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1.
Life Sci ; : 118586, 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33065148

RESUMO

AIMS: Mitochondrial dysfunction is receiving considerable attention due to irreplaceable biological function of mitochondria. Ionizing radiation and tigecycline (TIG) alone can cause mitochondrial dysfunction, playing important role in tumor therapy. However, prior studies fail to investigate combined mechanism of carbon ion irradiation (IR) and TIG on tumor proliferation inhibition. The study aimed to explore the combined effects of both on autophagy and apoptosis. MATERIALS AND METHODS: NSCLC cells A549 and H1299 were treated with carbon ion, TIG, or both. Cell survival rate, autophagy, apoptosis, expression of mitochondrial signaling proteins were determined by clone formation assay, immunofluorescence of LC3B, flow cytometry and western blotting, respectively; ATP content, mitochondrial membrane potential (MMP) and Ca2+ level in mitochondria were used to assessed mitochondrial function. KEY FINDINGS: Results showed IR combined TIG inhibited cells proliferation by increasing apoptosis in both cells and enhancing autophagy in H1299 cells. Additionally, combination treatment induced the most severe mitochondrial dysfunction by sharply reducing ATP, MMP and increasing Ca2+ level of mitochondria. Up-regulation and down-regulation of mitochondrial translation proteins (EF-Tu, GFM1 and MRPS12) expression affected apoptosis and autophagy, while the level of p-mTOR was consistent with their expression in both cell types. In A549 cells, p-AMPK level decreased while p-Akt and p-mTOR increased after combination treatment. SIGNIFICANCE: Overall, our results showed that p-Akt and p-AMPK antagonistically targeted p-mTOR to regulate mitochondrial translation proteins to affect autophagy and apoptosis. Furthermore, this study suggests that combination of carbon ion and TIG is a potential therapeutic option against tumors.

2.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 1002-1006, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33018154

RESUMO

This research focuses on the gait phase recognition using different sEMG and EEG features. Seven healthy volunteers, 23-26 years old, were enrolled in this experiment. Seven phases of gait were divided by three-dimensional trajectory of lower limbs during treadmill walking and classified by Library for Support Vector Machines (LIBSVM). These gait phases include loading response, mid-stance, terminal Stance, pre-swing, initial swing, mid-swing, and terminal swing. Different sEMG and EEG features were assessed in this study. Gait phases of three kinds of walking speed were analyzed. Results showed that the slope sign change (SSC) and mean power frequency (MPF) of sEMG signals and SSC of EEG signals achieved higher accuracy of gait phase recognition than other features, and the accuracy are 95.58% (1.4 km/h), 97.63% (2.0 km/h) and 98.10% (2.6 km/h) respectively. Furthermore, the accuracy of gait phase recognition in the speed of 2.6 km/h is better than other walking speeds.

3.
J Affect Disord ; 279: 122-130, 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33045554

RESUMO

BACKGROUND: The Low Resistance Thought Induction Psychotherapy (TIP) is a comprehensive psychological treatment which could improve the clinical symptoms of major depressive disorder (MDD). However, the neural mechanisms for TIP treating MDD still remain unclear. This study aimed to investigate the topology of intrinsic connectivity network and the therapeutic effects of TIP in MDD on these topological properties. METHODS: Longitudinal study was conducted in 20 first-episode, treatment-naive MDD patients at baseline and after 6 weeks (12 sessions) of TIP treatment based on resting-state functional magnetic resonance image (rsfMRI) in conjunction with graph theoretical analysis. We constructed functional connectivity matrices and extracted the attribute features of the small-world networks in both MDD and age-, education level-, and gender-matched healthy controls (HCs). The global and local small-world network properties were explored and compared between MDD at baseline and HCs. The therapeutic effect of TIP was examined by comparing alterations in global and local network properties between MDD at baseline and after treatment. RESULTS: At baseline, MDD showed altered small-worldness and aberrant nodal properties in the frontolimbic circuit particularly in the orbital frontal gyrus, insula, precuneus and middle cingulate gyrus as compared with HCs. Following 6 weeks treatment, the abnormalities in the small-worldness and the nodal metrics were modulated, which were accompanied by a significant improvement in the clinical symptoms. CONCLUSIONS: Our findings contributed to the understanding of the abnormal topological patterns in the frontolimbic systems in MDD and implicated that these disruptions may be modified by TIP treatment.

