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1.
J Nucl Cardiol ; 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-33000403

RESUMO

BACKGROUND: Myocardial perfusion imaging (MPI) with a novel D-SPECT camera maintains excellent prognostic value compared to conventional SPECT. However, information about the relationship between D-SPECT MPI and the prognosis in patients with ischemia and no obstructive coronary artery disease (INOCA) is limited. The objective of this study was to evaluate the prognostic value of MPI with D-SPECT in INOCA and obstructive coronary artery disease (CAD) patients. METHODS: All consecutive patients with suspected CAD and without prior CAD who underwent D-SPECT MPI and invasive coronary angiography within 3 months were considered. INOCA and obstructive CAD were defined as < 50% and ≥ 50% coronary stenosis, respectively. Patients were followed-up for the occurrence of major adverse cardiac events (MACE: cardiovascular death, nonfatal myocardial infarction, revascularization, stroke, heart failure and angina-related rehospitalization). RESULTS: Among 506 patients, 232 (45.8%) were INOCA patients. A total of 33.2% of the INOCA patients had abnormal D-SPECT MPI, whereas 77.7% of the obstructive CAD patients had abnormal D-SPECT MPI. In both groups, patients with abnormal D-SPECT MPI demonstrated higher MACE rates and lower survival free of MACE. In addition, patients with INOCA and abnormal D-SPECT MPI had a poor prognosis similar to that of the obstructive CAD patients. Cox regression analysis showed that the risk-adjusted hazard ratios for abnormal D-SPECT MPI were 2.55 [1.11-5.87] and 2.06 [1.03-4.10] in the INOCA and obstructive CAD patients, respectively. CONCLUSIONS: D-SPECT MPI provides excellent prognostic information, with a more severe prognosis in patients with abnormal D-SPECT MPI. INOCA patients with abnormal D-SPECT MPI experience a poor prognosis similar to that of patients with obstructive CAD.

2.
G3 (Bethesda) ; 2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-33020192

RESUMO

The flySAM/CRISPRa system has recently emerged as a powerful tool for gain-of-function studies in Drosophila melanogaster This system includes Gal4/UAS-driven dCas9 activators and U6 promoter-controlled sgRNA. Having established dCas9 activators superior to other combinations, to further enhance the efficiency of the targeting activators we systematically optimized the parameters of the sgRNA. Interestingly, the most efficient sgRNAs were found to accumulate in the region from -150bp to -450bp upstream of the transcription start site (TSS), and the activation efficiency showed a strong positive correlation with the GC content of the sgRNA targeting sequence. In addition, the target region is dominant to the GC content, as sgRNAs targeting areas beyond -600bp from the TSS lose efficiency even when containing 75% GC. Surprisingly, when comparing the activities of sgRNAs targeting to either DNA strand, sgRNAs targeting to the non-template strand outperform those complementary to the template strand, both in cells and in vivo In summary, we define criteria for sgRNA design which will greatly facilitate the application of CRISPRa in gain-of-function studies.

