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1.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(2): 474-488, 2021 Apr.
Artículo en Chino | MEDLINE | ID: mdl-33812418

RESUMEN

OBJECTIVE: To investigate the effect and mechanism of a novel emodin derivative YX-18 on Burkitt lymphoma (BL) cells. METHODS: MTT assay was used to detect the effect of YX-18 on the proliferation of BL cell lines CA46 and Raji. Annexin V-PE/7-AAD double staining assay was used for detecting the effect of YX-18 on the apoptosis of CA46 and Raji cells. PI/RNase staining was used to test the effect of YX-18 on CA46 and Raji cell cycle. JC-1 method was used to measure the changes of mitochondrial membrane potential after YX-18 treatment, and DAPI staining was used to detect the morphology of apoptotic cells. Western blot was used to analyze the distribution changes of NF-κB pathway protein (P65, P-P65, IκB, P-IκB) in the cytoplasm and cell nucleus, and also the expression changes of cyclin-related protein P21, CDK2, P-CDK2, Cycling D1, Cycling E1, and the apoptosis-related protein Caspase-3, Caspase-8, Caspase-9 and the proliferation-related protein C-MYC, BCL-2 by YX-18. Real-time fluorescence-quantitative PCR was used to evaluate the effects of YX-18 on mRNA levels of C-MYC and Ki-67 genes in CA46 and Raji cells, and EBNA-1 and EBER genes of EBV in Raji (EBV+) cells. RESULTS: Novel Emodin derivative YX-18 could effectively inhibit the proliferation of BL cell lines CA46 and Raji, showing a time-dependent effect (24, 48 and 72 h: rCA46=0.89, 0.75, 0.75, rRaji=0.87, 0.73, 0.64). IC50 of CA46 cells and Raji cells treated with YX-18 for 24 h was 1.77±0.04 µmol/L and 1.97±0.22µmol/L, respectively. CA46 cells and Raji cells were treated with YX-18 at concentration of 2.0 and 4.0 µmol/L for 24 h. Compared with the control group, both strains of cells showed a very significant apoptosis at the concentration of 2.0 and 4.0 µmol/L (P<0.01), showing a concentration-dependent effect (rCA46=0.99, rRaji=0.92). Moreover, the cleavaged Caspase-3, 8 and 9 proteins were activated by YX-18 into verious degrees in both two cell lines. Both the two cell lines displayed by YX-18 cell cycle arrest at G0/G1 phase (P<0.01) after exposed to YX-18 for 24 hours at the concentration of 1.0, 2.0 µmol/L in CA46 cells and at 0.5 and 1 µmol/L in Raji cells, respectively. YX-18 decreased expression level of cyclin D1, cyclin E1, CDK2, p-cdk2 proteins and increased p21Waf1/Cip1 level in CA46 and Raji cells. YX-18 significantly declined mitochondrial membrane potential in both cells at the concentration of 2.0 and 4.0 µmol/l (P<0.01) with concentration-dependent manner (rCA46=-0.96, rRaji=-0.99). Western blot tests indicated that YX-18 down-regulated nucleus P65 and intracellular cytoplasm P65, P-IκB, P-P65 protein, and upregulated intracellular IκB level with dose-dependent manner. Meanwhile, the expression level of the cell proliferation-related molecules C-MYC and BCL-2 was decreased significantly. YX-18 suppressed mRNA levels of C-MYC and Ki-67 in both cell lines, and EBNA-1 in EBV-positive Raji cells in a concentration-dependent way. CONCLUSION: The novel emodin derivative YX-18 can significantly inhibit the proliferation of Burkitt lymphoma cells, and induce the cell apoptosis and cycle arrest. The inhibitory effect of YX-18 on the proliferation of Burkitt lymphoma cells may be related with the effect of Caspase apoptosis pathway, the proliferation and apoptosis-related molecules, such as C-MYC and Ki-67, and also to the inhibition of NF-κB pathway.


