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1.
World J Clin Cases ; 12(19): 3800-3806, 2024 Jul 06.
Article in English | MEDLINE | ID: mdl-38994310

ABSTRACT

BACKGROUND: Hypocalcemia is highly common in hospitalized patients, especially in those with trauma, On the other hand, abnormal calcium metabolism is an important metabolic challenge; however, it is often neglected and untreated, and certain factors may induce serious neurological and cardiovascular complications. AIM: To retrospectively analyze the impact of hypocalcemia on the prognosis of patients with multiple traumas. METHODS: The study was conducted from January 2020 to December 2021. Ninety-nine patients with multiple injuries were treated at the critical care medicine department of Fuyang People's Hospital. The selected indicators included sex, age, and blood calcium and hematocrit levels. Many indicators were observed, including within 24 h of hospitalization, and the prognosis was collected after 28 d. Based on the blood calcium levels, the patients were divided into the following two groups: Normocalcemia and hypocalcemia. Of the 99 patients included, 81 had normocalcemia, and 18 had hypocalcemia. Separate experiments were conducted for these two groups. RESULTS: There was an association between serum calcium levels and the prognosis of patients with polytrauma. CONCLUSION: Clinically, the prognosis of patients with multiple traumas can be preliminarily evaluated based on serum calcium levels.

2.
PLoS One ; 19(4): e0296115, 2024.
Article in English | MEDLINE | ID: mdl-38568883

ABSTRACT

INTRODUCTION: Presbyopia, the leading cause of vision impairment globally, is common during working years. However, no trials have assessed presbyopia's impact on income. METHODS: In April 2017, we conducted a census among 59 Bangladesh villages to identify persons aged 35 to 65 years with presbyopia (presenting distance vision > = 6/12 bilaterally and correctable inability to see 6/13 at 40 cm with both eyes), who never had owned glasses. Participants were randomized (1:1) to receive immediate free reading glasses (intervention) or glasses delivered 8 months later (control). Visual demand of different jobs was stratified into three levels. Outcomes were between-group differences in the 8 month change in: self-reported monthly income (primary) and Near Vision Related Quality of Life (NVRQOL, secondary). RESULTS: Among 10,884 census participants, 3,655 (33.6%) met vision criteria and 863 (23.6%) comprised a sample enriched for near vision-intensive jobs, but 39 (4.52%) could not be reached. All participants allocated to intervention (n = 423, 51.3%) and control (n = 401, 48.7%) received the appropriate intervention, and follow-up was available for 93.4% and 96.8% respectively. Groups were similar at baseline in all characteristics: mean age was 47 years, 50% were male, 35% literate, and about half engaged in "most near vision-intensive" occupations. Glasses wear at 8-month follow-up was 88.3% and 7.81% in intervention and control respectively. At baseline, both the intervention and control groups had a self-reported median monthly income of US$35.3. At endline, the median income for the intervention group was US$47.1 compared with US$35.3 for control, a difference of 33.4%. Predictors of greater income increase in multivariate models included intervention group allocation (OR 1.45, 95% CI 1.12, 1.88, P = 0.005), male sex (OR 2.41, 95% CI 1.84, 3.16, P <0.001), and not engaging in income-producing work at baseline (OR 2.35, 95% CI 1.69, 3.26, P<0.001). CONCLUSION: Provision of reading glasses increases income in near vision-intensive occupations, and may facilitate return to work for those currently unemployed.


Subject(s)
Myopia , Presbyopia , Female , Humans , Male , Middle Aged , Bangladesh , Quality of Life , Vision, Ocular , Adult , Aged
3.
Materials (Basel) ; 16(18)2023 Sep 09.
Article in English | MEDLINE | ID: mdl-37763419

ABSTRACT

In the present paper, the dislocation-precipitate interaction in the Inconel 718 superalloy is studied by means of molecular dynamics simulation. The atomistic model composed of the ellipsoidal Ni3Nb precipitate (γ″ phase) and the Ni matrix is constructed, and tensile tests on the composite Ni3Nb@Ni system along different loading directions are simulated. The dislocation propagation behaviors in the precipitate interior and at the surface of the precipitate are characterized. The results indicate that the dislocation shearing and bypassing simultaneously occur during plastic deformation. The contact position of the dislocation on the surface of the precipitate could affect the penetration depth of the dislocation. The maximum obstacle size, allowing for the dislocation shearing on the slip planes, is found to be close to 20 nm. The investigation of anisotropic plastic deformation behavior shows that the composite system under the loading direction along the major axis of the precipitate experiences stronger shear strain localizations than that with the loading direction along the minor axis of the precipitate. The precipitate size effect is quantified, indicating that the larger the precipitate, the lower the elastic limit of the flow stress of the composite system. The dislocation accumulations in the precipitate are also examined with the dislocation densities given on specific slip systems. These findings provide atomistic insights into the mechanical behavior of nickel-based superalloys with nano-precipitates.

