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1.
Int J Radiat Biol ; : 1-9, 2020 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-33164600

RESUMO

PURPOSE: Radioresistance is highly correlated with radiotherapy failure in clinical cancer treatment. In the current study, we sought to examine the efficacy of Celecoxib and Afatinib co-treatment as radiosensitizers in the management of non-small cell lung cancer (NSCLC) A549 cells. MATERIALS AND METHODS: Generally, A549 cells were cultured with the treatment of Celecoxib and/or Afatinib for 24 h. Then, the cells were exposed to irradiation at 2 Gy/min for 1 min. After the end of treatment, cell viability, clonogenic survival, apoptosis and Prostaglandin E2 (PGE2) Elisa assays were performed. Transcriptional levels of Cyclooxygenase-2 (COX-2) affected by Celecoxib and/or Afatinib were measured by RT-qPCR. Posttranscriptional level of epidermal growth factor receptor (EGFR)-related gene was measured by Western blotting analysis. RESULTS: Here, we, for the first time, reported that the co-treatment of Celecoxib and Afatinib regulates the resistance of NSCLC A549 cells to radiation. The co-treatment of Celecoxib and Afatinib sensitized radiotherapy through the radiation-induced loss of cell viability and colony formation, as well as apoptosis. Mechanistically, Celecoxib and Afatinib-treated cells showed the inhibition of COX-2 and EGFR expression, which may be responsible for the A549 cells' increased resistance to radiation. CONCLUSION: Our results suggested that Celecoxib and Afatinib regulate cell sensitivity to apoptosis, and thus modulate the resistance of NSCLC to radiation.

2.
Biophys J ; 2020 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-33130123

RESUMO

Although the folding of single-domain proteins is well characterized theoretically and experimentally, the folding of large multidomain proteins is less well known. Firefly luciferase, a 550 residue three-domain protein, has been commonly used as a substrate to study chaperone reactions and as a model system for the study of folding of long polypeptide chains, including related phenomena such as cotranslational folding. Despite being characterized by various experimental techniques, the atomic-level contributions of various secondary structures of luciferase to its fold's mechanical stability remain unknown. Here, we developed a piecewise approach for all-atom steered molecular dynamics simulations to examine specific secondary structures that resist mechanical unfolding while minimizing the amount of computational resources required by the large water box of standard all-atom steered molecular dynamics simulations. We validated the robustness of this approach with a small NI3C protein and used our approach to elucidate the specific secondary structures that provide the largest contributions to luciferase mechanostability. In doing so, we show that piecewise all-atom steered molecular dynamics simulations can provide novel atomic resolution details regarding mechanostability and can serve as a platform for novel mutagenesis studies as well as a point for comparison with high-resolution force spectroscopy experiments.

3.
Gene ; : 145305, 2020 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-33186614

RESUMO

High-altitude adaptation in Tibetan pigs (TP) is associated with positively-selected genes. The brain natriuretic peptide (BNP) gene is critical in the regulation of cardiovascular homeostasis and energy metabolism. The present study was conducted to identify the function of BNP for high-altitude adaptations in TP. RT-qPCR and western blotting results indicated that BNP expression could be upregulated when the pigs (especially for the Tibetan pigs) were raised to high altitude. In the 5' flanking region, three polymorphic sites, A-1964G, C-1780G, and T-940C were detected, and the genotype distribution of C-1780G was significantly different between the highland (TP) and lowland (Diannan small-eared pig; Yorkshire pig) breeds. The site of C-1780G was in active promoter regions identified using the luciferase reporter gene system, and the fragment with allele G had higher transcriptional activity than that with allele C. The TP population had a higher frequency of allele G than the two lowland breeds. Our results collectively demonstrated that the G allele of C-1780G in the BNP gene may be advantageous for high-altitude adaptation in pigs through upregulating BNP expression. Our findings provide information that helps toward a comprehensive understanding of the mechanism underlying the involvement of the BNP gene in high-altitude adaptation.