3.
Chin J Integr Med ; 2020 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-33037518

RESUMO

OBJECTIVE: To evaluate whether the efficacy of Getong Tongluo Capsule (, GTC, consisted of total flavone of Radix Puerariae) on improving patients' quality of life and lowering blood pressure are superior to the extract of Ginkgo biloba (EGB) for patients with convalescent-phase ischemic stroke and primary hypertension. METHODS: This randomized, positive-drug- and placebo-controlled, double-blind trial was conducted from September 2015 to October 2017. Totally 477 eligible patients from 18 hospitals in China were randomly assigned in a 2:1:1 ratio to the following interventions, twice a day for 12 weeks: (1) GTC 250 mg plus EGB-matching placebo 40 mg (237 cases, GTC group), (2) EGB 40 mg plus GTC-matching placebo 250 mg (120 cases, EGB group) or (3) GTC-matching placebo 250 mg plus EGB-matching placebo 40 mg (120 cases, placebo group). Moreover, all patients were orally administered aspirin enteric-coated tablets 100 mg, once a day for 12 weeks. The primary outcome was the Barthel Index (BI). The secondary outcomes included the control rate of blood pressure and National Institutes of Health Stroke Scale (NIHSS) scores. The incidence and severity of adverse events (AEs) were calculated and assessed. RESULTS: The BI relative independence rates, the clinical recovery rates of NIHSS, and the total effective rates of NIHSS in the GTC and EGB groups were significantly higher than the placebo group at 12 weeks after treatment (P<0.05), and no statistical significance was found between the GTC and EGB groups (P>0.05). The control rate of blood pressure in the GTC group was significantly higher than the EGB and placebo groups at 12, 18 and 24 weeks after treatment (P<0.01). There were no statistically significant differences in the incidences of AEs, adverse drug reactions, or serious AEs among the 3 groups (P>0.05). CONCLUSION: GTC exhibited significant efficacy in improving patients' quality of life as well as neurological function and controlling hypertension. (Registration No. ChiCTR1800016667).

4.
Artigo em Inglês | MEDLINE | ID: mdl-33037783

RESUMO

OBJECTIVE: The objective of this study was to identify a sample of youth in distinct stages of risk for the development of a serious mental illness (SMI) according to a published clinical staging model and to follow this sample longitudinally to determine clinical changes over time. This article reports the 6- and 12-month follow-up of the cohort. METHODS: This study recruited 243 youth, ages 12 to 25. The sample included (a) 42 healthy controls, (b) 41 nonhelpseeking individuals with no mental illness but some risk of SMI, for example, having a first-degree relative with an SMI (stage 0), (c) 53 youth experiencing distress and mild symptoms of anxiety or depression (stage 1a), and (d) 107 youth with attenuated symptoms of SMIs such as bipolar disorder or psychosis (stage 1b). Participants completed a range of measures assessing depression, anxiety, mania, suicide ideation, attenuated psychotic symptoms, negative symptoms, anhedonia and beliefs about oneself at baseline, 6- and 12-months. RESULTS: There were few changes for healthy controls and stage 0 participants, although approximately 7% did move to a symptomatic stage within 12-months. Of stage 1a participants, 50% remained symptomatic, with 7.5% moving to stage 1b or developing a SMI. Approximately 9% of stage 1byouth developed a SMI within 12-months and approximately one-third had remission of symptoms during the follow-up. CONCLUSIONS: Results suggest that the implementation of a transdiagnostic staging model may be useful in youth mental health and support consideration of clinical stage-based treatment for youth with early features of risk.

5.
Int J Biol Macromol ; 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33038405

RESUMO

The structure of extracted condensed tannin (CT) from the fruit of Sour jujube (Ziziphus jujuba Mill. var. spinosa (Bunge) Hu ex H. F. Chow) and the molecular mechanisms by which CT inhibits the activity of mushroom tyrosinase were investigated. The structure of CT was characterized by high performance liquid chromatography electrospray ionization mass spectrometry, and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The kinetic assays were used to detect inhibition effect, type and mechanism. UV scanning, fluorescence quenching, copper interacting, o-quinone interaction and molecular docking assays were also used to reveal the molecular mechanisms by which CT inhibit tyrosinase. The results showed the main structural units of CT contain afzelechin/epiafzelechin, catechin/epicatechin, and atechin/epicatechin. Kinetic analysis showed that CT inhibits both the monophenolase and diphenolase activities of tyrosinase and exhibits reversible, mixed type mechanism. The fruit CT interacts primarily with the copper ions and specific amino acid residue (Asn191, Thr203, Ala202, Ser206, Met201, His194, His54, Glu182 and Ile42) in the active site of tyrosinase to disturb oxidation of substrates by tyrosinase. These results suggested the sour jujube fruit is a potential natural source of tyrosinase inhibitors, and has a potential to be used in food preservation, whitening cosmetics.