Asunto(s)
Linfoma de Burkitt , Emodina , Apoptosis , Ciclo Celular , Línea Celular Tumoral , Proliferación Celular , Emodina/farmacología , Humanos , FN-kappa B
2.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(2): 574-580, 2021 Apr.
Artículo en Chino | MEDLINE | ID: mdl-33812433

RESUMEN

OBJECTIVE: To investigate the factors affecting the chronicity of childhood primary immune thrombo-cytopenia (ITP) and compare the efficiency of different first-line treatment regimens. METHODS: Children with ITP hospitalized in our hospital from September 2013 to October 2018 were retrospectively analyzed. RESULTS: Three hundred and one children (150 males and 151 females) were included in this study, with a median age of 8 (0.17-17) years old, and 110 (36.5%), 92 (30.6%), and 99 (32.9%) cases were grouped into newly diagnosed, persistent, and chronic ITP, respectively. The median of follow-up was 41.92 (1.07-74.03) months. At the end of the follow-up (October 2019), among the 202 newly diagnosed/persistent ITP children, 79 cases (59 newly diagnosed and 20 persistent ITP) achieved remission within 1 year after initial diagnosis, with a remission rate of 39.3%; 122 cases (50 newly diagnosed and 72 persistent ITP) developed chronic disease, with a chronicity rate of 60.7%; one case underwent splenectomy. In 99 cases with chronic ITP, 5 cases underwent splenectomy. Multivariable logistic regression analysis showed that, the insidious onset of symptoms (OR=3.754, 95%CI: 1.882-7.488, P=0.000) increased the risk of chronicity, while the positive antibody to anti-platelet membrane glycoprotein (OR=0.446, 95%CI: 0.224-0.888, P=0.021) might reduce the risk of chronicity. And no difference was found by the analysis of subtype of anti-platelet membrane glycoprotein (P=0.305). The efficacy of the first-line treatment of intravenous immunoglobulin (IVIG) alone or combined with steroid was better than that of steroid alone (P=0.028, 0.028), however, the efficiency was not significantly different between IVIG alone and combined with steroid (P=0.086). CONCLUSION: Insidious onset of symptoms in pediatric ITP increases the risk of chronicity, while the positive titer of anti-platelet membrane glycoprotein may reduce the risk. In the first-line treatment for the newly diagnosed/persistent children. The efficacy of IVIG alone or combined with steroid is better than that of steroid alone.


Asunto(s)
Púrpura Trombocitopénica Idiopática , Adolescente , Niño , Niño Hospitalizado , Femenino , Humanos , Inmunoglobulinas Intravenosas , Masculino , Estudios Retrospectivos , Esplenectomía
3.
Pest Manag Sci ; 2021 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-33798270

RESUMEN

BACKGROUND: In Drosophila, the sex peptide receptor (SPR) in females to detect male sex peptide (SP) and trigger changes in female behavior including mating rejection and oviposition. In moths, the SPR had been identified and investigated the limited function by using RNAi. However, the detailed function of SPR after a normal mating in moths, especially the role in female sexual receptivity, remains to be elucidated. RESULTS: In this study, we use Helicoverpa armigera, an economically important pest worldwide, as a case study to verify the function of SPR in vivo by CRISPR/Cas9 gene editing system. Analyzing the post-mating behaviors in mutant females, we investigated that HarmSPR could mediate the long-term sexual receptivity (remating, sex pheromone production and calling behavior) switch in female, but not affect the short-term sexual receptivity and the duration time of remating. The oviposition of mated HarmSPR-/- females was significantly decreased by ~70% comparing to WT mated females and there were more eggs staying in the ovary of mutant females. SPR also showed effect on female longevity, which is that the mated HarmSPR-/- females showed longer longevity than mated WT females. CONCLUSION: The results detailedly demonstrated the functional role of SPR in female post-mating behaviors and we could propose a pest control strategy in which developing a antagonist of SPR to reduce the oviposition of female. This article is protected by copyright. All rights reserved.