4.
Medicine (Baltimore) ; 99(36): e22084, 2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-32899083

RESUMO

RATIONALE: Dabigatran is a direct thrombin inhibitor that is widely used to prevent the formation of thrombus formation. Amiodarone can increase the plasma concentration of dabigatran. CES1 (carboxylesterase 1) and ABCB1 (ATP-binding cassette subfamily B member 1) genetic polymorphisms associate with the pharmacokinetics of dabigatran. PATIENT CONCERNS: A 62-year-old woman was admitted to the hospital due to chest tightness, fatigue, and discomfort despite long-term anticoagulation with dabigatran 110 mg twice daily for 6 months, with concomitant use of amiodarone. DIAGNOSES: Left atrial appendage thrombus formation with a history of atrial fibrillation. INTERVENTIONS: The clinician changed dabigatran to warfarin. To explore the causes of insufficient anticoagulation using dabigatran in this patient, we examined the ABCB1 and CES1 genes. Results showed that she carried ABCB1 variant alleles with 3 heterozygote single nucleotide polymorphisms (SNPs: rs4148738, rs1045642, rs2032582) and CES1 variant alleles with 2 heterozygote SNPs (rs2244613, rs4580160). OUTCOMES: The left atrial appendage thrombus disappeared. LESSONS: Multiple mutations in the ABCB1 and CES1 genes may influence the pharmacokinetics of dabigatran and could have contributed to the thrombus formation in the left atrial appendage.


Assuntos
Apêndice Atrial/patologia , Fibrilação Atrial/complicações , Hidrolases de Éster Carboxílico/genética , Trombose/etiologia , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Antitrombinas/administração & dosagem , Antitrombinas/farmacocinética , Apêndice Atrial/diagnóstico por imagem , Dabigatrana/administração & dosagem , Dabigatrana/farmacocinética , Feminino , Humanos , Pessoa de Meia-Idade , Trombose/prevenção & controle
5.
Signal Transduct Target Ther ; 5(1): 194, 2020 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-32934199

RESUMO

Modulation of alloimmune responses is critical to improving transplant outcome and promoting long-term graft survival. To determine mechanisms by which a nonhematopoietic erythropoietin (EPO) derivative, carbamylated EPO (CEPO), regulates innate and adaptive immune cells and affects renal allograft survival, we utilized a rat model of fully MHC-mismatched kidney transplantation. CEPO administration markedly extended the survival time of kidney allografts compared with the transplant alone control group. This therapeutic effect was inhibited when the recipients were given LY294002, a selective inhibitor of the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway or anti-EPO receptor (EPOR) antibody, in addition to CEPO. In vitro, CEPO inhibited the differentiation and function of dendritic cells and modulated their production of pro-inflammatory and anti-inflammatory cytokines, along with activating the PI3K/AKT signaling pathway and increasing EPOR mRNA and protein expression by these innate immune cells. Moreover, after CD4+ T cells were exposed to CEPO the Th1/Th2 ratio decreased and the regulatory T cell (Treg)/Th17 ratio increased. These effects were abolished by LY294002 or anti-EPOR antibody, suggesting that CEPO regulates immune responses and promotes kidney allograft survival by activating the PI3K/AKT signaling pathway in an EPOR-dependent manner. The immunomodulatory and specific signaling pathway effects of CEPO identified in this study suggest a potential therapeutic approach to promoting kidney transplant survival.

6.
J Antibiot (Tokyo) ; 2020 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-32939075

RESUMO

Based on NH2-(AEEA)5-amphotericin B (DMR005; AEEA is 8-amino-3,6-dioxaoctanoic acid), a series of novel esterified and acylated derivatives of DMR005 were synthesized. These derivatives were evaluated for their antifungal activities using the broth dilution method, for their hemolytic toxicity with sterile defibrinated sheep blood, and for their self-association through UV-visible spectroscopy. The preliminary screening tests indicated that NH2-(AEEA)5-amphotericin B methyl ester (DMR031) was an ideal compound. The results of minimum inhibitory concentration and time-kill assays showed that antifungal activities of DMR031 (4 µg ml-1) against Candida albicans ATCC10231 and ATCC90028 were reduced by four times compared to these of amphotericin B (AmB) (1 µg ml-1). DMR031 (142 ± 1 mg ml-1) significantly improved the water solubility of AmB as DMR005 did. Preliminary safety assessments of DMR031 were carried out via cell toxicity assay of HEK293T in vitro, which turned out to be much better than AmB. AmB had good efficacy in vivo at a dose of 1 mg ml-1. However, DMR031 still had no efficacy in vivo even at a dose of 16 mg ml-1, merely prolonged the survival time of mice.