6.
Environ Sci Technol ; 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33044809

RESUMO

Bacterial deposition is the first step in the formation of microbial biofilms in environmental technology, and there is high interest in controlling such deposition. Earlier work indicated that direct current (DC) electric fields could influence bacterial deposition in percolation columns. Here, a time-resolved quartz crystal microbalance with dissipation monitoring (QCM-D) and microscopy-based cell counting were used to quantify DC field effects on the deposition of bacterial strains Pseudomonas putida KT2440 and Pseudomonas fluorescens LP6a at varying electrolyte concentrations and weak electric field strengths (0-2 V cm-1). DC-induced frequency shifts (Δf), dissipation energy (ΔD), and ratios thereof (Δf/ΔD) proved as good indicators of the rigidity of cell attachment. We interpreted QCM-D signals using a theoretical approach by calculating the attractive DLVO-force and the shear and drag forces acting on a bacterium near collector surfaces in a DC electric field. We found that changes in DC-induced deposition of bacteria depended on the relative strengths of electrophoretic drag and electro-osmotic shear forces. This could enable the prediction and electrokinetic control of microbial deposition on surfaces in natural and manmade ecosystems.

7.
Infect Immun ; 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33046511

RESUMO

Programmed cell death ligand-1 (PD-L1) is an immune checkpoint protein, which is used by tumor cells for immune evasion. PD-L1 is upregulated in inflamed intestinal tissues. The intestinal tract is colonized by millions of bacteria, most of which are commensal bacterial species. We hypothesize that under inflammatory conditions, some commensal bacterial species contribute to increased PD-L1 expression in intestinal epithelium and examined this hypothesis. Human intestinal epithelial HT-29 cells with and without interferon (IFN)-γ sensitization were incubated with six strains of four enteric bacterial species. The mRNA and protein levels of PD-L1 in HT-29 cells were examined using quantitative real-time PCR and flow cytometry, respectively. The levels of interleukin (IL)-1ß, IL-18, IL-6, IL-8 and tumor necrosis factor (TNF)-α secreted by HT-29 cells were measured using enzyme-linked immunosorbent assay. Apoptosis of HT-29 was measured using caspase 3/7 assay. We found that Escherichia coli (E. coli) K12 significantly upregulated both PD-L1 mRNA and protein in IFN-γ sensitized HT-29 cells. E. coli K12 induced the production of IL-8 in HT-29 cells, however, IL-8 did not affect HT-29 PD-L1 expression. Inhibition of the nuclear factor-kappa B pathway significantly reduced E. coli K12 induced PD-L1 expression in HT-29 cells. The other two E. coli strains and two enteric bacterial species did not significantly affect PD-L1 expression in HT-29 cells. Enterococcus faecalis significantly inhibited PD-L1 expression due to induction of cell death. Data from this study suggest that some gut bacterial species have the potential to affect immune function under inflammatory conditions via upregulating epithelial PD-L1 expression.

8.
Addict Biol ; : e12969, 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33047425

RESUMO

Internet gaming disorder (IGD), a worldwide mental health issue, has been widely studied using neuroimaging techniques during the last decade. Although dysfunctions in resting-state functional connectivity have been reported in IGD, mapping relationships from abnormal connectivity patterns to behavioral measures have not been fully investigated. Connectome-based predictive modeling (CPM)-a recently developed machine-learning approach-has been used to examine potential neural mechanisms in addictions and other psychiatric disorders. To identify the resting-state connections associated with IGD, we modified the CPM approach by replacing its core learning algorithm with a support vector machine. Resting-state functional magnetic resonance imaging (fMRI) data were acquired in 72 individuals with IGD and 41 healthy comparison participants. The modified CPM was conducted with respect to classification and regression. A comparison of whole-brain and network-based analyses showed that the default-mode network (DMN) is the most informative network in predicting IGD both in classification (individual identification accuracy = 78.76%) and regression (correspondence between predicted and actual psychometric scale score: r = 0.44, P < 0.001). To facilitate the characterization of the aberrant resting-state activity in the DMN, the identified networks have been mapped into a three-subsystem division of the DMN. Results suggest that individual differences in DMN function at rest could advance our understanding of IGD and variability in disorder etiology and intervention outcomes.