4.
Bioorg Chem ; 111: 104847, 2021 Mar 22.
Artículo en Inglés | MEDLINE | ID: mdl-33798849

RESUMEN

Diabetes mellitus is caused by chronic inflammation and affects millions of people worldwide. Cyclocarya paliurus leaves have been widely used in traditional folk tea as a remedy for diabetes, but the antidiabetic constituents remain to be further studied. The α-glucosidase inhibitory and anti-inflammatory activities were examined to evaluate their effects on diabetes mellitus, and bioassay-guided separation of C. paliurus leaves led to the identification of twenty dammarane saponins, including eleven new dammarane saponins (1-11). The structures of the isolates were elucidated by spectroscopic methods. Bioactivity assay results showed that compounds 1 and 2 strongly inhibited α-glucosidase activity, with IC50 values ranging from 257.74 µM, 282.23 µM, and strongly inhibited the release of NO, with IC50 values of 9.10 µM, 9.02 µM. Moreover, compound 2 significantly downregulated the mRNA expression of iNOS, COX-2, IL-1ß, NF-κB, IL-6 and TNF-α in LPS-mediated RAW 264.7 cells and markedly suppressed the protein expression of iNOS, NF-κB/p65, and COX-2. Dammarane glucoside 2 exhibited the strongest α-glucosidase inhibitory and anti-inflammatory activities. In addition, the structure-activity relationships (SARs) of the dammarane saponins were investigated. In summary, C. paliurus leaves showed marked α-glucosidase inhibitory and anti-inflammatory activities, and dammarane saponins are responsible for regulating α-glucosidase, inflammatory mediators, and mRNA and the protein expression of proinflammatory cytokines, which could be meaningful for discovering new antidiabetic agents.

5.
Entropy (Basel) ; 23(3)2021 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-33799388

RESUMEN

Decentralization is a peculiar characteristic of self-organizing systems such as swarm intelligence systems, which function as complex collective responsive systems without central control and operates based on contextual local coordination among relatively simple individual systems. The decentralized particularity of self-organizing systems lies in their capacity to spontaneously respond to accommodate environmental changes in a cooperative manner without external control. However, if members cannot obtain observations of the state of the whole team and environment, they have to share their knowledge and policies with each other through communication in order to adapt to the environment appropriately. In this paper, we propose an information sharing mechanism as an independent decision phase to improve individual members' joint adaption to the world to fulfill an optimal self-organization in general. We design the information sharing decision analogous to human information sharing mechanisms. In this case, information can be shared among individual members by evaluating the semantic relationship of information based on ontology graph and their local knowledge. That is, if individual member collects more relevant information, the information will be used to update its local knowledge and improve sharing relevant information by measuring the ontological relevance. This will enable more related information to be acquired so that their models will be reinforced for more precise information sharing. Our simulations and experimental results show that this design can share information efficiently to achieve optimal adaptive self-organizing systems.

6.
Polymers (Basel) ; 13(6)2021 Mar 11.
Artículo en Inglés | MEDLINE | ID: mdl-33799623

RESUMEN

RNA-based molecules have recently become hot candidates to be developed into therapeutic agents. However, successful applications of RNA-based therapeutics might require suitable carriers to protect the RNA from enzymatic degradation by ubiquitous RNases in vivo. Because of their better biocompatibility and biodegradability, protein-based nanoparticles are considered to be alternatives to their synthetic polymer-based counterparts for drug delivery. Hepatitis C virus (HCV) core protein has been suggested to be able to self-assemble into nucleocapsid-like particles in vitro. In this study, the genomic RNA-binding domain of HCV core protein consisting of 116 amino acids (p116) was overexpressed with E. coli for investigation. The recombinant p116 was able to assemble into particles with an average diameter of approximately 27 nm, as visualized by electron microscopy and atomic force microscopy. Measurements with fluorescence spectroscopy, flow cytometry, and fluorescence quenching indicated that the p116-assembled nanoparticles were able to encapsulate small anionic molecules and structured RNA. This study demonstrates methods that exploit the self-assembly nature of a virus-derived protein for nanoparticle production. This study also suggests that the virus-derived protein-assembled particles could possibly be developed into potential carriers for anionic molecular drugs and structured RNA-based therapeutics.