7.
Eur J Pharmacol ; 884: 173444, 2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-32739172

RESUMO

Sacubitril/valsartan (LCZ696) is recommended for ejection fraction reduction in heart failure. However, studies comparing the effects of sacubitril/valsartan in patients with heart failure and chronic kidney disease (CKD) with the inhibitor of renal angiotensin system (RAS) are limited. To further demonstrate the benefits of sacubitril/valsartan in patients with both heart failure and CKD, a meta-analysis of randomized controlled trials (RCTs) was conducted. The Cochrane Library, PubMed, Web of Science and ClinicalTrials.gov were searched for RCTs. A total of 3460 individuals with heart failure and CKD were included in this meta-analysis. Sacubitril/valsartan was compared with irbesartan, valsartan and enalapril. It was found that sacubitril/valsartan significantly increased estimated glomerular filtration rate [eGFR, MD = 1.90, 95% CI (0.30, 3.50), P = 0.02]. However, sacubitril/valsartan had no difference in urinary albumin/creatinine ratio [UACR, MD = -0.30, 95% CI (-1.38, 0.78), P = 0.59] compared to the control group. Sacubitril/valsartan showed dramatically decrease in systolic blood pressure [SBP, MD = -4.39, 95% CI (-6.11, -2.68), P < 0.001], diastolic blood pressure [DBP, MD = -2.69, 95% CI (-4.04, -1.35), P < 0.001], and N-terminal prohormone brain natriuretic peptide [NT-proBNP, MD = -45.34, 95% CI (-46.63, -44.06), P < 0.001]. There was no significant difference in the incidence of adverse reactions between sacubitril/valsartan and the control group. Compared with the RAS inhibitor, sacubitril/valsartan significantly increased eGFR and decreased BP and NT-proBNP, which indicates that it might have cardiovascular and renal benefits in patients with heart failure and CKD.

8.
Life Sci ; 258: 118176, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32771556

RESUMO

AIMS: We investigated the anti-inflammatory activity of 3ß-hydroxycholest-5-en-7-one from Hippocampus trimaculatus leach and provided a theoretical basis for identifying its therapeutic targets. MAIN METHODS: Small-RNA libraries were constructed for untreated control RAW 264.7 cells and cells treated with lipopolysaccharide (LPS; 1.0 µg/mL) or 10 µM 3ß-hydroxycholest-5-en-7-one +1.0 µg/mL LPS. We constructed and tested a miR-98-5p-interfering lentivirus to evaluate the role of miR-98-5p in the 3ß-hydroxycholest-5-en-7-one-dependent regulation of inflammatory responses in LPS-induced macrophage and murine inflammation models. The small-RNA libraries were analyzed using high-throughput sequencing. KEY FINDINGS: Among the differentially expressed microRNAs, miR-98-5p showed the most significant difference. Bioinformatics tools were used to identify the potential regulatory targets of miR-98-5p, which were tested using dual-luciferase reporter assays. Our results demonstrated that 3ß-hydroxycholest-5-en-7-one exerted an anti-inflammatory effect via miR-98-5p, which negatively regulated the expression of its target gene TNFAIP3. The results indicate that miR-98-5p interference and 3ß-hydroxycholest-5-en-7-one treatment significantly upregulated the low TNFAIP3 expression induced by LPS stimulation, thereby inhibiting TRAF6, RIP, NF-κB, IL-1ß, and TNF-α secretion. SIGNIFICANCE: 3ß-Hydroxycholest-5-en-7-one alleviates inflammation by downregulating miR-98-5p and upregulating TNFAIP3, thereby blocking NF-κB pathway activation. These results reveal the specific anti-inflammatory mechanism of 3ß-hydroxycholest-5-en-7-one, providing a foundation for developing new drugs and identifying drug targets.