9.
Sci Rep ; 10(1): 17501, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33060756

RESUMO

Bacterial microcompartments (BMCs) are nanoscale proteinaceous organelles that encapsulate enzymes from the cytoplasm using an icosahedral protein shell that resembles viral capsids. Of particular interest are the carboxysomes (CBs), which sequester the CO2-fixing enzymes ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) to enhance carbon assimilation. The carboxysome shell serves as a semi-permeable barrier for passage of metabolites in and out of the carboxysome to enhance CO2 fixation. How the protein shell directs influx and efflux of molecules in an effective manner has remained elusive. Here we use molecular dynamics and umbrella sampling calculations to determine the free-energy profiles of the metabolic substrates, bicarbonate, CO2 and ribulose bisphosphate and the product 3-phosphoglycerate associated with their transition through the major carboxysome shell protein CcmK2. We elucidate the electrostatic charge-based permeability and key amino acid residues of CcmK2 functioning in mediating molecular transit through the central pore. Conformational changes of the loops forming the central pore may also be required for transit of specific metabolites. The importance of these in-silico findings is validated experimentally by site-directed mutagenesis of the key CcmK2 residue Serine 39. This study provides insight into the mechanism that mediates molecular transport through the shells of carboxysomes, applicable to other BMCs. It also offers a predictive approach to investigate and manipulate the shell permeability, with the intent of engineering BMC-based metabolic modules for new functions in synthetic biology.

10.
BMJ Open ; 10(10): e037514, 2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-33020094

RESUMO

INTRODUCTION: Cognitive behavioural therapy (CBT) is an evidence-based treatment for adults with attention deficit hyperactivity disorder (ADHD). However, it is still inconsistent whether a combination of CBT would have additive effects in medicated ADHD in adulthood. And if CBT would have additional effects, what kind and which dimension would CBT play a part? This study estimates the efficacy of CBT in stable medicated adult ADHD, using long-term outcomes and multidimensional evaluations. METHODS AND ANALYSIS: It is a two-armed, randomised controlled trial on the superiority of the efficacy of 12 weeks of CBT on medicated adult ADHD. We compare the short-term and long-term outcomes between CBT combined with medication (CBT+M) group and the medication-only (M) group, including ADHD core symptoms, emotional symptoms, executive function, self-esteem, life quality and brain function using functional near-infrared spectroscopy data. Participants are outpatients of the Peking University Sixth Hospital and those recruited online, diagnosed as adult ADHD and with stable medication treatment. We estimate ADHD core symptoms and combined symptoms at baseline (T1) and week 12 (T2), week 24 (T3), week 36 (T4) and week 48 (T5). ETHICS AND DISSEMINATION: This trial has been approved by the Ethics and Clinical Research Committees of Peking University Sixth Hospital and will be performed under the Declaration of Helsinki with the Medical Research Involving Human Subjects Act (WMO). The results will be disseminated in a peer-reviewed journal and a conference presentation. TRIAL REGISTRATION NUMBER: ChiCTR (ChiCTR1900021705).

11.
Chem Commun (Camb) ; 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33030195

RESUMO

A cancer cell targeted fluorescent viscosity probe has been designed and synthesized to specifically visualise viscosity changes in biotin receptor (BiR) positive cells over biotin negative cells via dual-mode fluorescence imaging: fluorescence intensity mode and fluorescence lifetime mode.

