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1.
Sci Total Environ ; 738: 139713, 2020 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-32526409

RESUMO

Esophageal cancer (EC) is a deadly malignancy worldwide with a high incidence and exhibits unevenly geographic prevalence, which suggests that environmental factors are deeply involved in the development of EC. Although the carcinogenesis of nitrosamines in the esophagus has been identified by tremendous toxicological data, the role of nitrosamines in the genesis of human EC has so far proved inconclusive largely due to a lack of convincing evidences. In this study, urinary nitrosamines in population controls and cases with esophageal precancerous lesions, including reflux esophagitis (RE) accompanying with basal cell hyperplasia (BCH) and dysplasia (DYS), and esophageal squamous cell carcinoma (ESCC) were detected by a SPE-LC-MS/MS method and the associated risk was evaluated. Higher excretion concentrations of N-nitrosomethylethylamine (NMEA) in the RE/BCH patients, NMEA and N-nitrosodibutylamine (NDBA) in the DYS patients, and NMEA, NDBA, N-nitrosopyrrolidine (NPyr) and N-nitrosomorpholine (NMor) in the ESCC patients were observed compared with the controls (p < .05). And with the progression of esophageal lesion, the exposure complexity increased in terms of the categories of nitrosamines. Furthermore, the observed positive associations between the hazardous exposure of NMEA, NDBA and NPyr and the increased risk of ESCC, and between NMEA and NDBA and RE/BCH were established. These findings provided direct evidence to support the hypothesis that exposure to nitrosamines are involved in the carcinogenesis of esophageal epithelia in this high incidence area from the perspective of endogenous exposure assessment. However, discoveries in this study need to be confirmed by systematic researches in the future. And the dose-response relationships, the reference ranges or cutoff values to predict the risks of nitrosamines exposure also need to be defined.

2.
Exp Neurol ; : 113391, 2020 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-32598930

RESUMO

Volume-regulated anion channels (VRACs) are critically involved in regulating cell volume, and leucine-rich repeat-containing protein 8A (LRRC8A, SWELL1) is an obligatory subunit of VRACs. Cell swelling occurs early after brain ischemia, but it is unclear whether neuronal LRRC8a contributes to ischemia-induced glutamate release and brain injury. We found that Lrrc8a conditional knockout (Lrrc8a-cKO) mice produced by crossing NestinCre+/- with Lrrc8aflox+/+ mice died 7-8 weeks of age, indicating an essential role of brain LRRC8A for survival. Middle cerebral artery occlusion (MCAO) caused an early increase in LRRC8A protein levels in the hippocampus in wild-type (WT) mice. Whole-cell patch-clamp recording in brain slices revealed that oxygen-glucose deprivation significantly increased the amplitude of VRAC currents in hippocampal CA1 neurons in WT but not in Lrrc8a-cKO mice. Hypotonicity increased the frequency of spontaneous excitatory postsynaptic currents (sEPSCs) in hippocampal CA1 neurons in WT mice, and this was abolished by DCPIB, a VRAC blocker. But in Lrrc8a-cKO mice, hypotonic solution had no effect on the frequency of sEPSCs in these neurons. Furthermore, the brain infarct volume and neurological severity score induced by MCAO were significantly lower in Lrrc8a-cKO mice than in WT mice. In addition, MCAO-induced increases in cleaved caspase-3 and calpain activity, two biochemical markers of neuronal apoptosis and death, in brain tissues were significantly attenuated in Lrrc8a-cKO mice compared with WT mice. These new findings indicate that cerebral ischemia increases neuronal LRRC8A-dependent VRAC activity and that VRACs contribute to increased glutamatergic input to hippocampal neurons and brain injury caused by ischemic stroke.

