hippocampal gray matter volumes were found significant different between groups (P = 0.0223). After combining brain imaging data, we demonstrate several individual PE, namely PE(O-18:1_22:3), PE(O-18:1_22:6) and PE(18:1_18:1), are associated with both epileptogenesis and hippocampal gray matter volume. CONCLUSION: This study suggests metabolic pathway of PE might involve in epileptogenesis. Also, for the first time, we link level of PE with structural brain imaging indices, in an attempt to potentiate the futuristic application of noninvasive brain imaging techniques to identify epileptogenesis in its latent period.

7.
Curr Drug Metab ; 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33038908

RESUMO

BACKGROUND: With significant clinical effects, traditional Chinese medicine (TCM) has been attracting increasing interest of the world's scientific community. However, TCM contains immense amounts of chemical components. It is a great challenge to objectively evaluate of the correlation between the in vivo process and the therapeutic effect of TCM. The purpose of this systematic review was to summarize the recent investigation (from 2017 to 2019) on preclinical pharmacokinetics (PK) of TCM via liquid chromatography coupled with mass spectrometry (LC-MS/MS). METHOD: We reviewed the published articles regarding the PK of TCM by LC-MS/MS. In addition, we summarized information on PK parameter of bioactive components, single herb and traditional Chinese medicine prescriptions. RESULTS: The vast majority of literatures on preclinical PK of TCM use single oral administration, the biological matrix is mostly rat plasma, and the main PK parameters include AUC, Cmax, Tmax and T1/2, etc. Conclusion: Although LC-MS/MS can be used for high-throughput analysis, the characterization of in vivo processes of TCM is still has a long way. With the advantages of high sensitivity, high specificity and simple operation, the increasingly mature LC-MS/MS technology will play an important role in the PK of TCM.

8.
Artigo em Inglês | MEDLINE | ID: mdl-33043389

RESUMO

Several quorum sensing systems occurring in Bacillus subtilis, e.g. Rap-Phr systems, were reported to interact with major regulatory proteins, such as ComA, DegU, and Spo0A, in order to regulate competence, sporulation, and synthesis of secondary metabolites. In this study, we characterized a novel Rap-Phr system, RapA4-PhrA4, in Bacillus velezensis NAU-B3. We found that the rapA4 and phrA4 genes were co-transcribed in NAU-B3. When rapA4 was expressed in the heterologous host Bacillus subtilis OKB105, surfactin production and sporulation were severely inhibited. However, when the phrA4 was co-expressed, the RapA4 activity was inhibited. The transcription of the surfactin synthetase srfA gene and sporulation-related genes were also regulated by the RapA4-PhrA4 system. In vitro results obtained from electrophoretic mobility shift assay (EMSA) proved that RapA4 inhibits ComA binding to the promoter of the srfA operon, and the PhrA4 pentapeptide acts as anti-activator of RapA4. We also found that the F24 residue plays a key role in RapA4 function. This study indicated that the novel RapA4-PhrA4 system regulates the surfactin synthesis and sporulation via interaction with ComA, thereby supporting the bacterium to compete and to survive in a hostile environment. KEY POINTS: •Bacillus velezensis NAU-B3 has a novel Rap-Phr quorum sensing system, which does not occur in model strains Bacillus subtilis 168 and B. velezensis FZB42. •RapA4-PhrA4 regulates surfactin production and sporulation. •RapA4-PhrA4 interacts with the ComA protein from ComP/ComA two-component system.

9.
Nanotechnology ; 32(1): 015704, 2020 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-33043904

RESUMO

The biological responses of multidimensional carboxylated carbon-based nanomaterials (c-CBNs), including carboxylated graphene, carbon nanotube, and fullerene, on human lung A549 cells were investigated by using metabolomics technology. The structure and components of c-CBNs were characterized, and their biological effects were evaluated through cell apoptosis and viability analysis. Additionally, the metabolomics analysis of the nanomaterial-cell interaction system was performed using the established platform combining liquid chromatography-mass spectrometry (LC-MS) with the bioinformatics system. Results revealed that all tested c-CBNs demonstrated some biological effects in our cell model. However, significant metabolomic alterations induced by c-CBNs were also observed mainly in amino acids, organic acids, glycerophospholipids, and glycerolipids. Further, under the tested concentrations, the multiple dimensions of c-CBNs played a major role in determining the metabolic process in various interaction modes. This study provides an advanced alternative for evaluating metabolic effects of multidimensional nanomaterials through metabolomics technology considering the association between dimension and metabolic characteristics.