12.
BMC Bioinformatics ; 21(Suppl 14): 369, 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-32998686

RESUMO

BACKGROUND: Chromosome conformation capture-based methods, especially Hi-C, enable scientists to detect genome-wide chromatin interactions and study the spatial organization of chromatin, which plays important roles in gene expression regulation, DNA replication and repair etc. Thus, developing computational methods to unravel patterns behind the data becomes critical. Existing computational methods focus on intrachromosomal interactions and ignore interchromosomal interactions partly because there is no prior knowledge for interchromosomal interactions and the frequency of interchromosomal interactions is much lower while the search space is much larger. With the development of single-cell technologies, the advent of single-cell Hi-C makes interrogating the spatial structure of chromatin at single-cell resolution possible. It also brings a new type of frequency information, the number of single cells with chromatin interactions between two disjoint chromosome regions. RESULTS: Considering the lack of computational methods on interchromosomal interactions and the unsurprisingly frequent intrachromosomal interactions along the diagonal of a chromatin contact map, we propose a computational method dedicated to analyzing interchromosomal interactions of single-cell Hi-C with this new frequency information. To the best of our knowledge, our proposed tool is the first to identify regions with statistically frequent interchromosomal interactions at single-cell resolution. We demonstrate that the tool utilizing networks and binomial statistical tests can identify interesting structural regions through visualization, comparison and enrichment analysis and it also supports different configurations to provide users with flexibility. CONCLUSIONS: It will be a useful tool for analyzing single-cell Hi-C interchromosomal interactions.


Assuntos
Cromossomos/metabolismo , Análise de Célula Única/métodos , Animais , Cromatina/metabolismo , Fase G1 , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Camundongos , Células-Tronco Embrionárias Murinas/citologia , Células-Tronco Embrionárias Murinas/metabolismo , Oócitos/citologia , Oócitos/metabolismo , Fase S , Zigoto/citologia , Zigoto/metabolismo
13.
Int Immunopharmacol ; 89(Pt A): 106962, 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33039970

RESUMO

BACKGROUND: Neuroinflammation in the spinal cord following acute brachial plexus injury (BPI) remains a vital cause that leads to motor dysfunction and neuropathic pain. In this study, we aim to explore the role of long non-coding RNA JHDM1D antisense 1 (JHDM1D-AS1) in mediating BPI-induced neuroinflammation and neuronal injury. METHODS: A total brachial plexus root avulsion (tBPRA) model in adult rats and IL-1ß-treated motor neuron-like NSC-34 cells and LPS-treated microglia cell line BV2 were conducted for in vivo and in vitro experiments, respectively. The expressions of JHDM1D-AS1, miR-101-3p and DUSP1, p38, NF-κB, TNF-α, IL-1ß, and IL-6 were detected by RT-PCR and western blot seven days after tBPI. Immunohistochemistry (IHC) was used to detect neuronal apoptosis. CCK8 assay, Tunel assay and LDH kit were used for the detection of neuronal injury. The targeted relationships between JHDM1D-AS1 and miR-101-3p, miR-101-3p and DUSP1 were verified by RNA immunoprecipitation (RIP) and dual-luciferase reporter gene assay. RESULTS: We found significant downregulated expression of JHDM1D-AS1 and DUSP1 but upregulated expression of miR-101-3p in the spinal cord after tBPI. Overexpression of JHDM1D-AS1 had a prominent neuroprotective effect by suppressing neuronal apoptosis and microglial inflammation through reactivation of DUSP1. Further exploration revealed that JHDM1D-AS1 may act as a competitive endogenous RNA targeting miR-101-3p, which bound on the 3'UTR of DUSP1 mRNA. In addition, overexpression of miR-101-3p could reverse the neuroprotective effects of JHDM1D-AS1 upregulation by blocking DUSP1. CONCLUSIONS: JHDM1D-AS1 exerted neuroprotective and anti-inflammatory effects in a rat model of tBPI by regulating miR-101-3p/DUSP1 axis.