4.
Cancer Commun (Lond) ; 2020 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-33038291

RESUMO

BACKGROUND: Epigenetic regulation plays an important role in the development and progression of nasopharyngeal carcinoma (NPC). However, the epigenetic mechanisms underlying NPC metastasis remains poorly understood. We aimed to find functional genes which regulate the metastasis of NPC and identify therapeutic targets for NPC treatment. METHODS: Bisulfite pyrosequencing was used to analyze zinc finger protein 582 (ZNF582) methylation in NPC tissues and cell lines. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blotting were used to determine the expression of ZNF582. In vitro and in vivo experiments were performed to evaluate the biological function of ZNF582 in NPC. ZNF582-targeting genes were identified by chromatin immunoprecipitation sequencing (ChIP-seq) and were confirmed by ChIP-qPCR and luciferase assay. RESULTS: ZNF582 promoter was hypermethylated in NPC, and both the mRNA and protein levels of ZNF582 were down-regulated in NPC tissues and cell lines. The restoration of ZNF582 inhibited NPC migration, invasion, and metastasis, while the knockdown of ZNF582 promoted NPC migration, invasion, and metastasis in vitro and in vivo. ZNF582 directly regulated the transcription and expression of adhesion molecules Nectin-3 and NRXN3. Both Nectin-3 and NRXN3 were identified as functional targets of ZNF582, and the restoration or abrogation of these genes reversed the tumor suppressor effect of ZNF582 in NPC metastasis. CONCLUSIONS: ZNF582 acts as a tumor suppressor gene in NPC by regulating the transcription and expression of adhesion molecules Nectin-3 and NRXN3, which may provide novel therapeutic targets for NPC treatment.

5.
Heart Lung Circ ; 2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-33032892

RESUMO

BACKGROUND: Remote ischaemic conditioning (RIC) is an intervention that may exert a protective effect over multiple tissues or organs by regulating neuronal signal transduction. Heart rare variability (HRV) can assess the state of the autonomic nervous system. However, whether RIC can also regulate HRV in humans remains unknown. METHOD: This was a self-controlled interventional study in which serial beat-to-beat monitoring was performed at the same seven time points (7, 9, and 11 AM; 2, 5, and 8 PM; and 8 AM on the next day) with or without RIC in 50 healthy adults. The seven time points on the RIC day were defined as baseline, 1 hour, 3 hours, 6 hours, 9 hours, 12 hours, and 24 hours after RIC. The RIC protocol consisted of 4×5-minute inflation/deflation in one arm and one thigh cuff at 200 mmHg pressure from 7:20 to 8 AM. This study is registered on ClinicalTrials.gov (NCT02965547). RESULTS: We included 50 healthy adults volunteers (aged 34.54±12.01 years, 22 men [44%], all Asian). The variables analysed in frequency-domain measures performed as power of low-frequency in normalised units (0.04-0.15 Hz), high-frequency in normalised units (0.15-0.40 Hz), and ratio of low frequency to high frequency. The time-domain parameters standard deviation (SD) of all normal to normal (NN) intervals (SDNN), mean of the 5-minute SD of the NN intervals, SD of the consecutive 5-minute averages of NN intervals, and the root mean square of successive differences of NN intervals, and time-domain parameters calculated from Poincaré plots, SD of the short diagonal axis in Poincaré plot (SD1), SD of the long diagonal axis in Poincaré plot (SD2), and SD1/SD2 were also obtained. The SDNN and SD2 significantly increased 1 hour after RIC (p=0.029 and p=0.045, respectively). Additionally, the SD2 increased a second time 12 hours after RIC (p=0.041), which represented inhibited sympathetic activity. CONCLUSIONS: Heart rate variability increase and sympathetic inhibition induced by RIC appeared both on the early and delayed protective window of RIC, which may indicate some of the underlying mechanisms by which RIC may offer protection.

6.
Nat Prod Bioprospect ; 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33098068

RESUMO

Four new limonoids, toonayunnanaes F - I (1 - 4), and six known compounds (5 - 10) were isolated from the barks of Toona ciliata. Their structures were elucidated by thoroughly analyzing of NMR and HRMS data, and single-crystal X-ray diffraction of 1. The oxetane ring moiety in 1 was rare in limonoids and other natural products. Compound 1 showed nitric oxide (NO) inhibitory effect with an IC50 38.45 ± 0.41 µM in lipopolysaccharide (LPS)-activated RAW 264.7 macrophages.