10.
Signal Transduct Target Ther ; 5(1): 227, 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33028824

RESUMO

Nicotinamide adenine dinucleotide (NAD+) and its metabolites function as critical regulators to maintain physiologic processes, enabling the plastic cells to adapt to environmental changes including nutrient perturbation, genotoxic factors, circadian disorder, infection, inflammation and xenobiotics. These effects are mainly achieved by the driving effect of NAD+ on metabolic pathways as enzyme cofactors transferring hydrogen in oxidation-reduction reactions. Besides, multiple NAD+-dependent enzymes are involved in physiology either by post-synthesis chemical modification of DNA, RNA and proteins, or releasing second messenger cyclic ADP-ribose (cADPR) and NAADP+. Prolonged disequilibrium of NAD+ metabolism disturbs the physiological functions, resulting in diseases including metabolic diseases, cancer, aging and neurodegeneration disorder. In this review, we summarize recent advances in our understanding of the molecular mechanisms of NAD+-regulated physiological responses to stresses, the contribution of NAD+ deficiency to various diseases via manipulating cellular communication networks and the potential new avenues for therapeutic intervention.

11.
Int J Cardiol ; 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33038407

RESUMO

PURPOSE: Our study aimed to comprehensively explore efficient prognostic indicators in idiopathic dilated cardiomyopathy (IDCM) patients with reduced left ventricular ejection fraction (LVEF<40%). BACKGROUND: Prognostic value of cardiac magnetic resonance(CMR) parameters for IDCM have been inconsistent. METHODS: 126 IDCM patients with reduced LVEF (<40%) were retrospectively enrolled. Cardiac function parameters, myocardial strain indices and myocardial fibrosis were evaluated. Laboratory data also were analyzed. The endpoint was a combination of major adverse cardiac events (MACEs), including cardiac death, heart transplantation, and rehospitalization. Prognostic value was evaluated by the Kaplan-Meier method and Cox regression. RESULTS: During a median follow-up of 31 months, 44 patients experienced MACEs, including 9 deaths, 1 heart transplantation, and 34 rehospitalizations due to heart failure. Univariate and multivariate Cox analyses showed that cardiac function and myocardial strain indexes were not associated with the prognosis of IDCM (all p > 0.05). NT-proBNP (HR 1.5, 95%CI: 1.053 to 2.137), Late­gadolinium enhancement(LGE) mass (HR 1.022, 95%CI: 1.005 to 1.038), and LGE mass/left ventricle mass were significant predictors (HR 1.027, 95%CI: 1.007 to 1.046) for MACEs, all p < 0.05. Besides, poorest prognosis was observed in IDCM patients with positive LGE combined with NT-proBNP (log-rank = 27.261, p ≤ 0.001). CONCLUSION: NT-proBNP and extent of LGE were reliable predictors in IDCM patients with reduced LVEF. Additionally, presence of LGE combined with NT-proBNP showed the strongest prognostic value in IDCM with reduced LVEF. Myocardial strain parameters seemed to have no prognostic value in IDCM patients with reduced LVEF.

13.
Free Radic Biol Med ; 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33059020

RESUMO

Metabolic reprogramme was a key characteristic of malignant tumors. Increased evidences indicated that besides Warburg effect (abnormal glucose metabolism), abnormal lipid metabolism played more and more important in progression and metastasis of malignant tumors. MiR-15a-5p could inhibit development of lung cancer, while its regulating mechanism, especially the role in lipid metabolism still remained unclear. In this study, we confirmed that miR-15a-5p inhibited proliferation, migration and invasion of lung cancer cells. The online analysis of Mirpath v.3 predicted that miR-15a-5p was closely associated with fatty acid synthesis and lipid metabolism. In vitro cell experiments revealed that miR-15a-5p significantly suppressed fatty acid synthesis of lung cancer cells by inhibiting acetate uptake. Extensive analysis indicated that miR-15a-5p could suppress acetyl-CoA activity and decrease histone H4 acetylation by inhibiting ACSS2 expression. In addition, we also observed that ACSS2 located in nucleus under hypoxic conditions, while miR-15a-5p could be transported into nucleus to inhibit the function of ACSS2. Our study unveiled a novel mechanism of miR-15a-5p in inhibiting metastasis of lung cancer cells by suppressing lipid metabolism via suppression of ACSS2 mediated acetyl-CoA activity and histone acetylation.