14.
Theranostics ; 10(25): 11520-11534, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33052230

RESUMO

Purpose: Clinical success of precision medicine is severely limited by de novo or acquired drug resistance. It remains a clinically unmet need to treat these patients. Tumor suppressor genes (TSGs) play a critical role in tumorigenesis and impact the therapeutic effect of various treatments. Experimental Design: Using clinical data, in vitro cell line data and in vivo mouse model data, we revealed the tumor suppressive role of Clusterin in lung cancer. We also delineated the signaling cascade elicited by loss of function of CLU in NSCLC cells and tested precision medicine for CLU deficient lung cancers. Results: CLU is a potent and clinically relevant TSG in lung cancer. Mechanistically, CLU inhibits TGFBR1 to recruit TRAF6/TAB2/TAK1 complex and thus inhibits activation of TAK1- NF-κB signaling axis. Lung cancer cells with loss of function of CLU show exquisite sensitivity to TAK1 inhibitors. Importantly, we show that a significant portion of Kras mutation positive NSCLC patients are concurrently deficient of CLU and that TAK1 kinase inhibitor synergizes with existing drugs to treat this portion of lung cancers patients. Conclusions: Combinational treatment with TAK1 inhibitor and MEK1/2 inhibitor effectively shrank Kras mutation positive and CLU deficient NSCLC tumors. Moreover, we put forward a concept that loss of function of a TSG rewires signaling network and thereby creates an Achilles' heel in tumor cells which could be exploited in precision medicine.

15.
Artigo em Inglês | MEDLINE | ID: mdl-33067789

RESUMO

Nanofiltration (NF) membranes show great potential for advanced water treatment, especially for trace organic pollutant removal. The removal efficiency of pharmaceuticals and personal care products (PPCPs) and environmental estrogenic hormones (EEHs) by positively charged hollow fiber NF membranes (PEI-NF) were evaluated. The separation properties were evaluated by changing the operating pressure, temperature, ionic strength, and cation species. A relationship between the physicochemical characteristics of the pharmaceuticals and the NF membrane retention behavior was established. The results showed that the rejection rates of the PEI-NF membrane for the selected PPCPs and EEHs ranged from 81 to ~ 91.26%. For positively (negatively) charged pharmaceutical molecules, the electrostatic repulsion (attraction) effect and steric hindrance were the dominant rejection mechanisms of the PEI-NF membrane. For neutral pharmaceutical molecules, in addition to the size sieving effect, the hydration-induced size increase of hydrophilic substances improved the rejection rates. Both the molecular structure and diffusion coefficient of pharmaceutical molecules influenced their rejection by the PEI-NF membrane to a certain extent. Moreover, the PEI-NF membrane showed a high removal effect for PPCPs and EEHs in water samples from actual tap water plants.

16.
Environ Res ; 192: 110282, 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33038361

RESUMO

Sulfate dependent ammonium oxidation (Sulfammox) is a potential microbial process coupling ammonium oxidation with sulfate reduction under anaerobic conditions, which provides a novel link between nitrogen and sulfur cycle. Recently, Sulfammox was detected in wastewater treatments and was confirmed to occur in natural environments, especially in marine sediments. However, knowledge gaps in the mechanism of Sulfammox, functional bacteria, and their metabolic pathway, make it challenging to estimate its environmental significance and potential applications. This review provides an overview of recent advances in Sulfammox, including possible mechanisms, functional bacteria, and main influential factors, and discusses future challenges and opportunities. Future perspectives are outlined and discussed, such as exploration of microbial community structure and metabolic pathways, possible interactions with other microbes, environmental significance, and potential applications for nitrogen and sulfate removal, to inspire more researches on the Sulfammox process.