7.
Yeast ; 2020 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-33125774

RESUMO

Mitochondrial division and fusion play critical roles in maintaining functional mitochondria. Fzo1 is an outer mitochondrial membrane GTPase that played an essential role in mitochondrial fusion in budding yeast Saccharomyces cerevisiae. Here, we report the characterization of the Schizosaccharomyces pombe homolog of S. cerevisiae Fzo1p, Fzo1. Disruption of the fzo1 gene in S. pombe results in a fragmented mitochondrial morphology and a dramatically reduced growth on glycerol medium phenotype, indicating that deletion of fzo1 compromises respiratory function. Fluorescence microscopy shows that Fzo1p is located in the mitochondria. Overexpressing Fzo1 from a heterologous promoter induces mitochondrial aggregation. We also find that dnm1 mutations could both block mitochondrial fragmentation and rescue respiration growth defect in Δfzo1 single mutant cells. Our results proposed that a genetic interaction between fzo1 and a balance between division and fusion controlled mitochondrial shape and function in S. pombe. This study represents the first report that Fzo1 mediator of mitochondrial fusion in S. pombe.

8.
PLoS Negl Trop Dis ; 14(10): e0008801, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33119592

RESUMO

Severe Fever with Thrombocytopenia Syndrome (SFTS) is an emerging infectious disease caused by a novel bunyavirus, SFTS virus (SFTSV), with fatal outcome developed in approximately 17% of the cases. Thrombocytopenia is a hallmark feature of SFTS, and associated with a higher risk of fatal outcome, however, the pathophysiological involvement of platelet in the clinical outcome of SFTS remained under-investigated. In the current study, by retrospectively analyzing 1538 confirmed SFTS patients, we observed that thrombocytopenia was associated with enhanced activation of the cytokine network and the vascular endothelium, also with a disturbed coagulation response. The platelet phenotypes were also extensively altered in the process of thrombocytopenia development of SFTS patients. More importantly, all these disturbed host responses were related to the severity of thrombocytopenia, thus were considered to play in a synergistic way to influence the disease outcome. Moreover, the clinical effect of platelet transfusion was assessed by comparing two groups of patients with or without receiving this therapy. As a result, we observed no therapy effect in altering frequencies of fatal outcome, clinical bleeding development, or dynamic change of platelet count during the hospitalization. It's suggested that platelet supplementation alone acted a minor role in improving disease outcome, therefore new therapeutic intervention to regulate host response should be proposed. The current results revealed some evidence of interrelationship between platelet count and clinical outcome of SFTS disease from the perspective of activation of the cytokine network, the vascular endothelium, and the coagulation/fibrinolysis system. These evaluations might help to attain a better understanding of the pathogenesis and therapy choice in SFTS.

9.
Artigo em Inglês | MEDLINE | ID: mdl-32975752

RESUMO

To high efficiently remove H2S from low partial pressure coke oven gas (COG), a novel activator (tetramethylammonium arginine, [N1111][Arg]) was used to blend with N-methyldiethanolamine (MDEA) for the absorption of H2S. High concentrated [N1111][Arg]-MDEA aqueous solution was used as absorbent. Thermodynamic properties including absorption amount and H2S loading values were measured, then the kinetic apparent absorption rate was calculated based on the change of absorption amount with time. The removal efficiency of H2S in simulated COG was verified in tray towers. Compared with monoethanolamine (MEA)-MDEA and tetramethylammonium glycinate ([N1111][Gly])-MDEA aqueous solutions, [N1111][Arg]-MDEA aqueous solution takes advantages of higher absorption capacity, absorption rate and removal efficiency. Our results showed that the proposed absorbent has good industrial application prospect in coke oven gas desulfurization, because it achieved 100% removal of H2S in the tray tower containing only 4 sieve plates under high concentrated condition (water content < 45%), which may significantly decrease the energy consumption.