4.
Pain Ther ; 12(3): 671-682, 2023 Jun.
Article in English | MEDLINE | ID: mdl-36867364

ABSTRACT

INTRODUCTION: In clinical practice, cervical proprioception is usually evaluated by calculating the cervical joint position error (JPE) with laser pointer devices (LPD) or cervical range-of-motion (CROM) instruments. As technology continues to improve, more and more advanced tools are used to evaluate cervical proprioception. The purpose of this study was to analyze the reliability and validity of the WitMotion sensor (WS) device in evaluating cervical proprioception, and to explore a cheaper, more convenient, and more practical testing tool. METHODS: Twenty-eight healthy participants (16 women, 12 men; age 25-66 years) were recruited and evaluated for cervical joint position error with a WS and LPD by two independent observers. All participants repositioned their head to the target position and the deviation of repositioning was calculated using these two instruments. The intra- and inter-rater reliability of the instrument were determined by calculating the intraclass correlation coefficients (ICC), and the validity was analyzed by calculating the ICC and the Spearman's correlation. RESULTS: The intra-rater reliability of the WS (ICCs = 0.682-0.774) was higher than that of the LPD (ICCs = 0.512-0.719) for measuring JPE of cervical flexion, right lateral flexion, and left rotation. However, the LPD (ICCs = 0.767-0.796) outperformed the WS (ICCs = 0.507-0.661) in cervical extension, left lateral flexion, and right rotation. For the inter-rater reliability, the ICC values obtained by the WS and the LPD were above 0.70 for all cervical movements except cervical extension and left lateral flexion (ICCs = 0.580-0.679). For the validity, the ICC values were moderate to good (ICCs > 0.614) for measuring JPE in all movements with the WS and the LPD. CONCLUSIONS: Based on the high ICC values of reliability and validity, the novel device can be an alternative tool to evaluate cervical proprioception in clinical practice. TRIAL REGISTRATION: This study was registered in the Chinese Clinical Trial Registry (ChiCTR2100047228).

5.
Math Biosci Eng ; 18(5): 6527-6551, 2021 07 30.
Article in English | MEDLINE | ID: mdl-34517544

ABSTRACT

BACKGROUND: Previous studies revealed that the epithelial component is associated with the modulation of the ovarian tumor microenvironment (TME). However, the identification of key transcriptional signatures of laser capture microdissected human ovarian cancer epithelia remains lacking. METHODS: We identified the differentially expressed transcriptional signatures of human ovarian cancer epithelia by meta-analysis of GSE14407, GSE2765, GSE38666, GSE40595, and GSE54388. Then we investigated the enrichment of KEGG pathways that are associated with epithelia-derived transcriptomes. Finally, we investigated the correlation of key epithelia-hub genes with the survival prognosis and immune infiltrations. Finally, we investigated the genetic alterations of key prognostic hub genes and their diagnostic efficacy in ovarian cancer epithelia. RESULTS: We identified 1339 differentially expressed genes (DEGs) in ovarian cancer epithelia including 541upregulated and 798 downregulated genes. We identified 21 (such as E2F4, FOXM1, TFDP1, E2F1, and SIN3A) and 11 (such as JUN, DDX4, FOSL1, NOC2L, and HMGA1) master transcriptional regulators (MTRs) that are interacted with upregulated and the downregulated genes in ovarian tumor epithelium, respectively. The STRING-based analysis identified hub genes (such as CDK1, CCNB1, AURKA, CDC20, and CCNA2) in ovarian cancer epithelia. The significant clusters of identified hub genes are associated with the enrichment of KEGG pathways including cell cycle, DNA replication, cytokine-cytokine receptor interaction, pathways in cancer, and focal adhesion. The upregulation of SCNN1A and CDCA3 and the downregulation of SOX6 are correlated with a shorter survival prognosis in ovarian cancer (OV). The expression level of SOX6 is negatively correlated with immune score and positively correlated with tumor purity in OV. Moreover, SOX6 is negatively correlated with the infiltration of TILs, CD8+ T cells, CD4+ Regulatory T cells, cytolytic activity, T cell activation, pDC, neutrophils, and macrophages in OV. Also, SOX6 is negatively correlated with various immune markers including CD8A, PRF1, GZMA, GZMB, NKG7, CCL3, and CCL4, indicating the immune regulatory efficiency of SOX6 in the TME of OV. Furthermore, SCNN1A, CDCA3, and SOX6 genes are genetically altered in OV and the expression levels of SCNN1A and SOX6 genes showed diagnostic efficacy in ovarian cancer epithelia. CONCLUSIONS: The identified ovarian cancer epithelial-derived key transcriptional signatures are significantly correlated with survival prognosis and immune infiltrations, and may provide new insight into the diagnosis and treatment of epithelial ovarian cancer.