17.
J Integr Med ; 2020 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-33069626

RESUMO

OBJECTIVE: Traditional Chinese medicine plays a significant role in the treatment of the pandemic of coronavirus disease 2019 (COVID-19). Tanreqing Capsule (TRQC) was used in the treatment of COVID-19 patients in the Shanghai Public Health Clinical Center. This study aimed to investigate the clinical efficacy of TRQC in the treatment of COVID-19. METHODS: A retrospective cohort study was conducted on 82 patients who had laboratory-confirmed mild and moderate COVID-19; patients were treated with TRQC in one designated hospital. The treatment and control groups consisted of 25 and 57 cases, respectively. The treatment group was given TRQC orally three times a day, three pills each time, in addition to conventional Western medicine treatments which were also administered to the control group. The clinical efficacy indicators, such as the negative conversion time of pharyngeal swab nucleic acid, the negative conversion time of fecal nucleic acid, the duration of negative conversion of pharyngeal-fecal nucleic acid, and the improvement in the level of immune indicators such as T-cell subsets (CD3, CD4 and CD45) were monitored. RESULTS: COVID-19 patients in the treatment group, compared to the control group, had a shorter negative conversion time of fecal nucleic acid (4 vs. 9 days, P = 0.047) and a shorter interval of negative conversion of pharyngeal-fecal nucleic acid (0 vs. 2 days, P = 0.042). The level of CD3+ T cells increased in the treatment group compared to the control group ([317.09 ± 274.39] vs. [175.02 ± 239.95] counts/µL, P = 0.030). No statistically significant differences were detected in the median improvement in levels of CD4+ T cells (173 vs. 107 counts/µL, P = 0.208) and CD45+ T cells (366 vs. 141 counts/µL, P = 0.117) between the treatment and control groups. CONCLUSION: Significant reductions in the negative conversion time of fecal nucleic acid and the duration of negative conversion of pharyngeal-fecal nucleic acid were identified in the treatment group as compared to the control group, illustrating the potential therapeutic benefits of using TRQC as a complement to conventional medicine in patients with mild and moderate COVID-19. The underlying mechanism may be related to the improved levels of the immune indicator CD3+ T cells.

18.
Artigo em Inglês | MEDLINE | ID: mdl-32997489

RESUMO

Poor prognosis of esophageal cancer is associated with limited clinical treatment efficacy and lack of targeted therapies. With advances in nanomedicine, nanoparticle drug delivery systems play increasingly important roles in tumor treatment by enabling the simultaneous delivery of multiple therapeutic agents. We here propose a novel nanovector for targeted combination gene therapy and chemotherapy in esophageal cancer. A novel lipid nanovector (EYLN) was designed to carry the chemotherapy drug doxorubicin (Dox) and small interfering RNA against the lipid anabolic metabolism gene LPCAT1, which we previously showed to be significantly overexpressed in esophageal cancer tissues, and its interference inhibited the proliferation, invasion, and metastasis of esophageal cancer cells. This vector, EYLN-Dox/siLPCAT1, was further coated with leukocyte membranes to obtain mEYLNs-Dox/siLPCAT1. The particle size of the coated nanovector was approximately 136 nm, and the surface zeta potential was -21.18 mV. Compared with EYLNs-Dox/siLPCAT1, mEYLNs-Dox/siLPCAT1 were more easily internalized by esophageal cancer cells due to the LFA-1 highly expressed leukocyte membrane coating and showed significant inhibition of the proliferation, migration, and metastasis of esophageal cancer cells, along with their LPCAT1 expression, through more effective delivery of the drugs. Moreover, the nanovectors showed improved blood circulation time, tissue distribution, tumor targeting, and tumor suppression in a mouse model. Thus, combining chemo and gene therapy with this new nanodelivery system achieved greater therapeutic efficacy, providing a new strategy for the treatment of esophageal cancer.