3.
Medicine (Baltimore) ; 99(21): e20390, 2020 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-32481339

RESUMO

RATIONALE: Fibrates are widely used to control hypertriglyceridemia and mixed dyslipidemia alone or in combination with statins. These drugs have rare, but severe and potentially vital adverse reactions of rhabdomyolysis and secondary acute renal failure (ARF). The objective of this article is to analyze this adverse effect of fibrates and ensure the safety of drug use. PATIENT CONCERNS: We report a case of rhabdomyolysis and ARF due to fenofibrate monotherapy in a 68-year-old female with post-pancreatitis diabetes mellitus and review reported cases of rhabdomyolysis correlated with fibrates monotherapy. DIAGNOSIS: The patient was diagnosed with rhabdomyolysis associated with fenofibrate monotherapy as confirmed by symptoms of fatigue and muscle pain, and elevated levels of myoglobin and creatine kinase. INTERVENTIONS: Fenofibrate therapy was discontinued. Moreover, intravenous fluids, urinary alkalization, and diuretic were performed. OUTCOMES: The symptoms were completely relieved, and relevant laboratory indexes returned to normal range during follow-up. LESSONS: Physicians should be aware of the side effect of rhabdomyolysis of fibrates, and patients should also be informed about this potential side effect, especially for patients with high-risk factors. A favorable outcome can be achieved by timely diagnosis and prompt treatment.


Assuntos
Fenofibrato/efeitos adversos , Hipertrigliceridemia/tratamento farmacológico , Rabdomiólise/etiologia , Idoso , Diabetes Mellitus/etiologia , Diabetes Mellitus/fisiopatologia , Feminino , Fenofibrato/uso terapêutico , Humanos , Hipertrigliceridemia/complicações , Pancreatite/complicações , Rabdomiólise/fisiopatologia
4.
Neuropharmacology ; 174: 108159, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32454125

RESUMO

The hypothalamic paraventricular nucleus (PVN) plays a major role in generating increased sympathetic output in hypertension. Although group III metabotropic glutamate receptors (mGluRs) are expressed in the hypothalamus, little is known about their contribution to regulating PVN presympathetic neurons in hypertension. Here we show that activating group III mGluRs with L-2-amino-4-phosphonobutyric acid (L-AP4) consistently inhibited the firing activity of spinally projecting PVN neurons in normotensive rats. However, in spontaneously hypertensive rats (SHRs), L-AP4 inhibited 45% of PVN neurons but excited 37%. L-AP4 significantly reduced glutamatergic and GABAergic input to PVN neurons in both groups. Blocking postsynaptic G protein signaling eliminated the excitatory but not the inhibitory effect of L-AP4 on PVN neurons in SHRs. Remarkably, prior activation of group I mGluRs converted the L-AP4 effect from inhibitory to excitatory in PVN neurons, and L-AP4 consistently inhibited PVN neurons when mGluR5 was blocked in SHRs. Furthermore, the expression level of mGluR4 and mGluR6 in the PVN was significantly higher in SHRs than in normotensive rats. Microinjection of L-AP4 into the PVN decreased blood pressure and lumbar sympathetic nerve discharges in normotensive rats and SHRs. Additionally, blocking group I mGluRs in the PVN potentiated L-AP4's sympathoinhibitory effect in SHRs. Therefore, activation of presynaptic group III mGluRs inhibits the excitability of PVN presympathetic neurons to attenuate sympathetic vasomotor activity. Through crosstalk with mGluR5, postsynaptic group III mGluR stimulation paradoxically excites PVN presympathetic neurons in SHRs. Concurrently blocking mGluR5 and activating group III mGluRs in the PVN can effectively reduce sympathetic outflow in hypertension.

5.
Zhongguo Yi Liao Qi Xie Za Zhi ; 44(2): 122-126, 2020 Feb 08.
Artigo em Chinês | MEDLINE | ID: mdl-32400984

RESUMO

EEG is a weak physiological electrical signal, which has important value in clinical and laboratory research. This paper mainly introduces several common methods of EEG signal processing, including power spectrum analysis, time-frequency analysis, bispectral analysis, etc, it mainly introduces their principles and applications in EEG signal processing, and provides methods and approaches for studying EEG.