Subject(s)
Ovarian Neoplasms , Transcriptome , Carcinoma, Ovarian Epithelial/genetics , Computational Biology , Female , Gene Expression Regulation, Neoplastic , Humans , Ovarian Neoplasms/genetics , Tumor Microenvironment
6.
Aging (Albany NY) ; 13(12): 16445-16470, 2021 06 18.
Article in English | MEDLINE | ID: mdl-34148032

ABSTRACT

Acute myeloid leukemia (AML) is a group of heterogeneous hematological malignancies. We identified key genes as ITGAM and lncRNA ITGB2-AS1 through different bioinformatics tools. Furthermore, qPCR was performed to verify the expression level of essential genes in clinical samples. Retrospective research on 179 AML cases was used to investigate the relationship between the expression of ITGAM and the characteristics of AML. The critical gene relationship with immune infiltration in AML was estimated. The clinical validation and prognostic investigation showed that ITGAM, PPBP, and ITGB2-AS1 are highly expressed in AML (P < 0.001) and significantly associated with the overall survival in AML. Moreover, the retrospective research on 179 clinical cases showed that positive expression of ITGAM is substantially related to AML classification (P < 0.001), higher count of white blood cells (P < 0.01), and poor chemotherapy outcome (P < 0.05). Furthermore, based on grouping ITGAM as the high and low expression in TCGA-LAML profile, we found that genes in the highly expressed ITGAM group are mainly involved in immune infiltration and inflammation-related signaling pathways. Finally, we discovered that the expression level of ITGAM and lncRNA ITGB2-AS1 are not just closely related to the immune score and stromal score (P < 0.001) but also significantly positively correlated with various Immune signatures in AML (P < 0.001), indicating the association of these genes with immunosuppression in AML. The prediction of candidate drugs indicated that certain immunosuppressive drugs have potential therapeutic effects for AML. The critical genes could be used as potential biomarkers to evaluate the survival and prognosis of AML.


Subject(s)
Gene Expression Profiling , Gene Expression Regulation, Leukemic , Leukemia, Myeloid, Acute/genetics , Leukemia, Myeloid, Acute/immunology , Female , Gene Ontology , Gene Regulatory Networks , Genes, Essential , Humans , Leukemia, Myeloid, Acute/drug therapy , Male , Middle Aged , Prognosis , Protein Interaction Maps/genetics , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , ROC Curve , Reproducibility of Results , Signal Transduction/genetics , Transcriptome/genetics , Treatment Outcome , Tumor Microenvironment/genetics
7.
ACS Appl Mater Interfaces ; 12(40): 44789-44797, 2020 Oct 07.
Article in English | MEDLINE | ID: mdl-32910643

ABSTRACT

Metallic glasses (MGs) with superior catalytic performance have recently been recognized as attractive candidates for wastewater treatment. However, further improving their performance will require knowledge of how to precisely regulate their electronic structures via compositional control. Here, two Fe-based MGs (Fe78Si9B13 and Fe80Si9B11) were prepared to compare how slightly altering boron content affected their electronic structure and catalytic performance. Density functional theory revealed that the Fe78Si9B13 MG with 2 atom % higher boron exhibits an attractive electron delocalization, a high persulfate adsorption energy, and a superb work function due to precise regulation of the electronic structure, leading to exceptional degradation performance for seven organic pollutants. Furthermore, it can be reused 23 times without significant deterioration of catalytic performance, amorphous structure, and surface morphology. This work provides a new paradigm for the fundamental theory explaining how electronic structure is controlled by composition, creating a solid foundation to explore novel catalysts for water treatment.