7.
Plants (Basel) ; 10(3)2021 Mar 13.
Artículo en Inglés | MEDLINE | ID: mdl-33805780

RESUMEN

As a potential energy crop with high biomass yield, Miscanthus lutarioriparius (M. lutarioriparius), endemic to the Long River Range in central China, needs to be investigated for its acclimation to stressful climatic and soil conditions often found on the marginal land. In this study, traits related to acclimation and yield, including survival rates, plant height (PH), stem diameter (SD), tiller number (TN), water use efficiency (WUE), and photosynthetic rates (A), were examined for 41 M. lutarioriparius populations that transplanted to the arid and cold Loess Plateau of China. The results showed that the average survival rate of M. lutarioriparius populations was only 4.16% over the first winter but the overwinter rate increased to 35.03% after the second winter, suggesting that plants having survived the first winter could have acclaimed to the low temperature. The strikingly high survival rates over the second winter were found to be 95.83% and 80.85%, respectively, for HG18 and HG39 populations. These populations might be especially valuable for the selection of energy crops for such an area. Those individuals surviving for the two consecutive winters showed significantly higher WUE than those measured after the first winter. The high WUE and low stomatal conductance (gs) observed in survived individuals could have been responsible for their acclimation to this new and harsh environment. A total of 61 individuals with productive growth traits and strong resistance to cold and drought were identified for further energy crop development. This study showed that the variation of M. lutarioriparius held great potential for developing energy crops following continuous field selection.

8.
Materials (Basel) ; 14(6)2021 Mar 13.
Artículo en Inglés | MEDLINE | ID: mdl-33805822

RESUMEN

In this study, the structural, elastic, and thermodynamic properties of DO19 and L12 structured Co3X (X = W, Mo or both W and Mo) and µ structured Co7X6 were investigated using the density functional theory implemented in the pseudo-potential plane wave. The obtained lattice constants were observed to be in good agreement with the available experimental data. With respect to the calculated mechanical properties and Poisson's ratio, the DO19-Co3X, L12-Co3X, and µ-Co7X6 compounds were noted to be mechanically stable and possessed an optimal ductile behavior; however, L12-Co3X exhibited higher strength and brittleness than DO19-Co3X. Moreover, the quasi-harmonic Debye-Grüneisen approach was confirmed to be valid in describing the temperature-dependent thermodynamic properties of the Co3X and Co7X6 compounds, including heat capacity, vibrational entropy, and Gibbs free energy. Based on the calculated Gibbs free energy of DO19-Co3X and L12-Co7X6, the phase transformation temperatures for DO19-Co3X to L12-Co7X6 were determined and obtained values were noted to match well with the experiment results.

9.
Animals (Basel) ; 11(3)2021 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-33807718

RESUMEN

One of the most important factors that determine feed utilization by chickens is the feed form. Although it is generally believed that pellet diets have a positive effect on chicken growth, there are some studies that have indicated no difference between pellet and mash on chickens performance. This study was conducted to assess the effects of feed form on production performance, egg quality, nutrient metabolism and intestinal morphology in two breed laying hens. Two hundred and sixteen 25-week-old Hy-Line brown (n = 108) and Hy-Line grey (n = 108) hens were selected. Each breed was randomly allocated into two treatments with 6 replications (9 birds in each replication), which were fed mash and pellet diets, respectively. Production performances were recorded daily and egg quality traits were measured every two weeks. At 42 weeks of age, one bird per replication from each experimental group was selected for metabolism determination and intestine morphology observation. Compared with mash diets, pellet diets improved laying rate (p < 0.05), ADFI (average daily feed intake, p < 0.05), egg weight, shell strength, yolk proportion and Haugh unit (p < 0.05) in both breeds and reduced the FCR (feed conversion ratio, p < 0.05) in Hy-Line grey. The apparent digestibility of DM% (dry matter) and CP% (crude protein) were significantly higher (p < 0.05) in both breed laying hens fed pellet than those fed mash. The apparent digestibility of P% (phosphorus) and Ca% (calcium) was higher in Hy-Line grey fed pellet and was higher in Hy-Line brown fed mash. Compared to mash diets, pellet diets increased the VH (villus height), CD (crypt depth) and VCR (ratio of villus height to crypt depth) of the small intestine of Hy-Line grey, and increased the VH and CD of duodenum and ileum of Hy-Line brown. Overall, pellet diets improved production performance and nutrition metabolism through positive changes in the laying rate, feed intake, egg albumen quality and apparent digestibility of laying hens. The current findings provided support for the advantages of feeding pellets during the peak egg laying period for the two popular laying hen strains, Hy-Line brown and Hy-Line grey.