6.
Microvasc Res ; 130: 104011, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32371104

RESUMO

To assess the microcirculation in a patient's capillaries, clinicians often use the valuable and non-invasive diagnostic tool of nailfold capillaroscopy (NC). In particular, evaluating the images that result from NC is particularly important for diagnosing diseases in which the capillary morphology is altered. However, NC images are generally of poor quality, such that analyzing them is difficult and time consuming. Thus, the purpose of this work was to determine a way to segment the capillaries in poor-quality NC images accurately. To do this, we proposed using a deep neural network with a Res-Unet structure. The network combines the residual network (ResNet) and the U-Net to establish an encoding-decoding network and to deepen the layers in the network to preserve the features of the deep layer. The network was trained on 30 nailfold capillary images to discriminate the pixels belonging to capillaries, and it was then tested on a dataset consisting of 20 images to achieve a binarized map. The mean accuracy was 91.72% and the mean Dice score was 97.66% compared to the ground truth, which indicates that using Res-Unet to perform capillary segmentation in NC images had good performance.

7.
Biol Reprod ; 103(1): 60-69, 2020 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-32301970

RESUMO

Wt1 gene encodes a nuclear transcription factor which is specifically expressed in ovarian granulosa cells and testicular Sertoli cells. Our previous studies demonstrated that Wt1 is required for the lineage specification of supporting cells and inactivation of Wt1 results in Sertoli cells to Leydig-like cells transformation. To test whether Wt1 is also involved in lineage maintenance of granulosa cells during ovary development, Wt1 was specifically deleted in pre-granulosa cells using Foxl2-cre. We found that the female Wt1-/flox; Foxl2-cre mice were infertile with atrophic ovaries and no growing follicles with multiple layers of granulosa cells were observed. A large number of 3ß-HSD-positive steroidogenic cells were detected in ovaries of Wt1-/flox; Foxl2-cre mice during embryonic stage and these cells were derived from Foxl2-expressing pre-granulosa cells. The quantitative results showed the expression of granulosa cell marker genes (Foxl2, Follistatin) was downregulated and steroidogenic cell marker genes (3ß-HSD, Cyp11a1, Star and Sf1) was dramatically increased in Wt1-/flox; Foxl2-cre ovaries. We also found that the meiosis of germ cells in Wt1-/flox; Foxl2-cre ovaries was delayed but not arrested. This study demonstrates that Wt1 is required for lineage maintenance of granulosa cells and inactivation of Wt1 results in pre-granulosa cells to steroidogenic cells transformation which in turn causes the defect of ovary development.

8.
Talanta ; 215: 120908, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32312452

RESUMO

Labile ferrous iron (Fe2+) plays important biochemical functions in many physiologically essential processes. It is very important to find an effective method to detect Fe2+. Herein, a simple and effective Fe2+ fluorescent probe (FeP1) has been constructed via a unique strategy of Fe2+-induced reducing reaction. As expected, FeP1 exhibited a 'turn-on' fluorescence response toward Fe2+ over various small analytes, with high selectivity and excellent sensitivity (DL = 18 nM) for the detection of Fe2+ in Tris-DMSO (4:1, pH = 7.4, v/v) solution. Moreover, the probe can act in different real samples, such as physiological saline and living cells.

9.
J Affect Disord ; 270: 118-123, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32339101

RESUMO

BACKGROUND: It has been demonstrated that a reduction in the amount of high-frequency cardiopulmonary coupling (CPC) is indicative of unstable sleep in unmedicated patients with major depressive disorder (MDD). Considering the close relationship between sleep quality and memory consolidation, this study sought to investigate the potential of high-frequency CPC as a novel biomarker for objective evaluation of memory impairment in MDD. METHODS: A total of 64 depressed patients and 35 healthy controls were included in this cross-sectional study. High-frequency coupling (HFC) was assessed by electrocardiogram-based CPC analysis using a portable sleep-respiration monitor during sleep for one night. The next day, subjects completed the cognition assessment with the Assessment of Neuropsychological Status (RBANS). The 17-Item Hamilton Depression Rating Scale (HAMD17) and the Hamilton Rating Scales for Anxiety (HAMA) were used to evaluate the severity of depression and anxiety in each patient, respectively. RESULTS: There was no significant difference in the proportion of HFC between depressed patients and healthy controls. In patients with low HFC proportion (<35%), severe anxiety could significantly decrease HFC proportion. The HFC proportion positively correlated with immediate and delayed memory in depressed patients. Further analysis showed that patients with low HFC proportion may have worse delayed memory. LIMITATIONS: The lack of prior exposure to the monitoring equipment and procedure could have generated artefacts that would have disappeared after habituation. CONCLUSIONS: These results support a positive correlation between the HFC proportion and memory in depressed patients. Further research is required to explore the clinical implications of these findings.