8.
ACS Appl Mater Interfaces ; 12(27): 30584-30590, 2020 Jul 08.
Article in English | MEDLINE | ID: mdl-32538608

ABSTRACT

Understanding and controlling charge transport across multiple parallel molecules are fundamental to the creation of innovative functional electronic components, as future molecular devices will likely be multimolecular. The smallest possible molecular ensemble to address this challenge is a dual-molecule junction device, which has potential to unravel the effects of intermolecular crosstalk on electronic transport at the molecular level that cannot be elucidated using either conventional single-molecule or self-assembled monolayer (SAM) techniques. Herein, we demonstrate the fabrication of a scanning tunneling microscopy (STM) dual-molecule junction device, which utilizes noncovalent interactions and allows for direct comparison to the conventional STM single-molecule device. STM-break junction (BJ) measurements reveal a decrease in conductance of 10% per molecule from the dual-molecule to the single-molecule junction device. Quantum transport simulations indicate that this decrease is attributable to intermolecular crosstalk (i.e., intermolecular π-π interactions), with possible contributions from substrate-mediated coupling (i.e., molecule-electrode). This study provides the first experimental evidence to interpret intermolecular crosstalk in electronic transport at the STM-BJ level and translates the experimental observations into meaningful molecular information to enhance our fundamental knowledge of this subject matter. This approach is pertinent to the design and development of future multimolecular electronic components and also to other dual-molecular systems where such crosstalk is mediated by various noncovalent intermolecular interactions (e.g., electrostatic and hydrogen bonding).

9.
Sheng Li Xue Bao ; 72(2): 243-248, 2020 Apr 25.
Article in Chinese | MEDLINE | ID: mdl-32328618

ABSTRACT

Androgen plays an important role in singing of songbirds. Recent studies have shown that androgen levels in vivo not only affect the external morphology of songbirds, but also affect their singing behavior. Androgens (including derivatives) affect singing behavior and singing system in many ways. Based mainly on the results from our research group in the zebra finch, this review summarizes the effects of androgen on singing behavior, excitability and synaptic transmission of projection neurons of singing system, and the interaction of androgen with other neurotransmitter receptors in the brain of songbirds.


Subject(s)
Androgens/physiology , Brain/physiology , Songbirds/physiology , Vocalization, Animal , Animals
10.
J Cell Physiol ; 234(7): 11692-11707, 2019 07.
Article in English | MEDLINE | ID: mdl-30515795

ABSTRACT

Existing evidence has highlighted the effect of ultraviolet light radiation leading to corneal epithelium impairment. During this study, we aim to investigate the effect of microRNA-129-5p (miR-129-5p) on the wound healing process of corneal epithelial cells (CECs) induced by ultraviolet rays in mice by targeting epidermal growth factor receptor (EGFR). First, mouse models of ultraviolet ray-induced CEC injury were established and intrastromally injected with different mimic, inhibitor, and short interfering RNA (siRNA) to detect the effect of miR-129-5p on CEC injury. Subsequently, the corneal tissues were obtained to detect the antioxidant ability and EGFR-positive expression rate. The dual-luciferase reporter gene assay was used to test whether EGFR could directly target miR-129-5p. To further investigate the specific mechanism of miR-129-5p and EGFR in CEC injury, CECs were cultured and transfected with miR-129-5p mimic, miR-129-5p inhibitor, siRNA-EGFR, and miR-129-5p inhibitor + siRNA-EGFR. miR-129-5p has been proven to directly target EGFR. Inhibition of miR-129-5p is able to increase the antioxidant capacity, EGFR-positive rate and the expressions of EGFR, B-cell lymphoma-2, zonula occluden-1, occludin, and keratinocyte growth factor-2, but decrease the expression of vascular endothelial growth factor, BCL2-associated X protein, interleukin (IL)-1ß, and IL-4. Inhibition of miR-129-5p arrests cells at the S and G2 phases and decreases apoptosis. Our study provides evidence stating that inhibiting miR-129-5p and upregulating EGFR could aid in the repair of mice CEC injury induced by ultraviolet radiation. Therefore, inhibition of miR-129-5p might provide a basic theory in the repair of CEC injury caused by ultraviolet rays.