Assuntos
Colestenonas/farmacologia , Regulação para Baixo/genética , Inflamação/patologia , MicroRNAs/metabolismo , Smegmamorpha/metabolismo , Regiões 3' não Traduzidas/genética , Animais , Colestenonas/química , Regulação para Baixo/efeitos dos fármacos , Genes Reporter , Inflamação/genética , Lentivirus/metabolismo , Lipopolissacarídeos , Luciferases/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , MicroRNAs/genética , Células RAW 264.7 , Reprodutibilidade dos Testes
9.
Acta Biochim Biophys Sin (Shanghai) ; 52(8): 791-800, 2020 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-32785592

RESUMO

MicroRNAs (miRNAs) are small non-coding RNAs that negatively regulate target mRNAs at the post-transcriptional level. Increasing evidence shows the involvement of miRNAs in diverse biological processes. miR-302/367 cluster is highly conserved among vertebrates and made up of five members, including miR-367, miR-302a, miR-302b, miR-302c and miR-302d. miR-302/367 cluster plays an important role in cell proliferation, differentiation and reprogramming, affecting the development of tumor, cardiovascular system, nervous system and immune system. In this review, we will summarize the role of miR-302/367 cluster in embryonic stem cells and induced pluripotent stem cells and try to point out its relationship with tumors, cardiovascular system, nervous system and immune system.

10.
J Neurol ; 2020 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-32601755

RESUMO

BACKGROUND: The aim of this study was to investigate differences in the dynamic changes and risk factors of hemodynamic depression (HD) between straight and tapered carotid stenting (SCS and TCS, respectively). METHODS: A total of 148 and 167 patients were included in TCS and SCS groups in this study, respectively. All clinical data were collected and analyzed for differences in HD and primary endpoint events at 12 months. RESULTS: The SCS procedure had a lower predilation rate and a higher incidence of intra- and postprocedure HD; furthermore, the decline in heart rate in the SCS procedure was higher in patients with intra- and postprocedure HD (P < 0.05). Right stenosis [odds ratio (OR) 1.67] and stent type (ev3) (OR 2.31) were confirmed as risk factors, and older age (> 70 years) was accompanied by a lower risk (OR 0.58; P < 0.05). The SCS procedure had a higher incidence of bradycardia and hypotension after 24 h and a longer duration of hypotension (P < 0.05). Stenosis (> 80%) (OR 1.68), the SCS procedure (OR 1.72), and alcohol intake (OR 2.38) were defined as risk factors. There was no difference in the complications or clinical endpoint events in either procedure, and the restenosis rate was lower in the TCS procedure (1.35% vs 5.42%). CONCLUSION: Our results reveal that TCS has a lower incidence of HD and that intra- and postprocedure HD have different manifestations and risk factors.

11.
J Cell Physiol ; 2020 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-32691425

RESUMO

Radiotherapy is one of the major modalities for malignancy treatment. High linear energy transfer (LET) charged-particle beams, like proton and carbon ions, exhibit favourable depth-dose distributions and radiobiological enhancement over conventional low-LET photon irradiation, thereby marking a new era in high precision medicine. Tumour cells have developed multicomponent signal transduction networks known as DNA damage responses (DDRs), which initiate cell-cycle checkpoints and induce double-strand break (DSB) repairs in the nucleus by nonhomologous end joining or homologous recombination pathways, to manage ionising radiation (IR)-induced DNA lesions. DNA damage induction and DSB repair pathways are reportedly dependent on the quality of radiation delivered. In this review, we summarise various types of DNA lesion and DSB repair mechanisms, upon irradiation with low and high-LET radiation, respectively. We also analyse factors influencing DNA repair efficiency. Inhibition of DNA damage repair pathways and dysfunctional cell-cycle checkpoint sensitises tumour cells to IR. Radio-sensitising agents, including DNA-PK inhibitors, Rad51 inhibitors, PARP inhibitors, ATM/ATR inhibitors, chk1 inhibitors, wee1 kinase inhibitors, Hsp90 inhibitors, and PI3K/AKT/mTOR inhibitors have been found to enhance cell killing by IR through interference with DDRs, cell-cycle arrest, or other cellular processes. The cotreatment of these inhibitors with IR may represent a promising therapeutic strategy for cancer.