10.
Wei Sheng Yan Jiu ; 49(1): 98-131, 2020 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-32290922

RESUMO

OBJECTIVE: To study the effect of curcumin on the expression of glucose regulated protein 78 kD(GRP78) and cysteinyl aspartate specific proteinase-12(caspase-12) of myocardial endoplasmic reticulum stress related factors in type 2 diabetes rats. METHODS: Type 2 diabetes rats model was established by high-fat drink feeding and one-time intraperitoneal injecting streptozotocin(35 mg/kg). After model rats were built, rats was randomly divided into diabetic model group and low dose of curcumin group(200 mg/kg), high dose of curcumin group(400 mg/kg) and captopril group(60 mg/kg) with 10 rats in each group. The rats in each group were ig administered with corresponding drugs once a day. Continuous administration for 12 w. The levels of fasting blood glucose(FBG) and lactate dehydrogenase(LDH), electrocardiogram and heart weight index(HWI) were measured respectively. The myocardial pathological changes were observed by HE staining. The levels of collagen fiber expression in myocardial tissue were performed by Masson staining. The protein expression levels of GRP78 and caspase-12 in myocardium of rats were observed by immunohistochemistry. RESULTS: The result showed that compared with control group, the levels of FBG and LDH of serum were increased obviously, HWI was increased, myocardial cells were hypertrophy, the collagen fibers of intercellular space of cell were increased, the protein expressions of GRP78 and caspase-12 of myocardium were increased in rats, myocardial cell apoptosis was increased in the model group(P<0. 05). Compared with model group, FBG and LDH levels and HWI were reduced, the collagen fiber of intercellular space were decreased, the protein expression levels of GRP78 and caspase-12 were lowered in high dose of curcumin group(P<0. 05). CONCLUSION: It indicates that Cur defends myocardium tissue in type 2 diabetes rats, which may be related to decreasing the level of blood glucose and the protein expressions of GRP78 and caspase-12, and blocking the ERS-initiated apoptotic.

11.
Genes (Basel) ; 11(3)2020 03 07.
Artigo em Inglês | MEDLINE | ID: mdl-32156087

RESUMO

Methyl-CpG-binding domain (MBD) proteins have diverse molecular and biological functions in plants. Most studies of MBD proteins in plants have focused on the model plant Arabidopsis thaliana L. Here we cloned SvMBD5 from the willow Salix viminalis L. by reverse transcription-polymerase chain reaction (RT-PCR) and analyzed the structure of SvMBD5 and its evolutionary relationships with proteins in other species. The coding sequence of SvMBD5 is 645 bp long, encoding a 214 amino acid protein with a methyl-CpG-binding domain. SvMBD5 belongs to the same subfamily as AtMBD5 and AtMBD6 from Arabidopsis. Subcellular localization analysis showed that SvMBD5 is only expressed in the nucleus. We transformed Arabidopsis plants with a 35S::SvMBD5 expression construct to examine SvMBD5 function. The Arabidopsis SvMBD5-expressing line flowered earlier than the wild type. In the transgenic plants, the expression of FLOWERING LOCUS T and CONSTANS significantly increased, while the expression of FLOWERING LOCUS C greatly decreased. In addition, heterologously expressing SvMBD5 in Arabidopsis significantly inhibited the establishment and maintenance of methylation of CHROMOMETHYLASE 3 and METHYLTRANSFERASE 1, as well as their expression, and significantly increased the expression of the demethylation-related genes REPRESSOR OF SILENCING1 and DEMETER-LIKE PROTEIN3. Our findings suggest that SvMBD5 participates in the flowering process by regulating the methylation levels of flowering genes, laying the foundation for further studying the role of SvMBD5 in regulating DNA demethylation.