Subject(s)
Epithelial Cells/metabolism , Epithelial Cells/radiation effects , Epithelium, Corneal/injuries , ErbB Receptors/genetics , MicroRNAs/metabolism , Ultraviolet Rays , Up-Regulation/genetics , Animals , Antioxidants/metabolism , Apoptosis/genetics , Apoptosis/radiation effects , Base Sequence , Collagen/metabolism , Epithelial Cells/pathology , Epithelial Cells/ultrastructure , Epithelium, Corneal/pathology , Epithelium, Corneal/radiation effects , Epithelium, Corneal/ultrastructure , ErbB Receptors/metabolism , G1 Phase/genetics , G1 Phase/radiation effects , Luciferases/metabolism , Male , Malondialdehyde/metabolism , Mice, Inbred BALB C , MicroRNAs/genetics , Neovascularization, Pathologic/genetics , Occludin/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , Superoxide Dismutase/metabolism , Tight Junctions/metabolism , Tight Junctions/radiation effects , Up-Regulation/radiation effects , Zonula Occludens-1 Protein/metabolism
11.
J Nanosci Nanotechnol ; 18(8): 5502-5510, 2018 Aug 01.
Article in English | MEDLINE | ID: mdl-29458603

ABSTRACT

Elimination of pollutants from water is one of the greatest challenges in resolving global environmental issues. Herein, we report a high-surface-area mesoporous g-C3N4 nanosheet with remarkable high adsorption capacity and photocatalytic performance, which is prepared through directly polycondensation of urea followed by a consecutive one-step thermal exfoliation strategy. This one-pot method to prepare mesoporous g-C3N4 nanosheet is facile and rapid in comparison with others. The superior adsorption capacity of the fabricated mesoporous g-C3N4 nanostructures is demonstrated by a model organic pollutant-methylene blue (MB), which is up to 72.2 mg/g, about 6 times as that of the largest value of various g-C3N4 adsorbents reported so far. Moreover, this kind of porous g-C3N4 nanosheet exhibits high photocatalytic activity to MB and phenol degradation. Particularly, the regenerated samples show excellent performance of pollutant removal after consecutive adsorption/degradation cycles. Therefore, this mesoporous g-C3N4 nanosheet may be an attractive robust metal-free material with great promise for organic pollutant elimination.

12.
Sheng Li Xue Bao ; 69(4): 397-404, 2017 Aug 25.
Article in Chinese | MEDLINE | ID: mdl-28825097

ABSTRACT

Androgens can affect the singing behavior via regulating the song control system. In the present study, the effect of androgen on the synaptic plasticity of high vocal center (HVC)-robust nucleus of the arcopallium (RA) pathway was investigated through electrophysiological recording in vivo. We divided the adult male zebra finches into control, castration and castration plus testosterone implantation groups. The changes of long-term depression (LTD) and the paired-pulse facilitation in HVC-RA pathway induced by high-frequency (400 Hz, 2 s) stimulation of HVC were recorded, respectively. The results showed that high-frequency stimulation could effectively induce LTD in control group, but only evoke short-term depression in the castration group. In castration plus testosterone implantation group, LTD was restored. The paired-pulse facilitation was not obvious in the castration group, whereas it was significantly improved in the control and castration plus testosterone implantation groups. These results suggest that androgens may maintain the stability of song by influencing the level of LTD in HVC-RA pathway in adult male zebra finches, and androgens can affect the short-term synaptic plasticity of HVC-RA pathway.


Subject(s)
Androgens/physiology , Finches/physiology , High Vocal Center/physiology , Neuronal Plasticity , Animals , Electrophysiological Phenomena , Male , Testosterone , Vocalization, Animal
13.
Nan Fang Yi Ke Da Xue Xue Bao ; 36(7): 1008-13, 2016 Jun 20.
Article in Chinese | MEDLINE | ID: mdl-27435785

ABSTRACT

OBJECTIVE: To improve Luo-Ye pump-based stress-forming system and optimize the stimulating effect on smooth muscle cells during cultivation of tissue-engineered blood vessels (TEBV). METHODS: A new Luo-Ye pump-based TEBV 3D culture system was developed by adding an air pump to the output of the bioreactor. A pressure guide wire was used to measure the stress at different points of the silicone tube inside the TEBV bio-reactor, and fitting curves of the stress changes over time was created using Origin 8.0 software. The TEBVs were constructed by seeding vascular smooth muscle cells (VSMCs) isolated from human umbilical artery on polyglycolic acid (PGA) and cultured under dynamic conditions with 40 mmHg resistance (improved group), dynamic conditions without resistance (control group) or static condition (static group) for 4 weeks. The harvested TEBVs were then examined with HE staining, masson staining, α-SMA immunohistochemical staining, and scanning and transmission electron microscopy with semi-quantitative analysis of collagen content and α-SMA expression. RESULTS: The measured stress values and the fitting curves showed that the stress stimuli from the Luo-Ye pump were enhanced by adding an air pump to the output of the bioreactor. Histological analysis revealed improved VSMC density, collagen content and α-SMA expression in the TEBVs constructed with the improved method as compared with those in the control and static groups. CONCLUSION: Adding an air pump to the Luo-Ye pump significantly enhances the stress stimulation in the TEBV 3-D culture system to promote the secretion function of VSMCs.