10.
Ren Fail ; 42(1): 1004-1014, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32985309

RESUMO

BACKGROUND: Trimethylamine-N-Oxide (TMAO) is a proatherogenic and prothrombotic metabolite. Our study examined the association of plasma TMAO level with cardiovascular and all-cause mortality in hemodialysis (HD) patients. METHODS: Patients who were at least 18 years-old and received HD for at least 6 months were enrolled within 6 months. Patients with coronary heart disease, congestive heart failure, arrhythmia, or stroke within 3 months before study onset were excluded. The primary endpoints were cardiovascular and all-cause death, and the secondary endpoint was cerebrovascular death. RESULTS: We recruited 252 patients and divided them into a high-TMAO group (>4.73 µg/mL) and a low-TMAO group (≤4.73 µg/mL). The median follow-up time was 73.4 months (interquartile range: 42.9, 108). A total of 123 patients died, 39 from cardiovascular disease, 19 from cerebrovascular disease, and 65 from other causes. Kaplan-Meier analysis indicated that the high-TMAO group had a greater incidence of cardiovascular death (Log-Rank: p = 0.006) and all-cause death (Log-Rank: p < 0.001). Cox regression analysis showed that high TMAO level was significantly associated with cardiovascular and all-cause mortality. After adjustment for confounding, this association remained significant for cardiovascular mortality (TMAO as a continuous variable: HR: 1.18, 95%CI: 1.07, 1.294, p < 0.001; TMAO as a dichotomous variable: HR: 3.44, 95%CI: 1.68, 7.08, p < 0.001) and all-cause mortality (TMAO as a continuous variable: HR: 1.14, 95%CI: 1.08, 1.21, p < 0.001; TMAO as a dichotomous variable: HR: 2.54, 95%CI: 1.71, 3.76, p < 0.001). CONCLUSIONS: High plasma TMAO level is significantly and independently associated with cardiovascular and all-cause mortality in HD patients.

11.
Cell Biol Int ; 44(12): 2570-2587, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32910511

RESUMO

Circular RNA (circRNA) is a novel noncoding RNA that is mostly found in humans and animals. Although the flux of circRNA research has increased in recent years, its precise function is still unclear. Some studies demonstrate that circRNAs can function as microRNA (miRNA) sponges involved in the regulation of competitive endogenous RNAs networks and play a crucial role in many biological processes. Other studies show that circRNAs play multiple biological roles in gastrointestinal diseases. However, the expression characteristics and function of circRNA in intestinal mucosal injury and repair after severe burn have not been reported. This study aims to screen differentially expressed circRNAs in intestinal mucosal injury and repair after severe burns and understand their underlying mechanisms. To test our hypothesis that circRNA may play a role in promoting repair in intestinal mucosa injury after severe burns, we collected the intestinal tissues of three severely burned mice and three pseudo-scalded mice and evaluated the expression of circRNAs via microarray analysis. Quantitative real-time polymerase chain reaction was also used to validate the circRNA microarray data by selecting six based on different multiples, original values, and p values. The host genes of all differentially expressed circRNAs and the downstream target genes of six selected DEcircRNAs were identified by Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes pathway analysis. Meanwhile, we also created a circRNA-miRNA-mRNA network to predict the role and function of circRNAs in intestinal mucosal injury and repair after severe burns.

12.
Cancer Manag Res ; 12: 5903-5907, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32765091

RESUMO

Objective: This study investigates the effect of the standardized management of cancer pain on patients with bone metastasis of lung cancer in China. Patients and Methods: A total of 123 patients with bone metastasis of lung cancer were selected from the Respiratory Department of the Affiliated Hospital of North China University of Science and Technology. Among these patients, 62 patients who had not received standardized management of cancer pain from March 12, 2018, to September 11, 2018, were selected as the control group. In contrast, 61 patients who had received the standardized management of cancer pain from September 12, 2018, to March 11, 2019, were selected as the observation group. The former cohort accepted the conventional management of cancer pain, while the latter accepted the strict, standardized management of cancer pain. The demographic statistics, disease characteristics, and painkiller application of patients in these two groups were analyzed. Then, the analgesic effect and level of satisfaction were compared between these two groups. Results: No significant differences were noticed between these two groups in terms of age, gender, smoking status, type of pathology, education level, previous treatment, and the Eastern Cooperative Oncology Group score, as well as other demographic and disease characteristics. As for the use of painkillers, opioid analgesics accounted for a higher proportion in the observation group than in the control group. Compared with the control group, pain improvement and patient satisfaction after analgesic treatment were significantly higher in the observation group (p < 0.05). Conclusion: The standardized management of cancer pain can considerably alleviate the pain of patients with bone metastasis of lung cancer and improve their quality of life. Furthermore, this type of management can increase satisfaction.