12.
Bioorg Med Chem ; 28(9): 115438, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32199689

RESUMO

Endomorphin (EM)-1 and EM-2 are the most effective endogenous analgesics with efficient separation of analgesia from the risk of adverse effects. Poor metabolic stability and ineffective analgesia after peripheral administration were detrimental for the use of EMs as novel clinical analgesics. Therefore, here, we aimed to establish new EM analogs via introducing different bifunctional d-amino acids at position 2 of [(2-furyl)Map4]EMs. The combination of [(2-furyl)Map4]EMs with D-Arg2 or D-Cit2 yielded analogs with enhanced binding affinity to the µ-opioid receptor (MOR) and increased stability against enzymatic degradation (t1/2 > 300 min). However, the agonistic activities of these analogs toward MOR were slightly reduced. Similar to morphine, peripheral administration of the analog [D-Cit2, (2-furyl)Map4]EM-1 (10) significantly inhibited the pain behavior of mice in multiple pain models. In addition, this EM-1 analog was associated with reduced tolerance, less effect on gastrointestinal mobility, and no significant motor impairment. Compared to natural EMs, the EM analogs synthesized herein had enhanced metabolic stability, bioavailability, and analgesic properties.

13.
Int J Mol Med ; 45(2): 623-633, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31894313

RESUMO

The objective of the present study was to investigate the molecular mechanism underlying the role of metformin (Met) in reducing the risk of endometrial hyperplasia (EH). Reverse transcription­quantitative polymerase chain reaction, western blot and immunohistochemistry (IHC) assays were used to study the effects of Met and tamoxifen on the expression levels of urothelial cancer associated 1 (UCA1), microRNA­144 (miR­144) and other factors along the transforming growth factor­ß1 (TGF­ß1)/protein kinase B (AKT) signaling pathway. In addition, MTT and flow cytometry assays were performed to detect the effect of Met on cell proliferation and apoptosis. Tamoxifen treatment increased the weight of the uterus and the level of UCA1, while decreasing the expression of miR­144. In addition, treatment with tamoxifen (2.0 and 3.5 µg) upregulated the protein expression levels of TGF­ß and p­AKT, while downregulating the protein expression of active Caspase­3 in a dose­dependent manner. By contrast, Met reduced cell viability, promoted cell apoptosis, and reduced the expression levels of UCA1, TGF­ß and p­AKT, while upregulating the expression of miR­144 and active Caspase­3 in a dose­dependent manner. Furthermore, Met also reduced the weight of uterus. However, tamoxifen and Met did not exert any effect on the protein levels of total AKT and total Caspase­3. The levels of TGF­ß and p­AKT proteins in the EH group were much higher when compared with those in the sham group, while Met treatment reduced these protein levels to a certain extent. In addition, the expression of active Caspase­3 in the EH group was much lower than that in the sham group, while Met treatment increased its level to a certain extent. In conclusion, the current study suggested that Met reduces the risk of EH by reducing the expression levels of UCA1, TGF­ß and p­AKT, while increasing the levels of miR­144 and active Caspase­3 in a dose­dependent manner.

14.
Psychol Med ; : 1-9, 2020 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-31931894

RESUMO

BACKGROUND: This study aimed to examine the efficacy of combining paroxetine and mirtazapine v. switching to mirtazapine, for patients with major depressive disorder (MDD) who have had an insufficient response to SSRI monotherapy (paroxetine) after the first 2 weeks of treatment. METHODS: This double-blind, randomized, placebo-controlled, three-arm study recruited participants from five hospitals in China. Eligible participants were aged 18-60 years with MDD of at least moderate severity. Participants received paroxetine during a 2-week open-label phase and patients who had not achieved early improvement were randomized to paroxetine, mirtazapine or paroxetine combined with mirtazapine for 6 weeks. The primary outcome was improvement on the Hamilton Rating Scale for Depression 17-item (HAMD-17) scores 6 weeks after randomization. RESULTS: A total of 204 patients who showed early non-response to paroxetine monotherapy were randomly assigned to receive either mirtazapine and placebo (n = 68), paroxetine and placebo (n = 68) or mirtazapine and paroxetine (n = 68), with 164 patients completing the outcome assessment. At week 8, the least squares (LS) mean change of HAMD-17 scores did not significantly differ among the three groups, (12.98 points) in the mirtazapine group, (12.50 points) in the paroxetine group and (13.27 points) in the mirtazapine plus paroxetine combination group. Participants in the paroxetine monotherapy group were least likely to experience adverse effects. CONCLUSIONS: After 8 weeks follow-up, paroxetine monotherapy, mirtazapine monotherapy and paroxetine/mirtazapine combination therapy were equally effective in non-improvers at 2 weeks. The results of this trial do not support a recommendation to routinely offer additional treatment or a switch in treatment strategies for MDD patients who do not show early improvement after 2 weeks of antidepressant treatment.