Subject(s)
Bioreactors , Blood Vessel Prosthesis , Myocytes, Smooth Muscle/cytology , Tissue Engineering/methods , Cells, Cultured , Collagen/metabolism , Humans , Polyglycolic Acid
14.
PLoS One ; 11(7): e0158379, 2016.
Article in English | MEDLINE | ID: mdl-27383195

ABSTRACT

Targeting modules or signalings may open a new path to understanding the complex pharmacological mechanisms of reversing disease processes. However, determining how to quantify the structural alteration of these signalings or modules in pharmacological networks poses a great challenge towards realizing rational drug use in clinical medicine. Here, we explore a novel approach for dynamic comparative and quantitative analysis of the topological structural variation of modules in molecular networks, proposing the concept of allosteric modules (AMs). Based on the ischemic brain of mice, we optimize module distribution in different compound-dependent modular networks by using the minimum entropy criterion and then calculate the variation in similarity values of AMs under various conditions using a novel method of SimiNEF. The diverse pharmacological dynamic stereo-scrolls of AMs with functional gradient alteration, which consist of five types of AMs, may robustly deconstruct modular networks under the same ischemic conditions. The concept of AMs can not only integrate the responsive mechanisms of different compounds based on topological cascading variation but also obtain valuable structural information about disease and pharmacological networks beyond pathway analysis. We thereby provide a new systemic quantitative strategy for rationally determining pharmacological mechanisms of altered modular networks based on topological variation.


Subject(s)
Brain Ischemia , Brain/drug effects , Brain/physiology , Gene Expression Profiling , Allosteric Site , Animals , Brain Mapping , Chemistry, Pharmaceutical/methods , Gene Expression Regulation , Male , Mice , Models, Statistical , Signal Transduction , Tissue Array Analysis
15.
Neural Plast ; 2016: 7246827, 2016.
Article in English | MEDLINE | ID: mdl-26904300

ABSTRACT

Cholinergic mechanism is involved in motor behavior. In songbirds, the robust nucleus of the arcopallium (RA) is a song premotor nucleus in the pallium and receives cholinergic inputs from the basal forebrain. The activity of projection neurons in RA determines song motor behavior. Although many evidences suggest that cholinergic system is implicated in song production, the cholinergic modulation of RA is not clear until now. In the present study, the electrophysiological effects of carbachol, a nonselective cholinergic receptor agonist, were investigated on the RA projection neurons of adult male zebra finches through whole-cell patch-clamp techniques in vitro. Our results show that carbachol produced a significant decrease in the spontaneous and evoked action potential (AP) firing frequency of RA projection neurons, accompanying a hyperpolarization of the membrane potential, an increase in the evoked AP latency, afterhyperpolarization (AHP) peak amplitude, and AHP time to peak, and a decrease in the membrane input resistance, membrane time constant, and membrane capacitance. These results indicate that carbachol reduces the activity of RA projection neurons by hyperpolarizing the resting membrane potential and increasing the AHP and the membrane conductance, suggesting that the cholinergic modulation of RA may play an important role in song production.


Subject(s)
Carbachol/pharmacology , Cholinergic Agonists/pharmacology , Globus Pallidus/physiology , Neurons/physiology , Receptors, Cholinergic/physiology , Action Potentials/drug effects , Animals , Dose-Response Relationship, Drug , Finches , Globus Pallidus/drug effects , Male , Neural Pathways/drug effects , Neural Pathways/physiology , Neurons/drug effects
16.
Med Chem ; 12(4): 338-46, 2016.
Article in English | MEDLINE | ID: mdl-26548744

ABSTRACT

Hypoxia inducible factor-1 (HIF-1) is a key mediator during cancer cells to adapt tumor hypoxic condition. In this study, a series of adamantane-based compounds were synthesized and evaluated as potential inhibitors of HIF-1α. Examination of their structure-activity relationship (SAR) identified the adamantane-containing indole derivative 20a as a potent inhibitor of HIF-1α in Hep3B cell lines under tumor hypoxia (IC50 = 0.02 µM). The study herein may provide valuable information for the development of novel therapeutics against cancer and tumor angiogenesis.