13.
Phytochem Anal ; 2020 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-32744421

RESUMO

INTRODUCTION: Melia toosendan Sieb. et Zucc. has been used as a Chinese folk medicine for roundworm treatment since ancient times. Many diverse limonoids have been isolated from Meliaceae plants, but it remains difficult to isolate and identify other limonoids because of their small natural concentrations. OBJECTIVE: This study was performed to overcome the difficulties associated with fast and accurate identification of limonoids and establish a reliable and sensitive method for the analysis of minor limonoids in M. toosendan fruits. METHODS: An efficient strategy for enrichment, detection, and identification of minor limonoids from M. toosendan fruits using solid-phase extraction with high-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (SPE-HPLC-Q-TOF-MS/MS) was developed herein. RESULTS: Characteristic fragmentations and fragmentation ions containing trichilin-, nimbin-, and vilasinin-class limonoid skeletons were initially studied, and characteristic diagnostic ions involved retro Diels-Alder (RDA) reactions or homolytic cleavages, which were used to identify minor limonoids. In total, 13 limonoids, including four new ones, were identified. CONCLUSION: This is the first report on the analysis of M. toosendan fruits to identify limonoids. This novel analysis method may stimulate further research regarding the identification of limonoids in other plant species.

14.
Microorganisms ; 8(9)2020 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-32825672

RESUMO

The microbial community structure of water is an important indicator for evaluating the water quality of the aquaculture environment. In this study, the investigation and comparison of the bacterial communities of pond cultivation (PC) and greenhouse cultivation (GC) between hatchling, juvenile, and adult growth stages of C. reevesii were performed. In addition, the V4 regions of the 16S rRNA gene were sequenced. The Chao1 richness estimator of the PC group was significantly higher than that of the GC group. The beta diversity showed that the microbiotas of the two groups were isolated from each other. The dominant phyla were Cyanobacteria, Proteobacteria, Actinobacteria, Bacteroidetes, Verrucomicrobia, and Planctomycetes in the PC group and Proteobacteria, Bacteroidetes, Firmicutes, Cyanobacteria, Chloroflexi, and Actinobacteria in the GC group. Both the numbers and the types of Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotations differed between the PC and GC groups. The prediction of bacterial phenotype implied that the GC environment is more likely to deteriorate, and turtles are more susceptible to pathogens than those of the PC environment. In addition, a total of nine potential pathogenic bacteria were identified and the correlation of environmental factors analyses showed significant differences of bacterial species between the PC and GC groups, while the potential pathogenic bacteria showed significant correlation with the stocking density, temperature, pH, orthophosphate (PO4-P), and dissolved oxygen (DO) in both the PC and GC groups. Noticeably, this is the first report to describe the different microbiota characteristics of the different cultivation environments in the different growth stages of C. reevesii, which will provide valuable data for water quality adjustment, disease prevention, and the healthy breeding of turtles.

15.
Nutr Metab Cardiovasc Dis ; 30(11): 1980-1988, 2020 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-32807632

RESUMO

BACKGROUND AND AIMS: Cognitive behavioral therapy (CBT) is recommended as the first-line nonpharmacotherapy for sleep complaints. However, there are no studies that tested CBT for improving sleep quality and increasing quality of life (QOL) in patients with type 2 diabetes mellitus (T2DM). Therefore, this study aims to test the effect of CBT on sleep disturbances and QOL in patients with T2DM. METHODS AND RESULTS: In total, 187 participants with T2DM and comorbid poor sleep quality were included in the analysis with the control group of 93 receiving usual care (UC) only and the intervention group of 94 receiving CBT with aerobic exercise plus UC, The Pittsburgh Sleep Quality Index (PSQI), the Diabetes-Specific Quality of Life Scale (DSQLS) and the glycated hemoglobin (HbA1C) values were collected at baseline, after the 2-month intervention, and 6 months of follow-up. The CBT group had 3.03 points lower PSQI scores (95% confidence interval [CI]: 2.07-4.00, P < 0.001) and 7.92 points lower total DSQLS scores (95% CI: 4.98-10.87, P < 0.001) than the control group after 6-month follow-up. No difference was found in HbAlc between the two groups (t = -0.47, P = 0.64) after 2-month intervention, while the CBT group had 0.89 units lower HbAlc (95% CI: 0.49-1.28, P < 0.001) than the control group after 6-month follow-up. CONCLUSION: CBT is effective for sleep disturbances and can also improve sleep quality, increase QOL, and decrease glycemic levels in participants with T2DM. TRIAL REGISTRATION: Chinese Clinical Trials Registration (Practical study of the appropriate technique for improvement of quality of life of the patients with type 2 diabetes in communities: ChiCTR-IOP-16008045).