15.
Asian J Psychiatr ; 47: 101843, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31731143

RESUMO

AIMS & OBJECTIVES: Age differences exist in many aspects in patients with major depressive disorder (MDD). The present study aims to examine the effect of age on treatment outcomes in first-episode MDD. METHODOLOGY: A total of 982 first-episode major depressive patients, who were above 18 years old and admitted in both psychiatric hospitals and units of general hospitals were recruited for the present study. These patients were newly treated and responded to 8-12 weeks of antidepressant treatment. Depressive symptoms, psychosocial functioning and quality of life were measured using standardized instruments. The study population was divided into three age groups: early adult (18-44 years old), middle adult (45-59 years old), and late adult (60-85 years old). RESULTS: Earlier age was associated with greater symptom severity, severer depressive symptoms in hypersomnia, concentration/decision making, negative view of the self, suicide ideation and restlessness, more impaired function, poorer satisfaction in social relationship and economic status, when compared to late adults with MDD (all P < 0.05). In the multivariable analyses, among the other variables, early age remained as an independent correlation of residual depressive severity (middle age vs. early age: OR = 0.631, 95%CI[0.462, 0.862]; old age vs. early age: OR = 0.521, 95%CI[0.348, 0.780]) and functional impairment. Comorbidity of physical illness had a negative contribution to all treatment outcomes. CONCLUSION: In first major depressive episode, early age was strongly associated with depressive severity and functional impairment after responding to antidepressant treatment. Early-life depression may be an indicator of MDD for poor clinical outcomes and high clinical burden.

16.
J Sep Sci ; 43(5): 996-1002, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31837090

RESUMO

Bovine serum albumin imprinted magnetic microspheres, with functional monomers of modified chitosan, N-isopropylacrylamide and sulfobetaine methacrylate, were successfully prepared and characterized in detail. Computational analyses showed that during the preparation process, modified chitosan can effortlessly form multiple non-covalent bonds with protein molecules. Temperature-sensitive N-isopropylacrylamide improves the elution efficiency by abating the mass transfer resistance. Meanwhile, the zwitterionic sulfobetaine methacrylate strongly interacts with H2 O molecules, remarkably reducing the non-specific adsorption. The specific bovine serum albumin adsorption performances of the prepared imprinted material were then determined. The adsorption amount reached 86.87 mg/g and the imprinting factor was 6.49. These excellent specific adsorption properties are attributed to the synergetic effects of the different monomers. The fabricated imprinted material not only exhibits great prospects as a biosensor or separation material for protein molecules, but also provides a collaborative strategy for preparing multi-functional imprinted materials.