Subject(s)
Acetanilides/pharmacology , Adamantane/analogs & derivatives , Adamantane/pharmacology , Antineoplastic Agents/pharmacology , Hypoxia-Inducible Factor 1, alpha Subunit/antagonists & inhibitors , Acetanilides/chemical synthesis , Acetanilides/toxicity , Adamantane/chemical synthesis , Adamantane/toxicity , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/toxicity , Cell Line, Tumor , Drug Screening Assays, Antitumor , Humans , Structure-Activity Relationship , Tumor Hypoxia
17.
World J Gastroenterol ; 21(5): 1488-97, 2015 Feb 07.
Article in English | MEDLINE | ID: mdl-25663768

ABSTRACT

AIM: To determine how the oncogene miR-21 regulates the RAS signaling pathways and affects colon cancer cell behaviors. METHODS: RAS p21 GTPase activating protein 1 (RASA1) protein expression in six colon cancer cell lines was assessed by Western blot. Colon cancer RKO cells were chosen for transfection because they are KRAS wild type colon cancer cells whose RASA1 expression is significantly decreased. RKO cells were transfected with vectors overexpressing or down-regulating either miR-21 or RASA1. Furthermore, a luciferase reporter assay was used to determine whether RASA1 is a gene target of miR-21. Then, changes in mRNA and protein levels of RASA1, RAS-GTP, and other components of the RAS signaling pathways were assessed in transfected RKO cells by real-time quantitative reverse transcription-polymerase chain reaction, Western blot and immunoprecipitation. Finally, cell proliferation, apoptosis, invasion, and tumor formation ability were assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide dye assay, flow cytometry, transwell assay, and animal experiment, respectively. RESULTS: RASA1 protein levels were significantly decreased in RKO cells compared with the other 5 colon cancer cell lines, and RASA1 was confirmed as a target gene of miR-21. Interestingly, RASA1 mRNA and protein levels in pre-miR-21-LV (up-regulation of miR-21) cells were lower than those in anti-miR-21-LV (down-regulation of miR-21) cells (P < 0.05). In addition, pre-miR-21-LV or siRASA1 (down-regulation of RASA1) cells showed higher cell proliferation, reduced apoptosis, increased expression of RAS-GTP, p-AKT, Raf-1, KRAS, and p-ERK1/2, and higher invasion and tumor formation ability, compared with control, anti-miR-21-LV or pcDNA3.1-RASA1 (up-regulation of RASA1) cells (P < 0.05). CONCLUSION: RASA1 is a target gene of miR-21, which promotes malignant behaviors of RKO cells through regulation of RASA1 expression.


Subject(s)
Colonic Neoplasms/metabolism , MicroRNAs/metabolism , Proto-Oncogene Proteins/metabolism , Signal Transduction , p120 GTPase Activating Protein/metabolism , ras Proteins/metabolism , Animals , Apoptosis , Caco-2 Cells , Cell Proliferation , Colonic Neoplasms/genetics , Colonic Neoplasms/pathology , Gene Expression Regulation, Neoplastic , HCT116 Cells , HT29 Cells , Humans , Male , Mice, Inbred BALB C , Mice, Nude , MicroRNAs/genetics , Proto-Oncogene Proteins/genetics , Proto-Oncogene Proteins p21(ras) , RNA, Messenger/metabolism , Time Factors , Transfection , Tumor Burden , p120 GTPase Activating Protein/genetics , ras Proteins/genetics
18.
Sheng Li Xue Bao ; 65(6): 586-92, 2013 Dec 25.
Article in Chinese | MEDLINE | ID: mdl-24343715

ABSTRACT

Long-term synaptic plasticity is considered as a key part of the neural mechanism of learning and memory. The production of learned vocalization of male zebra finches is closely related to high vocal center (HVC)-robust nucleus of the arcopallium (RA) pathway. However, the long-term plasticity of HVC-RA synapses is unclear. This study investigated the long-term plasticity of HVC-RA synapses in adult male zebra finches through in vivo field potential recording. The results showed that physiologic stimulation, i.e., δ rhythmic stimulation and low frequency stimulation could not effectively induce long-term synaptic plasticity. The former leaded to no change of the amplitudes of evoked population spikes, and the latter induced short-term depression (STD) of the amplitudes of the second evoked population spikes caused by paired pulses. But high frequency stimulation induced long-term depression (LTD) of the amplitudes of evoked population spikes to show out long-term synaptic plasticity. These results suggest that LTD represents the long-term plasticity of HVC-RA synapses in adult male zebra finches, which may be a key part of the neural mechanism of vocal learning and memory and can explain the plasticity of adult song to some degree.