14.
Cancer Res ; 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33067266

RESUMO

Frontier evidence suggests that dysregulation of long non-coding RNAs (lncRNAs) is ubiquitous in all human tumors, indicating that lncRNAs might have essential roles in tumorigenesis. Therefore, an in-depth study of the roles of lncRNA in nasopharyngeal carcinoma (NPC) carcinogenesis might be helpful to provide novel therapeutic targets. Here we report that lncRNA TINCR was significantly upregulated in NPC and was associated positively with poor survival. Silencing TINCR inhibited NPC progression and cisplatin resistance. Mechanistically, TINCR bound ACLY and protected it from ubiquitin degradation to maintain total cellular acetyl-CoA levels. Accumulation of cellular acetyl-CoA promoted de novo lipid biosynthesis and histone H3K27 acetylation, which ultimately regulated the peptidyl arginine deiminase 1 (PADI1)-MAPK-MMP-2/9 pathway. In addition, IGF2BP3 interacted with TINCR and slowed its decay, which partially accounted for TINCR upregulation in NPC. These findings demonstrate that TINCR acts as a crucial driver of NPC progression and chemoresistance and highlights the newly identified TINCR-ACLY-PADI1-MAPK-MMP2/9 axis as a potential therapeutic target in NPC.

15.
Diabetes ; 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33067313

RESUMO

Diabetic kidney disease (DKD) remains the most common cause of kidney failure and the treatment options are insufficient. Here, we used a connectivity mapping approach to first collect 15 gene expression signatures from 11 DKD related published independent studies. Then, by querying the Library of Integrated Network-based Cellular Signatures (LINCS) L1000 dataset, we identified drugs and other bioactive small molecules that are predicted to reverse these gene signatures in the diabetic kidney. Among the top consensus candidates, we selected a PLK1 inhibitor (BI-2536) for further experimental validation. We found that PLK1 expression was increased in the glomeruli of both human and mouse diabetic kidneys and localized largely in mesangial cells. We also found that BI-2536 inhibited mesangial cell proliferation and extracellular matrix in-vitro and ameliorated proteinuria and kidney injury in DKD mice. Further pathway analysis of the genes predicted to be reversed by the PLK1 inhibitor were of members of the TNF-α/NF-κB, JAK/STAT, and TGF-ß/Smad3 pathways. In vitro, either BI-2536 treatment or knockdown of PLK1 dampened the NF-κB and Smad3 signal transduction and transcriptional activation. Together, these results suggest that the PLK1 inhibitor BI-2536 should be further investigated as a novel therapy for DKD.

16.
Biomed Res Int ; 2020: 5735279, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32884942

RESUMO

ALKBH5 (alkylation repair homolog protein 5), FTO (fat mass and obesity-associated protein), and RNA N6-methyladenosine (m6A) demethylase, are essential for the m6A mRNA modification. YTHDF2 (YT521-B homology domains 2) called m6A "readers" can recognize m6A modification. As the key enzymes of m6A methylation modification, ALKBH5, FTO, and YTHDF2 have been implicated in many diseases. However, little is known about the role of ALKBH5, FTO, and YTHDF2 in rheumatoid arthritis (RA). We measured the mRNA expression of ALKBH5, FTO, and YTHDF2 in RA patients and controls by quantitative real-time polymerase chain reaction, and the global m6A content was detected by an ELISA-like format. The mRNA expression of ALKBH5, FTO, and YTHDF2 in RA patients was further analyzed to investigate its correlations with disease activity. And, multivariate analysis (logistic regression) was used to analyze the risk factors. The mRNA expression of ALKBH5, FTO, and YTHDF2 in RA patients was significantly decreased compared to controls. The mRNA expression of ALKBH5 was significantly increased in RA patients that received regular treatment. The mRNA expression of FTO was associated with disease activity score 28 (DAS28), complement 3 (C3), immunoglobulin G (IgG), and lymphocyte-to-monocyte ratio (LMR), some common markers for RA disease activity. The mRNA expression of YTHDF2 was associated with RBC, L%, N%, NLR, and LMR. Furthermore, logistic regression analysis revealed that decreased expression of ALKBH5, FTO, and YTHDF2 in peripheral blood was a risk factor for RA. Moreover, the peripheral blood global m6A content was significantly increased in patients with RA compared to CON, and increased m6A contents negatively correlated with decreased mRNA expression of FTO. In conclusion, this study firstly demonstrates the critical role of ALKBH5, FTO, and YTHDF2 in RA, which provides novel insights into recognizing the pathogenesis of RA and a promising biomarker for RA.