17.
BMC Cancer ; 19(1): 1067, 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31703640

RESUMO

BACKGROUND: In past decades, circular RNAs (circRNAs) have achieved increasing attention because of its regulatory role in different kinds of cancers. However, how circAGFG1 regulates cervical cancer (CC) is still largely undiscovered. This study aims to evaluate the role of a novel circRNAs and related molecular mechanism in CC cells. METHODS: High or low level of circAGFG1 was detected in CC cells or normal cell line with qRT-PCR. The proliferative and migratory abilities of CC cells were assessed with loss-of function assays. The downstream miRNA and mRNA of circAGFG1 were searched out and proved by using bioinformatics analysis and mechanism experiments. Recue assays were designed to confirm the role of circAGFG1/miR-370-3p/RAF1 axis in CC cell activities. RESULTS: The levels of circAGFG1 was abundant in CC cells in comparison with normal cervical cell End1/E6E7. The inhibitory effect of decreased circAGFG1 level on the proliferative and migratory abilities of CC cells was assessed. CircAGFG1 and miR-370-3p were localized in the cytoplasm and they can interact with each other. Moreover, miR-370-3p was downregulated in CC cells. We also determined the negative effect of miR-370-3p on RAF1. CircAGFG1 could promote RAF1 expression by absorbing miR-370-3p, thereby activating RAF/MEK/ERK pathway. circAGFG1 promoted proliferation and migration of CC cells via enhancing the activity of RAF/MEK/ERK pathway by sponging miR-370-3p and further regulating RAF1. CONCLUSION: The results of this study provided new evidence that circAGFG1 acted as a vital regulator in cervical cancer proliferation and migration, giving great promise to apply it as a potential biomarker for diagnosis and therapy in CC treatment.


Assuntos
MicroRNAs/metabolismo , Complexo de Proteínas Formadoras de Poros Nucleares/genética , Proteínas Proto-Oncogênicas c-raf/metabolismo , RNA Circular/genética , Proteínas de Ligação a RNA/genética , Neoplasias do Colo do Útero/metabolismo , Movimento Celular/genética , Proliferação de Células/genética , Sobrevivência Celular/genética , Progressão da Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Inativação Gênica , Células HeLa , Humanos , Complexo de Proteínas Formadoras de Poros Nucleares/metabolismo , RNA Circular/metabolismo , Proteínas de Ligação a RNA/metabolismo , Transdução de Sinais/genética , Transfecção , Neoplasias do Colo do Útero/genética
18.
Mol Med Rep ; 20(5): 4540-4550, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31702035

RESUMO

Rheumatoid arthritis (RA) is characterized by chronic inflammatory synovitis resulting in progressive joint destruction. Persistent synovial inflammation is induced by activation of various inflammatory cells. G­protein­coupled bile acid receptor 1 (TGR5) is a G­protein­coupled receptor activated by various bile acids, which has been reported to act as a key adaptor in regulating various signaling pathways involved in inflammatory responses and a diverse array of physiological processes, including bile acid synthesis, lipid and carbohydrate metabolism, carcinogenesis, immunity and inflammation. In the present study, TGR5 expression was detected in RA peripheral blood mononuclear cells (PBMCs), and its association with clinical disease activity, histological synovitis severity and radiological joint destruction was analyzed. Subsequently, the role and potential underlying mechanisms of TGR5 in the PBMCs of patients with RA and mice with collagen II­induced arthritis (CIA) were investigated. PBMCs were obtained from 50 patients with RA and 40 healthy controls (HCs). The mRNA and protein expression levels of TGR5 were detected in PBMCs via reverse transcription­quantitative polymerase chain reaction (RT­qPCR) and immunofluorescence staining, respectively. Additionally, the levels of proinflammatory cytokines were analyzed by RT­qPCR and enzyme­linked immunosorbent assay (ELISA). The activation of nuclear factor­κB (NF­κB) and IκB kinase a was determined via western blot analysis. The anti­arthritic and anti­inflammatory effects of LCA on mice with CIA were then investigated. The arthritis score was assessed, and the protein levels of proinflammatory cytokines in the plasma of mice were detected via ELISA. TGR5 mRNA expression was significantly downregulated in the PBMCs of patients with RA compared with in those of the HCs (0.53±0.58 for patients vs. 1.49±0.83 for HCs; P<0.001); similar findings were observed at the protein level. The mRNA expression levels of TGR5 in the PBMCs of patients with RA with a high 28­Joint Disease Activity Score (DAS28) were significantly decreased compared with in patients with a low DAS28 (0.81±0.65 for low score vs. 0.35±0.46 for high score; P=0.002). Furthermore, TGR5 expression was significantly correlated with the levels of C­reactive protein (r=­0.429; P=0.002) and the DAS28 (r=­0.383; P=0.006). RT­qPCR and ELISA analyses indicated that lithocholic acid (LCA, 10 mg/kg/day) attenuated lipopolysaccharide­induced proinflammatory cytokine production via inhibition of NF­κB activity in the PBMCs of patients with RA. In addition, the arthritis score was significantly decreased in LCA­treated CIA mice compared with in non­treated CIA mice. The increased production of tumor necrosis factor­α, interleukin (IL)­1ß, IL­6 and IL­8 was significantly reduced in the plasma of LCA­treated CIA mice compared with the control. In conclusion, TGR5 may contribute to the inflammation of PBMCs in patients with RA and mice with CIA.