Subject(s)
Finches/physiology , High Vocal Center/physiology , Neuronal Plasticity , Synapses/physiology , Animals , Evoked Potentials, Auditory , Learning , Male
19.
Hepatobiliary Pancreat Dis Int ; 12(2): 204-9, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23558076

ABSTRACT

BACKGROUND: KRAS mutation plays an important role in the pathogenesis of pancreatic cancer. However, the role of wild-type KRAS in the progression of pancreatic cancer remains unknown. The present study was to investigate the expression of the Ras GTPase activating protein (DAB2IP) in pancreatic cancer and its clinical significance. METHODS: The expression of DAB2IP in pancreatic cancer cell lines and normal human pancreatic ductal epithelial cells was analyzed by Western blotting and real-time quantitative reverse transcription-PCR (qRT-PCR). The KRAS mutational types of pancreatic cancer tissues obtained from pancreatic cancer patients (n=20) were also analyzed. Subsequently, DAB2IP expression was detected in pancreatic cancer tissues, adjacent and normal pancreatic tissues (n=2) by immunohistochemistry, and the relationship between DAB2IP expression and the clinical characteristics of patients was evaluated. RESULTS: Western blotting and qRT-PCR results showed that DAB2IP expression in pancreatic cancer cells with wild-type KRAS was lower than that in those with mutation-type KRAS and normal human pancreatic ductal epithelial cells (P<0.05). Immunohistochemistry showed that DAB2IP expression was lower in pancreatic cancer tissues than that in adjacent and normal pancreatic tissues (Z=-4.000, P=0.000). DAB2IP expression was lower in pancreatic cancer patients with the wild-type KRAS gene than that in those with KRAS mutations (WilcoxonW=35.000, P=0.042). Furthermore, DAB2IP expression in patients with perineurial invasion was lower than that in those without invasion (WilcoxonW=71.500, P=0.028). DAB2IP expression was lower in patients with more advanced stage than that in those with early clinical stage (WilcoxonW=54.000, P=0.002). CONCLUSIONS: DAB2IP expression was reduced in patients with pancreatic cancer compared with those with no cancer. DAB2IP expression was correlated with the KRAS gene, perineurial invasion and clinical stage of the disease. Our data indicated that DAP2IP expression can be used as a potential prognostic indicator and a promising molecular target for therapeutic intervention in patients with pancreatic cancer.


Subject(s)
Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Mutation , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/metabolism , Proto-Oncogene Proteins/genetics , ras GTPase-Activating Proteins/metabolism , ras Proteins/genetics , Adult , Aged , Analysis of Variance , Blotting, Western , Cell Line, Tumor , DNA Mutational Analysis , Down-Regulation , Female , Humans , Immunohistochemistry , Male , Middle Aged , Neoplasm Invasiveness , Neoplasm Staging , Pancreatic Neoplasms/pathology , Prognosis , Proto-Oncogene Proteins p21(ras) , Real-Time Polymerase Chain Reaction , Reverse Transcriptase Polymerase Chain Reaction , ras GTPase-Activating Proteins/genetics
20.
Dongwuxue Yanjiu ; 34(1): 1-7, 2013 Feb.
Article in Chinese | MEDLINE | ID: mdl-23389971

ABSTRACT

Learned vocalizations (long call and song) of adult male songbirds start from the high vocal center (HVC), and are integrated and output by the robust nucleus of the arcopallium (RA), which connects synaptic relationships with the dorsomedial nucleus of the intercollicular complex (DM). To determine the effect on learned vocalization of the unilateral forebrain and midbrain in adult male zebra finch, electrolytic lesions and acoustic analysis technology were used. The results indicated that RA and DM nuclei are involved in the control of learned vocalization, and the right side is dominant in the forebrain and midbrain.


Subject(s)
Finches/physiology , High Vocal Center/physiology , Mesencephalon/physiology , Prosencephalon/physiology , Vocalization, Animal/physiology , Animals , Brain Mapping , High Vocal Center/physiopathology , High Vocal Center/surgery , Learning/physiology , Male , Mesencephalon/physiopathology , Mesencephalon/surgery , Nerve Net/physiology , Nerve Net/physiopathology , Nerve Net/surgery , Neural Pathways/physiology , Neural Pathways/physiopathology , Prosencephalon/physiopathology , Prosencephalon/surgery , Sound Spectrography
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