12.
Life Sci ; 256: 117820, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32512012

RESUMO

Neuroblastoma (NB) is one of the most common malignant tumors in children. Chemotherapy resistance is one of the significant challenges in the treatment of high-risk NB patients, and it is necessary to search for new valid targets for NB treatment. This study aims to explore the possible role of PIF1 in NB by using bioinformatic analysis and downregulation of PIF1 with specific siRNA. Kyoto genome encyclopedia and R language based gene ontology was used to analyze the differentially expressed genes (DEGs) (including PIF1) when MYCN expression was silenced in NB cells. Analysis based on the R2 database showed a lower expression of PIF1 correlated with good prognosis in NB patients. Downregulation of MYCN expression by transfecting MYCN siRNA (#1, #2) into NB cells decreased the PIF1 expression at both mRNA and protein levels, while upregulation of MYCN expression by transfecting MYCN overexpressed plasmid increased the PIF1 expression. We further found that downregulation of PIF1 expression by transfecting PIF1 siRNA (#1, #2) into NB cells, increased the number of apoptotic cells, inhibited the cell survival, decreased the ability of cell migration and induced a cell cycle arrest at G1 phase. These data indicated that PIF1, as a potential new target of MYCN, maybe a novel target for NB treatment.


Assuntos
Apoptose/genética , Movimento Celular/genética , DNA Helicases/genética , Proteína Proto-Oncogênica N-Myc/genética , Neuroblastoma/patologia , Linhagem Celular Tumoral , Sobrevivência Celular/genética , Biologia Computacional , Regulação para Baixo , Regulação Neoplásica da Expressão Gênica , Humanos , Neuroblastoma/genética , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/genética , Regulação para Cima
13.
J Clin Pharm Ther ; 45(4): 602-608, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32449992

RESUMO

WHAT IS KNOWN AND OBJECTIVE: Low-molecular-weight heparin (LMWH) is widely used in the prevention and treatment of venous thromboembolism (VTE), and anti-Xa assay is the gold standard for monitoring LMWH. However, it is still controversial whether monitoring is necessary for patients receiving LMWH therapy. Therefore, we conducted a meta-analysis to explore the effect of anti-Xa monitoring on the safety and efficacy of LMWH anticoagulant therapy. METHODS: PubMed, EMBASE, Web of Science and The Cochrane Library were searched on 27 May 2019 for eligible studies published in English. Odds ratio (OR) and 95% confidence intervals (CI) were estimated (Mantel-Haenszel method) using Review Manager version 5.3 software. The systematic review and meta-analysis was performed according to the recommendations of the Preferred Reporting Items of Systematic Reviews and Meta-Analyses (PRISMA) statement. RESULTS AND DISCUSSION: Six studies involving 1617 patients were eligible for our meta-analysis, with 724 patients in the anti-Xa monitoring group and 893 patients in the control group. There was no significant difference in the incidence of bleeding events between the two groups, while the anti-Xa monitoring group had a lower incidence of venous thromboembolism events (OR 0.44, 95% CI 0.29-0.68, P = .0002). Subgroup analysis showed that the incidence of venous thromboembolism events in the anti-Xa monitoring group was lower than that in the control group when the trough level was monitored (OR 0.40, 95% CI 0.25-0.63, P < .0001), while there was no significant difference between the two groups when the peak level was monitored. WHAT IS NEW AND CONCLUSION: Patients receiving LMWH anticoagulant therapy to prevent VTE can benefit from anti-Xa monitoring, for which the trough level may be the more appropriate time status to monitor.

14.
Int J Clin Pharm ; 42(3): 861-870, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32410208

RESUMO

Background Although novel oral anticoagulants have been applied into clinical practice, warfarin remains the only approved oral anticoagulant for heart valve replacement. Currently, an increasing number of Chinese clinical pharmacists provide patients with warfarin education. However, little research to date has been carried out to evaluate the relationship between warfarin knowledge level and anticoagulation control among patients with heart valve replacement. Objective To evaluate knowledge of warfarin and the relationship between knowledge level and anticoagulation control among patients with heart valve replacement. Setting Fujian Medical University Union Hospital, China. Method A prospective and cross-sectional study was designed to evaluate the warfarin education of inpatients new to warfarin therapy using a validated Anticoagulation Knowledge Assessment questionnaire. Included patients were followed up for at least 3 months. Data were retrieved from hospital databases and telephone follow up. Main outcome measure Spearman's rho correlation analysis was used to assess the relationships between time in therapeutic range and warfarin knowledge level. Results 383 patients were included. The mean age of patients was 50.3 ± 7.9 years. The mean knowledge questionnaire score was 62.3 ± 8.8%. The majority of incorrect answers related to drug-warfarin interaction. Five of the frequently incorrect questions covered drugs, herbs and diet that affect warfarin therapy. There were significant correlations between total questionnaire score and time in therapeutic range (rho = 0.539, P < 0.001), or percentage of international normalized ratio measurements within range (rho = 0.416, P < 0.001). There were significant correlations between patients' educational level and total questionnaire score (rho = 0.357, P = 0.001). No significant correlations were found between income or living area and total questionnaire score (rho = 0.110, P = 0.435; rho = 0.161, P = 0.149). Conclusion Patient knowledge level of anticoagulation therapy affects anticoagulation control. Education for patients new to warfarin and the evaluation of knowledge by validated questionnaire is recommended for better INR control.