10.
Acta Diabetol ; 2021 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-33811294

RESUMEN

AIMS: To quantify hard exudates (HEs) by multicolor imaging (MCI) and traditional color fundus photography (CFP) in diabetic macular edema (DME), and study their associations with serum lipid levels. METHODS: Observational study. DME patients with HEs were recruited. The HE area and location both by MCI and CFP were measured by ImageJ software. Multivariate regression models were used to analyze the associations of serum lipid levels with the total HE area and HE location. RESULTS: Sixty-two patients (74 eyes) were enrolled to quantify HEs in DME. The total HE area by MCI was larger than that by CFP (P = 0.004), and the distance between the fovea and the nearest HE by MCI was shorter than that by CFP (P = 0.003). The percentage of patients with HEs involving the central macula by MCI was significantly higher than that by CFP (P < 0.001). Furthermore, 62 eyes of 62 patients were included to analyze the associations of HE parameters with serum lipid levels. In both MCI and CFP, the HE areas were positively associated with triglyceride level (P = 0.016, P = 0.022, respectively). HEs involving the central macula were positively associated with triglyceride and low-density cholesterol levels in MCI (P = 0.028, P = 0.046, respectively), while no significant association was found between serum lipid levels and HE location in CFP. CONCLUSIONS: MCI is superior to traditional CFP for the detection of HEs and the analysis of associations between HEs and serum lipid levels in DME.

11.
Zhen Ci Yan Jiu ; 46(3): 235-9, 2021 Mar 25.
Artículo en Chino | MEDLINE | ID: mdl-33798298

RESUMEN

OBJECTIVE: To explore the clinical effect of "Jin's three-needle" therapy and motor relearning regime for the recovery of upper limb motor function in the patients with ischemic stroke. METHODS: A total of 60 patients with ischemic stroke were randomly divided into an experiment group (30 cases) and a control group (30 cases). In the control group, the routine rehabilitation regimen was adopted. In the experimental group, on the base of the treatment regimen as the control group, the "Jin's three-needle" therapy was supplemented. The neurological function deficit score was used to assess the neurological function. The modified Fugel-Meyer assessment for upper extremities (FMA) and motor assessment scale (MAS) were adopted to assess the upper limb motor function in patients. The modified Barthel Index (MBI) was used to evaluate the activity of daily living (ADL) in patients. RESULTS: After treatment, the neurological function deficit score, the upper limb motor function (FMA and MAS) and ADL (MBI) were all improved obviously as compared with those before treatment (P<0.05). In the experimental group, the reducing range of neurological function deficit score (difference value) was larger than that in the control group (P<0.05). The increases of FMA score (upper arm function), the total score of MAS, the score for hand movement in MAS and the score for advanced hand activities of MAS, as well as MBI score in the experimental group were significantly larger than those in the control group successively (P<0.05). CONCLUSION: "Jin's three-needle" therapy combined with exercise relearning regimen effectively reduces the degree of neurological deficit and improve the upper limb motor function and ADL in patients with ischemic stroke.


Asunto(s)
Terapia por Acupuntura , Isquemia Encefálica , Rehabilitación de Accidente Cerebrovascular , Accidente Cerebrovascular , Isquemia Encefálica/tratamiento farmacológico , Humanos , Accidente Cerebrovascular/tratamiento farmacológico , Resultado del Tratamiento , Extremidad Superior
12.
Nat Commun ; 12(1): 1981, 2021 03 31.
Artículo en Inglés | MEDLINE | ID: mdl-33790287