19.
BMC Cancer ; 20(1): 936, 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-32993568

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) is a common malignant tumor with characteristics of poor prognosis, high morbidity and mortality worldwide. In particular, only a few systemic treatment options are available for advanced HCC patients, and include sorafenib and the recently described atezolizumab plus bevacizumab regimen as possible first-line treatments. We here propose acteoside, a phenylethanoid glycoside widely distributed in many medicinal plants as a potential candidate against advanced HCC. METHODS: Cell proliferation, colony formation and migration were analyzed in the three human HCC cell lines BEL7404, HLF and JHH-7. Angiogenesis assay was performed using HUVESs. The BEL7404 or JHH-7 xenograft nude mice model was established to analyze the possible antitumor effects of acteoside. qRT-PCR and western blotting were used to reveal the potential antitumor mechanisms of acteoside. RESULTS: Acteoside inhibited cell proliferation, colony formation and migration in all the three human HCC cell lines BEL7404, HLF and JHH-7. The prohibition of angiogenesis by acteoside was revealed by the inhibition of tube formation and cell migration of HUVECs. The combination of acteoside and sorafenib produced stronger inhibition of cell colony formation and migration of the HCC cells as well as of angiogenesis of HUVECs. The in vivo antitumor efficacy of acteoside was further demonstrated in BEL7404 or JHH-7 xenograft nude mice model, with an enhancement when combined with sorafenib in inhibiting the growth of JHH-7 xenograft. Further treatment of JHH-7 cells with acteoside revealed an increase in the level of tumor suppressor protein p53 as well as a decrease of kallikrein-related peptidase (KLK1, 2, 4, 9 and 10) gene level with no significant changes of the rest of KLK1-15 genes. CONCLUSIONS: Acteoside exerts an antitumor effect possibly through its up-regulation of p53 levels as well as inhibition of KLK expression and angiogenesis. Acteoside could be useful as an adjunct in the treatment of advanced HCC in the clinic.

20.
Eur J Hosp Pharm ; 2020 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-32868386

RESUMO

BACKGROUND: Valproic acid (VPA) is a broad spectrum anticonvulsant drug, which could be partially metabolised by cytochrome P450 (CYP) 2C9 and 2C19 enzymes. This study was designed to investigate the relationship between CYP2C19 and CYP2C9 gene polymorphisms and the plasma concentrations of VPA in subjects with epilepsy. METHODS: Eighty-three subjects with epilepsy aged 18-92 years were enrolled in this study. All were treated with sustained-release VPA monotherapy. Based on the genotypes of CYP2C19 and the ability to metabolise substrates, the subjects were divided into poor metabolisers, intermediate metabolisers and extensive metabolisers. Sanger sequencing was used to detect the genotypic and allelic frequencies of CYP2C19 (*1, *2 and *3) and CYP2C9 (*13) of the patients. Automatic immunity analysis was used to find steady-state trough plasma concentrations of VPA. By adjusting the plasma concentrations of VPA with body weight and total daily dose of VPA, the concentration-to-dose ratio of VPA (CDRV) was obtained. Data were analysed using SPSS software. RESULTS: The genetic frequencies of CYP2C19*2, CYP2C19*3 and CYP2C9*13 were 33.1%, 3.0% and 5.4%, respectively, among patients with epilepsy from Yunnan province, China who used VPA therapy. The CDRV was significantly lower in the CYP2C19 extensive metabolisers (3.33±1.78) than it was in the CYP2C19 intermediate metabolisers (4.45±1.42) and the CYP2C19 poor metabolizers (6.64±1.06). The CYP2C19*2 and CYP2C19*3 alleles were correlated with the plasma VPA concentration, while the CYP2C9*13 allele had no effect on the plasma VPA concentration (p=0.809). CONCLUSIONS: The genetic polymorphisms of CYP2C19 significantly affect the VPA plasma concentration, and the dosage of VPA for intermediate and poor metabolisers could be lower than for extensive metabolisers. CYP2C9*13 carrier was not closely related to plasma concentrations of VPA in patients with epilepsy.

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