17.
HPB (Oxford) ; 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32888851

RESUMO

BACKGROUND: As the most common biliary ducts, cholangiocarcinoma (CHOL) is an aggressive malignancy with complex pathological context, high mortality and relapse rate. The current therapy of CHOL is mainly performed with surgery followed by chemoradiotherapy. Due to the high metastasis and relapse rate of CHOL, the prognosis of CHOL is still poor, and the molecular prognostic system is to be constructed. METHODS: In this study, we have established an online prognostic analysis web server named OSchol to evaluate the correlation between candidate genes and survival for CHOL. RESULTS: The prognostic values of previous published biomarkers in OSchol, including ITIH4, PTEN and DACH1, have been validated by OSchol. In addition, we have identified novel potential prognostic biomarker for CHOL using OSchol, that E2F1 has significant prognostic ability in OSchol (both TCGA and GSE107943 cohorts). CONCLUSION: Our study provides a platform for researchers and clinicians to screen, develop and validate their genes of interest to be potential prognostic biomarkers for CHOL and may also help guide the targeted therapies for CHOL.

18.
Biol Trace Elem Res ; 2020 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-32893332

RESUMO

The original version of this article unfortunately contained a mistake. The name of "Yunzhen Chen" is now corrected in the author group.

19.
Artigo em Inglês | MEDLINE | ID: mdl-32870563

RESUMO

The catalytic asymmetric synthesis of the anti-COVID-19 drug remdesivir has been realized via the coupling of the P-racemic phosphoryl chloride with protected nucleoside GS441524. The chiral bicyclic imidazole catalyst is crucial for the dynamic kinetic asymmetric transformation (DyKAT) to proceed smoothly with high reactivity and excellent stereoselectivity [96% conv., 22:1 P(S):P(R)]. Mechanistic studies showed that this DyKAT is a first-order visual kinetic reaction dependent on catalyst concentration. The unique chiral bicyclic imidazole skeleton and carbamate substituent of the catalyst are both required for the racemization process involving the phosphoryl chloride and subsequent stereodiscriminating step. A 10-gram scale reaction was also conducted with comparably excellent results, showing its potential for industrial application.

20.
Artigo em Inglês | MEDLINE | ID: mdl-32875519

RESUMO

Pseudomonas aeruginosa (P. aeruginosa) keratitis is a sight-threatening and rapidly progressive corneal disease. Neutrophils and neutrophil extracellular traps (NETs) are widely thought to play a vital role in hosts' immune defenses against bacteria, such as P. aeruginosa. The present study aimed to investigate the dynamics of the formation and the role of NETs in P. aeruginosa keratitis. First, scratched corneas of mice models were treated with 1 × 108 colony-forming units (CFU)/ml of P. aeruginosa suspension or normal saline (NS). Second, after 48 h postinfection, the infected corneas were treated with TobraDex, Tobrex, 0.1% dexamethasone, or NS four times a day, respectively. Clinical examination, hematoxylin and eosin (H&E) staining, immunofluorescence staining, scanning electron microscopy, and bacterial burden testing were performed on the corneas. Tobrex reduced neutrophil infiltration and corneal P. aeruginosa burden. Dexamethasone reduced NETs, bacterial burden, and severe neutrophil infiltration. TobraDex produced a greater reduction in the amount of neutrophils, NETs, and bacterial burden and the results of Tobrex-treated group were between them. These findings corresponded with the clinical findings that TobraDex- and Tobrex-treated mice exhibited slight corneal damage, while dexamethasone-treated mice exhibited very severe corneal damage. Cumulatively, our data suggest that NETs may play a dual role of infection control and corneal damage in P. aeruginosa keratitis. Furthermore, combination treatment targeting NET formation and bacteria may serve as a way of improving the clinical outcomes of bacterial keratitis.

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