RESUMEN

Histone acetylations are important epigenetic markers for transcriptional activation in response to metabolic changes and various stresses. Using the high-throughput SEquencing-Based Yeast replicative Lifespan screen method and the yeast knockout collection, we demonstrate that the HDA complex, a class-II histone deacetylase (HDAC), regulates aging through its target of acetylated H3K18 at storage carbohydrate genes. We find that, in addition to longer lifespan, disruption of HDA results in resistance to DNA damage and osmotic stresses. We show that these effects are due to increased promoter H3K18 acetylation and transcriptional activation in the trehalose metabolic pathway in the absence of HDA. Furthermore, we determine that the longevity effect of HDA is independent of the Cyc8-Tup1 repressor complex known to interact with HDA and coordinate transcriptional repression. Silencing the HDA homologs in C. elegans and Drosophila increases their lifespan and delays aging-associated physical declines in adult flies. Hence, we demonstrate that this HDAC controls an evolutionarily conserved longevity pathway.

13.
Cereb Cortex ; 2021 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-33822906

RESUMEN

Wnt/ß-catenin signaling plays multiple important roles during mammalian brain development, and it regulates the proliferation and differentiation of neural progenitors in a context-dependent manner and affects neocortex layer formation. However, the specific role of Wnt/ß-catenin in neuronal layer fate determination in the neocortex is still unclear. Here, we report that Zbed3, which is a positive regulator of Wnt/ß-catenin signaling, colocalizes with ß-catenin at the endfeet of radial glia in the ventricular zone of embryo mouse neocortex. Overexpression and knockdown of Zbed3 increased and decreased the activity of Wnt/ß-catenin signaling in the neocortex, respectively. Interestingly, knockdown of Zbed3 in vivo could significantly shift neuronal fates from deep layers to upper layers but is not required for the proliferation and differentiation of neural progenitors. Overexpression of Zbed3 led to increased generation of deep-layer neurons without impairing cell cycle exit of neural progenitors. More importantly, knockdown of Zbed3 could effectively block the effects of the ectopic expression of stabilized ß-catenin on neocortex layer formation. Hence, our results demonstrate that Zbed3 is indispensable for Wnt/ß-catenin signaling regulating neuronal layer fates in the developing brain.

14.
Zhongguo Yi Liao Qi Xie Za Zhi ; 45(2): 172-175, 2021 Apr 08.
Artículo en Chino | MEDLINE | ID: mdl-33825377

RESUMEN

For medical devices, there might have clinical differences in medical device efficacy and safety among different racial and ethnic subgroups. The acceptability of various data generated during the design and development stage of medical devices between different regions and national regulatory agencies faces huge challenges. This study discusses the considerations of racial and ethnic factors in the design and development of medical devices, with a view to improve the quality and availability of safety and effectiveness data under one framework.

15.
Pediatr Surg Int ; 2021 Apr 07.
Artículo en Inglés | MEDLINE | ID: mdl-33825955

RESUMEN

PURPOSE: Childhood obesity is a worsening epidemic. Little is known about the impact of overweight and obesity (OV-OB) on clinical outcomes after reduction for intussusception in children. The aim of this study was to compare clinical outcomes after primarily air enema reduction for intussusception in grouped OV-OB (body mass index-for-age percentile ≥ 85) pediatric patients compared with no OV-OB patients. METHODS: A retrospective study of 564 children who had undergone intussusception reduction via pneumatic reduction (PR) from April 2018 to January 2020 was conducted with assessments of demographic data, clinical symptoms, pre-reduction examination, and reduction results. One-to-one propensity score matching (PSM) was performed to compare clinical outcomes between patients with and without OV-OB, and the risk factors affecting recurrence and surgical reduction were analyzed in the PSM population. RESULTS: Of the 564 patients, 132 cases (23.4%) were OV-OB (overweight: 95 cases; obesity: 37 cases). In the propensity-matched analysis, the OV-OB group showed a significant increase in surgical reduction (10.2% versus 0.9%, P = 0.005) and recurrence (47.2% versus 10.2%, P < 0.001), excretion time of carbon powder after PR (median: 11.2 h versus 8.4 h, P < 0.001), higher maximum pressure of PR (median: 10.2 kPa versus 7.8 kPa, P < 0.001), and number of PR attempts (mean: 2.0 versus 1.4, P < 0.001). There were no significant differences in the reasons for surgery (PR failure or bowel perforation), time to recurrence (early or late), and the times of recurrences ≥ 2. After applying the multivariate logistic regression analysis, we found that OV-OB and white blood cell count ≥ 20 × 109/L were risk factors for both surgical reduction and the recurrence of intussusception. CONCLUSION: This study suggested that childhood OV-OB was associated with the failure of PR and recurrence of intussusception after reduction, which should be paid more attention in clinical practice.