15.
Artigo em Inglês | MEDLINE | ID: mdl-32462540

RESUMO

Gastrointestinal bleeding is the most common bleeding complication during anticoagulant therapy. A reliable bleeding risk score can help the clinician assess risk of bleeding in individual patients and select the anticoagulant regimen. This study retrospectively analyzed the data of patients with atrial fibrillation who received anticoagulant therapy from July 2015 to December 2018 at two centers-the Fujian Medical University Union Hospital and Fuzhou Second Hospital Affiliated to Xiamen University. Demographic data, clinical findings, and laboratory results were collected from the hospital records. Patients were followed up for 6 months. The performance of four bleeding risk scores (New Score, RIETE Score, Cuschieri et al. Score, de Groot et al. Score) for prediction of gastrointestinal bleeding was assessed using the area under the curve. A total of 3462 patients (mean age, 66.3 ± 11.5 years; 59.6% males; 1055 direct oral anticoagulants users and 2407 warfarin users) were followed up for 6 months. While 99/3462 (2.9%) patients had gastrointestinal bleeding. The area under the curves for the New, RIETE, Cuschieri et al., de Groot et al. scores were 0.652 (95% CI 0.576-0.728), 0.862 (95% CI 0.809-0.914), 0.606 (95% CI 0.527-0.685), and 0.873 (95% CI 0.816-0.929), respectively. Among the four BRSs evaluated, the RIETE score and the de Groot et al. score appear to have the good predictive value, while the NEW score and the Cuschieri et al. score did not sufficiently predict gastrointestinal bleeding risk within the study Chinese population.

16.
ACS Synth Biol ; 9(6): 1385-1394, 2020 06 19.
Artigo em Inglês | MEDLINE | ID: mdl-32396719

RESUMO

The production of the aglycosylated immunoglobulin G (IgG) in Escherichia coli has received wide interest for its analytical and therapeutic applications. To enhance the production titer of IgG, we first used synthetic sRNAs to perform a systematical analysis of the gene expression in the translational level in the glycolytic pathway (module 1) and the tricarboxylic acid (TCA) cycle (module 2) to reveal the critical genes for the efficient IgG production. Second, to provide sufficient amino acid precursors for the protein biosynthesis, amino acid biosynthesis pathways (module 3) were enhanced to facilitate the IgG production. Upon integrated engineering of these genes in the three modules (module 1, aceF; module 2, gltA and acnA; module 3, serB) and optimization of fermentation conditions, the recombinant E. coli enabled a titer of the full-assembled IgG of 4.5 ± 0.6 mg/L in flask cultures and 184 ± 9.2 mg/L in the 5 L high cell density fed-batch fermenter, which is, as far as we know, the highest reported titer of IgG production in recombinant E. coli.

17.
Molecules ; 25(8)2020 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-32290627

RESUMO

Ultrasound-assisted extraction (UAE) was applied to extract rutin (RU), nicotiflorin (NI), narcissoside (NA), kaempferol (KA), isorhamnetin (IS), quercetin (QU), and total flavonoids of Flos Sophorae Immaturus (TFFSI) from Flos Sophorae Immaturus (FSI). Through single factor test and response surface methodology (RSM), the optimal extraction conditions were concluded as follows: ethanol concentration 70%, time 30 min, temperature 61 °C, and liquid/solid ratio 15.30 mL/g, respectively. The actual extraction rates of RU, NI, NA, KA, IS, QU, and TFFSI were 14.6101%, 2.9310%, 7.1987%, 0.1041%, 0.4920%, 2.7998%, and 26.4260%, respectively. The experimental results demonstrated that the extraction method with accuracy and efficiency could be used for the comprehensive evaluation quality control of extracts from FSI. The antioxidant activities of hydroalcoholic extraction from FSI on 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS•+), superoxide anion (•O2-) free radicals, and ferric reducing/antioxidant power (FRAP) were assessed. The results showed that the antioxidation activities of extracts on DPPH, ABTS•+, and •O2- free radicals were reached 89.29%, 97.86%, and 56.61%, and 81.4% in FRAP at 1.0 mg/mL, respectively. The antioxidant capacity of FSI extract was positively correlated with the amount of total flavonoids.