16.
Artigo em Inglês | MEDLINE | ID: mdl-32652831

RESUMO

We report a new mass spectrometric method for detecting electrogenerated intermediates. This approach is based on simultaneous activation of electrospray ionization and redox reaction on a wireless bipolar ultramicroelectrode, which is fabricated in the tip of a quartz nanopipette. The hollow structure of the ultramicroelectrode permits rapid transferring the transient species from electrode-electrolyte interfaces into the gas phase for mass spectrometric identification on the time scale of microseconds. The long-sought fleeting intermediates including TPrA.+ , whose lifetime in solution is only 200 µs, and catecholamine o-semiquinone radicals, the second-order rate constant of which is typically 109 m-1 s-1 , were successfully identified, helping clarify the previously hidden reaction pathways. Accordingly, our method may have wide applicability in exploring the dynamics of many electrochemical reactions, especially their ultrafast initial steps.

17.
Sci Rep ; 10(1): 11287, 2020 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-32647143

RESUMO

Establishment and maintenance of pregnancy depends on progesterone synthesized by luteal tissue in the ovary. Our objective was to identify the characteristics of lipid droplets (LDs) in ovarian steroidogenic cells. We hypothesized that LDs are a major feature of steroidogenic luteal cells and store cholesteryl esters. Whole bovine tissues, isolated ovarian steroidogenic cells (granulosa, theca, small luteal, and large luteal), and isolated luteal LDs were assessed for LD content, LD-associated proteins and lipid analyses. Bovine luteal tissue contained abundant lipid droplets, LD-associated perilipins 2/3/5, hormone-sensitive lipase, and 1-acylglycerol-3-phosphate O-acyltransferase ABHD5. Luteal tissue was enriched in triglycerides (TGs) compared to other tissues, except for adipose tissue. Luteal cells were distinguishable from follicular cells by the presence of LDs, LD-associated proteins, and increased TGs. Furthermore, LDs from large luteal cells were numerous and small; whereas, LDs from small luteal cells were large and less numerous. Isolated LDs contained nearly all of the TGs and cholesteryl esters present in luteal tissue. Isolated luteal LDs were composed primarily of TG, with lesser amounts of cholesteryl esters, diglyceride and other phospholipids. Bovine luteal LDs are distinct from LDs in other bovine tissues, including follicular steroidogenic cells.

18.
J Asian Nat Prod Res ; : 1-9, 2020 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-32619100

RESUMO

Two new (-)-epigallocatechin-3-gallate-4ß-triazolopodophyllotoxin conjugates (7 and 8) were synthesized and evaluated for biological activity. Compound 8 showed highly potent anticancer activity against A-549 cell line with IC50 of 2.16 ± 1.02 µM, which displayed the highest selectivity index value (SI = 14.5) in A-549 cells. Molecular docking indicated that compound 8 could bind with the active site of Top-II. Therefore, compound 8 might be a promising candidate for further development.

19.
Int J Mol Med ; 46(1): 384-396, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32626916

RESUMO

Neuritin plays an important role in neural development and plasticity. A recent study demonstrated that increasing Neuritin levels attenuated synaptic damage in mice with Alzheimer's disease (AD), which exhibit a decreased Neuritin expression. However, it remains unclear as to whether Neuritin expression is regulated by microRNAs (miRNAs or miRs) in AD. In the present study, it was found that miR­199a decreased Neuritin expression and was therefore involved in the development of AD. Subsequently, differentially expressed miRNAs in AD from datasets and the literature were recruited, and those that could bind Neuritin were predicted using bioinformatics analysis. The present study then focused on the candidate miRNAs that were highly associated with Neuritin and were upregulated in AD. The expression patterns of the candidate miRNAs and Neuritin in the hippocampus and cortex of APP/PS1 (AD model) mice at different stages were then detected and analyzed. It was found that miR­199a expression was significantly increased in the early stages of AD and was negatively associated with Neuritin expression. Furthermore, it was revealed that the decreased Neuritin expression was due to the direct targeting of the Neuritin 3'­UTR by miR­199a. Finally, the association between the spatial memory capacity of APP/PS1 mice and the changes in miR­199a and Neuritin expression protein was investigated. On the whole, the data of the present study suggest that miR­199a is involved in the development of AD by regulating Neuritin expression.

20.
BMC Plant Biol ; 20(1): 316, 2020 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-32631234

RESUMO

An amendment to this paper has been published and can be accessed via the original article.

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