16.
Int J Mol Sci ; 22(7)2021 Mar 31.
Artículo en Inglés | MEDLINE | ID: mdl-33807275

RESUMEN

High mobility group box 1 (HMGB1) has been demonstrated to promote the migration and invasion of non-small cell lung cancer (NSCLC). However, the mechanism of action of HMGB1 in regulating tumor mobility remains unclear. Therefore, we aimed to investigate whether HMGB1 affects mitochondria distribution and regulates dynamin-related protein 1 (DRP1)-mediated lamellipodia/filopodia formation to promote NSCLC migration. The regulation of mitochondrial membrane tension, dynamics, polarization, fission process, and cytoskeletal rearrangements in lung cancer cells by HMGB1 was analyzed using confocal microscopy. The HMGB1-mediated regulation of DRP1 phosphorylation and colocalization was determined using immunostaining and co-immunoprecipitation assays. The tumorigenic potential of HMGB1 was assessed in vivo and further confirmed using NSCLC patient samples. Our results showed that HMGB1 increased the polarity and mobility of cells (mainly by regulating the cytoskeletal system actin and microtubule dynamics and distribution), promoted the formation of lamellipodia/filopodia, and enhanced the expression and phosphorylation of DRP1 in both the nucleus and cytoplasm. In addition, HMGB1 and DRP1 expressions were positively correlated and exhibited poor prognosis and survival in patients with lung cancer. Collectively, HMGB1 plays a key role in the formation of lamellipodia and filopodia by regulating cytoskeleton dynamics and DRP1 expression to promote lung cancer migration.

17.
J Chemother ; : 1-7, 2021 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-33818318

RESUMEN

There is no standard treatment strategy for the third-line and above treatment of advanced nonsmall cell lung cancer (NSCLC). This study aimed to investigate the effects of anlotinib in patients with NSCLC. Data was collected from a group of advanced lung cancer patients who received anlotinib as a third-line or post-third-line treatment between 2017 and 2019. The Kaplan-Meier method was used to calculate the progression-free survival (PFS) of these lung cancer patients treated with anlotinib. Univariate analysis was performed using the log-rank test. Forest plot was used for subgroup analysis.Our study included 44 patients. Oral anlotinib was used as a third-line treatment to treat 26 patients, and as a fourth-line or multiline treatment in 18 patients. The objective control rate was 5%, the disease control rate was 89%, and the median PFS was 4.0 months with a 95% confidence interval. Common toxicities included anorexia, hypertension, and fatigue. Anlotinib demonstrated promising efficacy and was well tolerated with controlled toxicity in patients with NSCLC.

18.
Inorg Chem ; 2021 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-33793227

RESUMEN

Easily producible sensors for harmful industrial waste compounds are of significant interest for both human health and the environment. Three novel coordination polymers, [Ag(µ-aca)(µ4-bztpy)1/2] (1), [Ag(µ-bza)(µ-bpa)] (2), and [Ag2(µ-aca)2(µ-bpa)2]·EtOH·2H2O (3), were assembled in this study by reactions using Ag+ as a node with the pyridyl ligand 1,2,4,5-tetrakis(4-pyridyl)benzene (bztpy) or 9,10-bis(4-pyridyl)anthracene (bpa) and an auxiliary chelating carboxylic ligand. Single-crystal X-ray structural analyses revealed that compound 1 has a 3D framework consisting of 1D [Ag(aca)]∞ chains and bztpy linkers, while 2 and 3 have 2D layered structures consisting of binuclear Ag-carboxylate units and bpa linkers, respectively. Topological studies revealed that 1 has a bbf topology, while 2 and 3 are 2D [4,4] rhombic grids. The compounds were further characterized by powder X-ray diffraction, IR, elemental analysis, thermogravimetric analysis, and a luminescence study. The solids of 1-3 exhibited intense photoluminescent emission with λemmax at ca. 493, 472, and 500 nm, respectively. Remarkably, due to their excellent framework stability, 1 and 2 can act as multiresponsive luminescent sensors for nitrobenzene, Fe3+, and Cr2O72- with a high selectivity and sensitivity ascribed to their quenching effect.