18.
Oncol Rep ; 44(1): 303-312, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32319660

RESUMO

The molecular mechanisms underlying the biological effects of carbon ions are unclear. The aim of this study was to explore the Wnt/ß­catenin pathway in regulating carbon ion (12C6+) radiation­induced cellular toxicity. HLY78 is a Wnt­specific small molecular modulator, whose effects on 12C6+ radiation­induced damage are mostly unknown. HLY78, in combination with 12C6+ radiation was investigated on HeLa cell viability, cell cycle progression, DNA damage, and the expression of apoptotic and Wnt­related proteins. 12C6+ radiation suppressed cell viability in a time­dependent manner, whereas the addition of HLY78 to cells significantly reduced this stress. Moreover, after irradiation with 12C6+, HeLa cells exhibited increased cell apoptosis, G2/M phase arrest, and a number of γ­H2AX foci. However, Wnt signaling activation alleviated these effects. Furthermore, when compared with the radiation alone group, supplementation with HLY78 markedly increased the expression of anti­apoptotic and Wnt­related proteins, and significantly decreased the expression of apoptotic proteins. The present results indicated that activation of the Wnt/ß­catenin signaling pathway by HLY78 reduced 12C6+ radiation­induced HeLa cell dysfunction, suggesting that the Wnt/ß­catenin signaling pathway plays an important role in regulating 12C6+ radiation­induced cellular toxicity in HeLa cells.

19.
Phytochemistry ; 175: 112378, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32315838

RESUMO

Submergence is one of the environmental stresses that limit plant growth and development. Dactylis glomerata L. is an important cool-season forage grass globally. To investigate the genes related to submergence response and the molecular mechanism associated with submergence tolerance, the transcriptome of D. glomerata in response to waterlogging treatment was analyzed. RNA-sequencing was performed in two D. glomerata cultivars, submergence tolerant 'Dianbei' and submergence sensitive 'Anba'. A total of 50,045 unique genes matched the known proteins in the NCBI nr database by BLAST searches and 60.8% (30,418) of these genes were annotated with GO terms. Among these, 1395 genes only differentially expressed in 'Dianbei' and 18 genes shown different expression all the time were detected between the submergence tolerant 'Dianbei' and sensitive 'Anba'. Gene ontology (GO) and KEGG pathway enrichment analyses demonstrated that the DEGs were mainly implicated in oxidation-reduction system, nucleic acid binding transcription factor activity, and glycerol kinase activity. The D. glomerata assembled transcriptome provided substantial molecular resource for further genomic analysis of forage grasses in response to submergence stress. The significant difference in expression of specific unigenes may account for waterlogging tolerance or acclimation in the two different D. glomerata cultivars. This study provided new insights into the molecular basis of submergence tolerance in D. glomerata.


Assuntos
Dactylis , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Ontologia Genética , Análise de Sequência de RNA , Transcriptoma
20.
Anal Chim Acta ; 1106: 1-21, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32145837

RESUMO

The preparation and practical applications of molecularly imprinted electrochemical sensors (MIECSs) remain challenging due to issues involving electrode surface renewal modes, low adsorption capacities, and sample preparation speeds. To solve these issues, magnetic molecularly imprinted electrochemical sensors (MMIECSs) have been extensively explored by various groups. Recently, MMIECSs fabricated based on diverse strategies have yielded insight into the development of MIECSs, and they have provided effective paths for sample preparation, immobilization and renewal of molecularly imprinted polymers (MIPs) on the electrode surface, leading to promising performances of MIECSs. This review comprehensively describes the research advances for various types of MMIECSs and their applications in the fields of food safety, environmental monitoring, and clinical and pharmaceutical analysis. Based on our understanding of MMIECSs, the literature in this field is thoroughly explored and classified in this review. The challenges existing in this research area and some potential strategies for the rational design of high-performance MMIECS are also outlined.

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