Assuntos
Artrite Experimental/metabolismo , Artrite Reumatoide/metabolismo , Regulação da Expressão Gênica , Leucócitos Mononucleares/metabolismo , Receptores Acoplados a Proteínas-G/biossíntese , Tiorredoxina Dissulfeto Redutase/biossíntese , Animais , Artrite Experimental/patologia , Artrite Reumatoide/patologia , Citocinas/metabolismo , Feminino , Humanos , Inflamação/metabolismo , Inflamação/patologia , Leucócitos Mononucleares/patologia , Masculino , Camundongos , Pessoa de Meia-Idade
19.
Gen Physiol Biophys ; 38(5): 407-416, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31595882

RESUMO

The P2X7 receptor (P2X7R) plays an important role in inflammatory and neuropathic pain. Our recent study indicated that activation of P2X7R in microglial cells of spinal cord contributes to the inflammatory pain induced by BmK I, the major active compound from Buthus martensi Karsch (BmK). In the present study, we further investigated whether P2X7R in satellite glial cells (SGCs) of dorsal root ganglion (DRG) is involved in the BmK I-induced pain in rats. The results found that the expression of P2X7R in SGCs was increased in the ipsilateral side of L4-L5 DRGs after intraplantar injection of BmK I. Moreover, the expression of an inflammatory cytokine IL-1ß was increased in DRG after BmK I injection. Systemic administration of an inhibitor of P2X7R (A-438079) significantly inhibited both spontaneous and evoked nociceptive behaviors induced by BmK I. These results suggest that the P2X7R in SGCs of DRG might contribute to pain induced by toxins that sensitize peripheral sensory nerves.


Assuntos
Gânglios Espinais/patologia , Dor/induzido quimicamente , Dor/patologia , Receptores Purinérgicos P2X7/metabolismo , Células Satélites Perineuronais/metabolismo , Venenos de Escorpião , Animais , Dor/metabolismo , Ratos
20.
Oxid Med Cell Longev ; 2019: 8030697, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31583044

RESUMO

The interaction between germ cell and somatic cell plays important roles in germ cell development. However, the exact function of gonad somatic cell in germ cell differentiation is unclear. In the present study, the function of gonad somatic cell in germ cell meiosis was examined by using mouse models with aberrant somatic cell differentiation. In Wt1R394W/R394W mice, the genital ridge is absent due to the apoptosis of coelomic epithelial cells. Interestingly, in both male and female Wt1R394W/R394W germ cells, STRA8 was detected at E12.5 and the scattered SYCP3 foci were observed at E13.5 which was consistent with control females. In Wt1-/flox; Cre-ERTM mice, Wt1 was inactivated by the injection of tamoxifen at E9.5 and the differentiation of Sertoli and granulosa cells was completely blocked. We found that most germ cells were located outside of genital ridge after Wt1 inactivation. STRA8, SYCP3, and γH2AX proteins were detected in germ cells of both male and female Wt1-/flox; Cre-ERTM gonads, whereas no thread-like SYCP3 signal was observed. Our study demonstrates that aberrant development of gonad somatic cells leads to ectopic expression of meiosis-associated genes in germ cells, but meiosis was arrested before prophase I. These results suggest that the proper differentiation of gonad somatic cells is essential for germ cell meiosis.


Assuntos
Células Germinativas/metabolismo , Animais , Diferenciação Celular , Feminino , Gônadas , Células Híbridas , Masculino , Meiose , Camundongos
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