19.
Mol Med ; 27(1): 27, 2021 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-33794764

RESUMEN

BACKGROUND: Growth factors execute essential biological functions and affect various physiological and pathological processes, including peripheral nerve repair and regeneration. Our previous sequencing data showed that the mRNA coding for betacellulin (Btc), an epidermal growth factor protein family member, was up-regulated in rat sciatic nerve segment after nerve injury, implying the potential involvement of Btc during peripheral nerve regeneration. METHODS: Expression of Btc was examined in Schwann cells by immunostaining. The function of Btc in regulating Schwann cells was investigated by transfecting cultured cells with siRNA segment against Btc or treating cells with Btc recombinant protein. The influence of Schwann cell-secreted Btc on neurons was determined using a co-culture assay. The in vivo effects of Btc on Schwann cell migration and axon elongation after rat sciatic nerve injury were further evaluated. RESULTS: Immunostaining images and ELISA outcomes indicated that Btc was present in and secreted by Schwann cells. Transwell migration and wound healing observations showed that transfection with siRNA against Btc impeded Schwann cell migration while application of exogenous Btc advanced Schwann cell migration. Besides the regulating effect on Schwann cell phenotype, Btc secreted by Schwann cells influenced neuron behavior and increased neurite length. In vivo evidence supported the promoting role of Btc in nerve regeneration after both rat sciatic nerve crush injury and transection injury. CONCLUSION: Our findings demonstrate the essential roles of Btc on Schwann cell migration and axon elongation and imply the potential application of Btc as a regenerative strategy for treating peripheral nerve injury.

20.
J Virol ; 2021 Mar 31.
Artículo en Inglés | MEDLINE | ID: mdl-33789998

RESUMEN

The COVID-19 pandemic poses a serious global health threat. The rapid global spread of SARS-CoV-2 highlights an urgent need to develop effective therapeutics for blocking SARS-CoV-2 infection and spread. Stimulator of Interferon Genes (STING) is a chief element in host antiviral defense pathways. In this study, we examined the impact of the STING signaling pathway on coronavirus infection using the HCoV-OC43 model. We found that HCoV-OC43 infection did not stimulate the STING signaling pathway, but the activation of STING signaling effectively inhibits HCoV-OC43 infection to a much greater extent than that of type I interferons (IFNs). We also discovered that IRF3, the key STING downstream innate immune effector, is essential for this anti-coronavirus activity. In addition, we found that the amidobenzimidazole (ABZI)-based human STING agonist (diABZI) robustly blocks the infection of not only HCoV-OC43 but also SARS-CoV-2. Therefore, our study identifies the STING signaling pathway as a potential therapeutic target that could be exploited for developing broad-spectrum antiviral therapeutics against multiple coronavirus strains in order to face the challenge of future coronavirus outbreaks.ImportanceThe highly infectious and lethal SARS-CoV-2 is posing an unprecedented threat to public health. Other coronaviruses are likely to jump from a non-human animal to humans in the future. Novel broad-spectrum antiviral therapeutics are therefore needed to control known pathogenic coronaviruses such as SARS-CoV-2 and its newly mutated variants, as well as future coronavirus outbreaks. STING signaling is a well-established host defense pathway, but its role in coronavirus infection remains unclear. In the present study, we found that activation of the STING signaling pathway robustly inhibits infection of HCoV-OC43 and SARS-CoV-2. These results identified the STING pathway as a novel target for controlling the spread of known pathogenic coronaviruses as well as emerging coronavirus outbreaks.

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